In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of...In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.展开更多
Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of d...Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF<sup>+</sup>/Fzd4<sup>+</sup> cells in the hair follicle were significantly decreased in number in the lesions, Nestin<sup>+</sup> and p75NGFR<sup>+</sup> cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.展开更多
Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simp...Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simple technique by direct melanocytes transplant by spade needle technique in treatment of vitiligo. Patients and Methods: This interventional, therapeutic, comparative study was done in Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from April 2014-March 2015. Twenty patients with localized, generalized and segmental vitiligo were included. Full history and examination for each patient was done with 4 (20%) males and 16 (80%) females and their ages ranged from 9 - 40 (23.15 ± 11.44) years. Forty one patches in 20 patients treated by spade grafting technique and the donor and recipient sites were demarcated and anesthesia done by xylocaine 2% with adrenalin 1:100,000. Transplantation was started by using disposable needle gauge 18 (the sharp end of needle was cut by a scissor to make it a spade like) with medical syringe 5 ml supplied with normal saline. The micro-pieces were taken from donor site and transplanted directly, easily and rapidly into dermis of recipient site and followed by pushing normal saline and the procedure was repeated to cover all recipient sites with 5 mm distance between injection points. The surface area of the lesions was calculated and the reduction rate was estimated every month till the end of the 4th month period of the treatment. Results: Including 41 patches in 20 patients with the surface area of the patches ranged from 1.5 - 90 cm<sup>2</sup> (13.78 ± 17.57) cm<sup>2</sup>. The mean ±SD of surface area of lesions was decreased from 13.78 ± 17.57 cm<sup>2</sup> at baseline visit to 13.61 ± 17.48 cm<sup>2</sup> at the second visit (after 2 weeks ) which was statistically significant (p value ≤ 0.001). The mean surface area continued to be reduced till reaching 12.20 ± 15.68 cm<sup>2</sup> at the third visit and 12.01 ± 15.55 cm<sup>2</sup> at the fourth visit. All were statistically significant when compared to baseline visit. There was reduction in surface area 1.1% at two weeks, 9.93%, and 12.5% at the 2nd, 4th months respectively. Conclusions: Intradermal injection of melanocytes in patients with vitiligo by spade like needle was very quick and simple non-costly technique, and gave 12.5% reduction which could be repeated at different times until satisfactory re-pigmentation of vitiligenous skin is achieved.展开更多
Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from t...Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.展开更多
Keishibukuryogankayokuinin (KBY) is a traditional Japanese herbal medicine widely used to treat skin pigmentation. The scientific basis for its use is, however, unclear, and studies evaluating its mechanism and effect...Keishibukuryogankayokuinin (KBY) is a traditional Japanese herbal medicine widely used to treat skin pigmentation. The scientific basis for its use is, however, unclear, and studies evaluating its mechanism and effectiveness are sparse. In this study, we compared the tyrosinase inhibitory effects of KBY and Keishibukuryogan (KB, which has the same composition of KBY, except Coix Seed [CS]) and CS under exposure to UV radiation as well as under non-exposure conditions. Neonatal human epidermal melanocytes obtained from a darkly pigmented donor were used. These cells were cultured in a final concentration of 500 μg/ml or 1000 μg/ml, to which KBY, KB, and CS were added. After incubation for 72 h, cells were stained with Fontana-Masson stain and counted. Tyrosinase activity was measured by its dopa oxidase activity, and tyrosinase expression was estimated using real-time PCR. For UV radiation, cells were exposed to UVB radiation for 90 s per day for 3 days. Under non-exposure conditions, tyrosinase activity significantly increased with both KBY and KB but significantly decreased with CS, regardless of the concentration. In addition, tyrosinase expression significantly decreased but only with KBY at both concentrations. Under UV radiation exposure, tyrosinase activity significantly increased with KBY and KB at both concentrations while tyrosinase expression significantly decreased with KBY and KB;a significant increase was, however, observed with CS at both concentrations. These results suggest that taking KBY after sunburn is effective against skin pigmentation, and the combination of KB and CS is useful for skin depigmentation.展开更多
Objective To elucidate the effect of Ge 132 on the growth of melanocytes.Methods Melanocyes from epidermis were cultured and purified;the second generation of the cell was used for study;the cells were divided into tw...Objective To elucidate the effect of Ge 132 on the growth of melanocytes.Methods Melanocyes from epidermis were cultured and purified;the second generation of the cell was used for study;the cells were divided into two groups randomly,to group A, Ge 132 was added to the media at 0.04mg/L;to group B,common culturing method was used without Ge 132.After 5d, the cells were seperated by digestion for study by transmission electronic microscope.Results Compared to group B, the vaculoes of the cells were increased,mitochondria distended, endoplasmic reticulum dilated and the number of melanosome declined in the group A.Conclusion Ge 132 can inhibit the melanocytes growth at a certain concentration and might be used for treating pigmented diseases.展开更多
Background: Melanocytes transplant for treatment of vitiligo is a common therapy using different surgical procedures. But there was no interest in repigmentation of grayness of hair in the treated vitiliginous area. O...Background: Melanocytes transplant for treatment of vitiligo is a common therapy using different surgical procedures. But there was no interest in repigmentation of grayness of hair in the treated vitiliginous area. Objective: To do melanocytes transplant from donor area into the recipient vitiliginous area with associated gray hair. Patient and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Eleven patients were enrolled in this study, six males and five females with vitiligo in association of gray hair. Their ages ranged from 8 - 35 years with a mean ±SD of 20.90 ± 7.006. Melanocytes transplant in patients with vitiligo using needling micrografting technique for twelve patches and direct melanocytes transplant from normal donor area into vitiliginous recipient area by dermabrasion technique for eleven patches. Dressing was applied and patients were seen every two weeks for the first month and monthly for one year. Results: Repigmentation of the vitiliginous area was started after two weeks and was obvious at one month that progressed over time. The repigmentation of hair appeared usually after few months and was obvious after four months and the repigmentation of gray hair was quicker in patients with micrografting technique than those with dermabrasion technique. The mean rate of repigmentation was 18.3% at six months and 37.5% at twelve months in micrografting technique while the mean rate of repigmentation was 9.15% at six months and 18.55 at twelve months in dermabrasion technique. Conclusions: Direct transplant of melanocytes from normal donor area into recipient vitiliginous area with associated white hair is an effective procedure to induce repigmentation of gray hair.展开更多
Background: Vitiligo is an autoimmune pigmentory disorder, that affects all age group that is treated by many medical treatments but some of them might need surgical therapy. Objective: To evaluate the dermabrasion te...Background: Vitiligo is an autoimmune pigmentory disorder, that affects all age group that is treated by many medical treatments but some of them might need surgical therapy. Objective: To evaluate the dermabrasion technique in the treatment of vitiligo by direct transfer of melanocytes from the dermabraded normal donor area to the vitiliginous recipient area. Patients and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Nine Patients with vitiligo were enrolled in this study with different clinical types of vitiligo including 5 segmental, 2 generalized and 2 localized. The donor and recipient areas were anesthetized at the same time with xylocain alone. Dermabrasion of recipient area was done first by manual abrader and left for few minutes until the oozing was stopped. Then the donor area was similarly dermabraded and the dermabraded tissue including the epidermis and superficial epidermis was immediately transferred into the recipient area and dressing was applied. Removal of the dressing was done after 10 - 14 days from the operative time. Follow up was done every 2 weeks in the first month then monthly for six months to record the result of implantation and repigmentation. Results: The re-pigmentation started one month after the operation as small macules and this increased gradually over time: the mean rate of re-pigmentation was 13% at 2 months, 27.8% at 4 months and 36.78% at 6 months. In addition, sun light exposure was applied to enhance re-pigmentation. The pigmentation was diffuse and not follicular in shape. Conclusion: Direct transfer of melanocytes from normal donor area into vitiliginous recipient area by dermabrasion technique was easy, rapid and non-costly and gave 36.78% mean rate of pigmentation at 6 months follow up and without complications.展开更多
Bidens segetum Martius ex Colla known as the “picão do mato”, is an herbaceous plant that occurs in the Cerrado biome of some Brazilian states. Among the species of Bidens, we highlight B. pilosa known as...Bidens segetum Martius ex Colla known as the “picão do mato”, is an herbaceous plant that occurs in the Cerrado biome of some Brazilian states. Among the species of Bidens, we highlight B. pilosa known as “picão preto”, of which several activities are reported as antioxidant and antibacterial. Ethanolic extract from Bidens segetum (EEBs) showed an-tioxidant potential when analyzed by free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and antifungal activity against Cladosporium cladosporiodes and C. sphareospermum fungi. PFFR3.3 subfraction from EEBs has 81.5% of 5-O caffeoylquinic acid (5-CQA) and potential antioxidant (DPPH). However, PFFR3.3 did not decrease superoxide anion in metastatic melanoma cells by dihydroeth-idium assay (DHE). PP4 subfraction is a mixture of polyacetylenes that has antifungal (Cladosporium) and antioxidant activity, since reduced superoxide anion amount in melanoma cells after 5 min of treatment. However, no dose-response and time-response curve were observed, not even with the authentic standard (5-CQA). Complementary chemical studies will be performed to confirm the polyacetylenes and 5-CQA structures present in the EEBs from B. segetum and new methodologies should be performed to confirm the antioxidant activity of these com-pounds and the effects on melanocytes and melanomas.展开更多
Secreted frizzled-related protein 5(SFRP5)plays a pivotal role in regulating the development of many tissues and organs,however,as an inhibitor of Wnt signaling,the role of SFRP5 in vitiligo remains unknown.Hence,we s...Secreted frizzled-related protein 5(SFRP5)plays a pivotal role in regulating the development of many tissues and organs,however,as an inhibitor of Wnt signaling,the role of SFRP5 in vitiligo remains unknown.Hence,we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo.In this study,we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo.Compared with that in normal epidermal melanocytes(PIG1),the expression of SFRP5 was increased in vitiligo melanocytes(PIG3V).To investigate the effect of SFRP5 on melanin synthesis,PIG1 cells were infected with recombinant SFRP5 adenovirus(AdSFRP5),and PIG3V cells were infected with recombinant siSFRP5 adenovirus(AdsiSFRP5).The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor(MITF)and its target proteins via suppression of the Wnt/b-catenin signaling pathway.Accordingly,SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells.Moreover,SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor(TCF/LEF)in PIG1 cells.Furthermore,this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the b-catenin agonist,SKL2001.The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model.Hence,our results indicate that SFRP5 can inhibit melanogenesis in melanocytes.Additionally,our findings showed that SFRP5 plays a vital role in the development of vitiligo,and thus may serve as a potential therapeutic target for vitiligo.展开更多
Objective To investigate the effect of Q switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota Methods Multiple biopsies were carried out on 4 patients with nevus of Ota before and after laser i...Objective To investigate the effect of Q switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota Methods Multiple biopsies were carried out on 4 patients with nevus of Ota before and after laser irradiation Altogether 11 samples were examined under light microscope and 14 under transmission electron microscope Results Immediately after laser irradiation, the dermal melanocytes were destroyed, the melanosomes were degenerated with central vesicle formation within most of them, and intradermal round vacuoles appeared The epidermis remained intact Three months to 1 year after irradiation, the degenerated melanosomes and cell debris were scavenged mainly by macrophages Dermal melanocytes gradually decreased No fibrosis was found Conclusion Q switched alexandrite laser can selectively destroy dermal melanocytes of nevus of Ota and treat the disease展开更多
Vitiligo,a common skin depigmentation disorder,is the result of complex interactions of genetic,immunological,environmental,and biochemical events.Treatments for vitiligo include drugs,phototherapy,surgical transplant...Vitiligo,a common skin depigmentation disorder,is the result of complex interactions of genetic,immunological,environmental,and biochemical events.Treatments for vitiligo include drugs,phototherapy,surgical transplantation,and so on.Among them,the efficacy of narrow band-ultraviolet B has been confirmed.By inducing keratinocytederived factors and signalings,narrow band-ultraviolet B can trigger and/or promote the mobilization of melanocytes which migrate to lesional epidermis ultimately,leads to the repigmentation of white patches.The mobilization of melanocytes includes stages of activation,migration,proliferation,and differentiation.Elucidating processes that enable the specific mobilization of melanocytes and the signaling pathways and factors involved,will help the development of new drugs and methods for the treatment of vitiligo.展开更多
Objective:To elucidate the epidermal melanocyte distribution according to sex,age,and body part with the goal of providing benchmark data for the diagnosis and therapeutic effect evaluation of pigmentary skin diseases...Objective:To elucidate the epidermal melanocyte distribution according to sex,age,and body part with the goal of providing benchmark data for the diagnosis and therapeutic effect evaluation of pigmentary skin diseases.Methods:Epidermal melanocytes and keratinocytes were assessed using direct immunofluorescence staining,and the melanocyte density and epidermal thickness were calculated.The obtained data were statistically analyzed using SPSS Version 20.0 software.An independent-samples t test was used to compare the data between two groups,while data among three or more groups were compared by one-way analysis of variance.Data correlations were evaluated using Pearson correlation analysis.Results:Melanocytes were uniformly distributed among the keratinocytes in the basal layer,and the average ratio of melanocytes to keratinocytes was 1:7.Among them,the ratio in males was 1:6.5 and that in females was 1:7.4,with no significant difference(P=0.127).The melanocyte density gradually declined as age increased;the ratio was 1:5.8 before 50 years of age without an obvious downtrend.The average melanocyte density was 1:7.9 within 51 to 65 years of age and 1:8.5 at>65 years of age,and the difference was statistically significant(P<0.01).Obvious differences were found in the melanocyte density among different body parts;in descending order,these densities were as follows:face(1:4.0)>neck(1:5.1)>hip(1:5.7)>upper limb(1:7.4)>lower limb(1:8.3)>lower back(1:9.2)>thorax and abdomen(1:9.9).The melanocyte density was not related to the epidermal thickness.Conclusion:The melanocyte density showed a declining trend with age and significantly changed after 50 years of age.The melanocyte density was associated with body part;specifically,the density in the face,neck,and hip was higher than that in the limbs and torso.However,the melanocyte density was not associated with sex or epidermal thickness.展开更多
BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation.Insufficient data published in the literature do not allow for diagnostic and treatment guideli...BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation.Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established.Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.CASE SUMMARY A 66-year-old woman presented with intermittent anal bleeding,pain,and tenesmus in the past month,with no associated weight loss.Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm,with exulcerated areas and an adherent clot but without obstruction.Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis.Tumour markers CA 19-9 and CEA were within the normal range.After 6 mo,due to the persistence of symptoms,a pelvic magnetic resonance imaging scan was performed.A lesion measuring 2.8 cm×2.7 cm×2.1 cm was identified at the anorectal junction,along with two adjacent lymphadenopathies.No distant metastases were detected.Immunohistochemistry was performed on the second set of biopsies,and a diagnosis of anorectal melanoma was established.Surgical treatment by abdominoperineal resection was performed.Evolution was marked by the appearance of lung metastases at 1 mo postoperatively,detected on a positron emission tomography-computer tomography scan,and perineal recurrence after 5 mo.After molecular testing,the patient was included in an immunotherapy trial.CONCLUSION This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma,the importance of performing histological analysis on a wellrepresented biopsy specimen,and the poor prognosis,even with radical surgery.展开更多
We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional borde...We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.展开更多
Adalimumab, a TNF-alpha antagonist, is the first fully humanized recombinant immunoglobulin G1 (IgG1) monoclonal antibody. It is presently widely used in the systemic treatment of rheumatoid arthritis, inflammatory bo...Adalimumab, a TNF-alpha antagonist, is the first fully humanized recombinant immunoglobulin G1 (IgG1) monoclonal antibody. It is presently widely used in the systemic treatment of rheumatoid arthritis, inflammatory bowel disease, moderate and severe psoriasis and hidradenitis suppurativa. However, its administration is associated with a two-fold risk of severe and possibly fatal infections and in some rare cases with congestive heart failure, lymphoma, lupus-like syndrome, cytopenias, hepatotoxicity and development of demyelinating neurological disorders. Furthermore, the occurrence of various types of melanocytic skin lesions has been reported during treatment with adalimumab. In the present paper we report the case of a female psoriatic patient who developed eruptive lentigines following treatment with this compound.展开更多
AIM: To describe the histopathologic and clinical features of eyelid tumor cases from Tianjin Eye Hospital during 2002 to 2015. METHODS: In this retrospective study, a total of 2228 cases of eyelid tumors with patholo...AIM: To describe the histopathologic and clinical features of eyelid tumor cases from Tianjin Eye Hospital during 2002 to 2015. METHODS: In this retrospective study, a total of 2228 cases of eyelid tumors with pathologic diagnoses were enrolled. The eyelid tumors were classified into three groups according to tumor origin: epidermal, adnexal and miscellaneous, including melanocytic, neural and vascular lesions. Inflammatory tumor-like lesions were excluded. The clinical characteristics of the eyelid tumors were analyzed, including age, gender and lesion location. RESULTS: Most eyelid tumors were epidermal in origin(1080, 48.5%), followed by miscellaneous(885, 39.7%) and adnexal tumors(263, 11.8%). Among all the tumors, 292(13.1%) were malignant lesions, 1910(85.7%) benign and 26(1.1%) premalignant lesions. Most malignant tumors originated from epidermal cells(60.0%), followed by adnexal cells(34.6%). The most common malignant tumors were basal cell carcinomas(56.5%) followed by sebaceous carcinoma(34.6%), squamous cell carcinomas(3.8%) and lymphoma/plasmocytoma(1.7%). The benign and premalignant eyelid lesions mostly originated from epidermal cells(46.4%) followed by miscellaneous cell sources(45.2%), including melanocytic nevus(33.8%), seborrheic keratosis(13.7%), squamous cell papilloma(13.0%) and epidermal cysts(11.5%). CONCLUSION: Eyelid tumors are mostly epithelial in origin. Benign tumors are significantly more common than malignant tumors with an obvious female predominance, and the most frequent malignant tumor are basal cell carcinoma, sebaceous carcinoma and squamous cell carcinomas. The tumor clinical features varied among the different subtypes.展开更多
基金funded by the Natural Science Foundation of Anhui Province,China(2008085QC158)the University Natural Science Research Project of Anhui Province(KJ2019A0165)。
文摘In mammals,microRNAs(miRNAs)play key roles in multiple biological processes by regulating the expression of target genes.Studies have found that the levels of miR-370-5p expression differ significantly in the skins of sheep with different hair colors;however,its function remains unclear.In this study,we investigated the roles of miR-370-5p in sheep melanocytes and found that the overexpression of miR-370-5p significantly inhibited cell proliferation(P<0.01),tyrosinase activity(P=0.001)and significantly reduced(P<0.001)melanin production.Functional prediction revealed that the 3′-untranslated region(UTR)of MAP3K8 has a putative miR-370-5p binding site,and the interaction between these two molecules was confirmed using luciferase reporter assays.In situ hybridization assays revealed that MAP3K8 is expressed in the cytoplasm of melanocytes.The results of quantitative RT-PCR and Western blotting analyses revealed that overexpression of miR-370-5p in melanocytes significantly inhibits(P<0.01)MAP3K8 expression via direct targeting of its 3′UTR.Inhibition of MAP3K8 expression by siRNA-MAP3K8 transfection induced a significant inhibition(P<0.01)of melanocyte proliferation and significant reduction(P<0.001)in melanin production,which is consistent with our observations for miR-370-5p.Target gene rescue experiments indicated that the expression of MAP3K8 in melanocytes co-transfected with miR-370-5p and MAP3K8-cDNA(containing sites for the targeted binding to miR-370-5p)was significantly rescued(P≤0.001),which subsequently promoted significant increases in cell proliferation(P<0.001)and melanin production(P<0.01).Collectively,these findings indicate that miR-370-5p plays a functional role in inhibiting sheep melanocyte proliferation and melanogenesis by downregulating the expression of MAP3K8.
文摘Although perifollicular repigmentation in the vitiligo lesions is owing to activation of follicular melanocyte stem cells and/or precursor cells followed by supplying matured melanocytes, the underlying mechanism of diffuse repigmentation on the whole vitiligo surface remains still unknown. In addition to the presence of remaining melanocytes, it is conceivable that dermal melanocyte precursor cells contribute to induce diffuse repigmentation after treatment. Therefore, we investigated here whether dermal and follicular melanocyte precursor cells were reduced or not in vitiligo lesions. We performed an immunostaining for Nestin and p75NGFR as dermal melanocyte precursor cells and MITF/Fzd4 as follicular melanocyte precursor cells and compared the positive cells number between lesions and non-lesions (n = 11). Although MITF<sup>+</sup>/Fzd4<sup>+</sup> cells in the hair follicle were significantly decreased in number in the lesions, Nestin<sup>+</sup> and p75NGFR<sup>+</sup> cells were not. This result indicates that dermal precursor cells could be retained in the vitiligo lesions but be disturbed to differentiate into matured melanocytes.
文摘Background: Vitiligo is a common autoimmune inflammatory skin disease, where there are different surgical techniques for treatment of stable patches of vitiligo .Objective: To find non-costly, minimally invasive, simple technique by direct melanocytes transplant by spade needle technique in treatment of vitiligo. Patients and Methods: This interventional, therapeutic, comparative study was done in Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq from April 2014-March 2015. Twenty patients with localized, generalized and segmental vitiligo were included. Full history and examination for each patient was done with 4 (20%) males and 16 (80%) females and their ages ranged from 9 - 40 (23.15 ± 11.44) years. Forty one patches in 20 patients treated by spade grafting technique and the donor and recipient sites were demarcated and anesthesia done by xylocaine 2% with adrenalin 1:100,000. Transplantation was started by using disposable needle gauge 18 (the sharp end of needle was cut by a scissor to make it a spade like) with medical syringe 5 ml supplied with normal saline. The micro-pieces were taken from donor site and transplanted directly, easily and rapidly into dermis of recipient site and followed by pushing normal saline and the procedure was repeated to cover all recipient sites with 5 mm distance between injection points. The surface area of the lesions was calculated and the reduction rate was estimated every month till the end of the 4th month period of the treatment. Results: Including 41 patches in 20 patients with the surface area of the patches ranged from 1.5 - 90 cm<sup>2</sup> (13.78 ± 17.57) cm<sup>2</sup>. The mean ±SD of surface area of lesions was decreased from 13.78 ± 17.57 cm<sup>2</sup> at baseline visit to 13.61 ± 17.48 cm<sup>2</sup> at the second visit (after 2 weeks ) which was statistically significant (p value ≤ 0.001). The mean surface area continued to be reduced till reaching 12.20 ± 15.68 cm<sup>2</sup> at the third visit and 12.01 ± 15.55 cm<sup>2</sup> at the fourth visit. All were statistically significant when compared to baseline visit. There was reduction in surface area 1.1% at two weeks, 9.93%, and 12.5% at the 2nd, 4th months respectively. Conclusions: Intradermal injection of melanocytes in patients with vitiligo by spade like needle was very quick and simple non-costly technique, and gave 12.5% reduction which could be repeated at different times until satisfactory re-pigmentation of vitiligenous skin is achieved.
文摘Objective To find direct effect of Chinese herbs Bu Gu Zhi (Psoralea corylifolia L) and Bai Zhi (Dahurian angelica root) Extracts on melanocyte adhesion and migration in vitro. Methods Ethanol extracts obtained from two kind of Chinese medicinable herbs were tested. Human melanocytes were obtained from neonatal foreskins and 48-well culture dish covered with fibronectin were used to perform melanocyte adhesion assay; Motility was assessed using the micropore filter method. Results: The extracts of Bu Gu Zhi(Psoralea corylifolia L), Bai Zhi(Dahurian angelica root) obviously showed an effect in increasing of human melanocyte adhesion and migration on fibronectin. Conclusion It is suggested that Buguzhi(Fructus Psoraleae) and Baizhi(Radix Angelicae Dahuricae) might induce melanocyte adhesion and/or migration in the treatment of vitiligo.
文摘Keishibukuryogankayokuinin (KBY) is a traditional Japanese herbal medicine widely used to treat skin pigmentation. The scientific basis for its use is, however, unclear, and studies evaluating its mechanism and effectiveness are sparse. In this study, we compared the tyrosinase inhibitory effects of KBY and Keishibukuryogan (KB, which has the same composition of KBY, except Coix Seed [CS]) and CS under exposure to UV radiation as well as under non-exposure conditions. Neonatal human epidermal melanocytes obtained from a darkly pigmented donor were used. These cells were cultured in a final concentration of 500 μg/ml or 1000 μg/ml, to which KBY, KB, and CS were added. After incubation for 72 h, cells were stained with Fontana-Masson stain and counted. Tyrosinase activity was measured by its dopa oxidase activity, and tyrosinase expression was estimated using real-time PCR. For UV radiation, cells were exposed to UVB radiation for 90 s per day for 3 days. Under non-exposure conditions, tyrosinase activity significantly increased with both KBY and KB but significantly decreased with CS, regardless of the concentration. In addition, tyrosinase expression significantly decreased but only with KBY at both concentrations. Under UV radiation exposure, tyrosinase activity significantly increased with KBY and KB at both concentrations while tyrosinase expression significantly decreased with KBY and KB;a significant increase was, however, observed with CS at both concentrations. These results suggest that taking KBY after sunburn is effective against skin pigmentation, and the combination of KB and CS is useful for skin depigmentation.
文摘Objective To elucidate the effect of Ge 132 on the growth of melanocytes.Methods Melanocyes from epidermis were cultured and purified;the second generation of the cell was used for study;the cells were divided into two groups randomly,to group A, Ge 132 was added to the media at 0.04mg/L;to group B,common culturing method was used without Ge 132.After 5d, the cells were seperated by digestion for study by transmission electronic microscope.Results Compared to group B, the vaculoes of the cells were increased,mitochondria distended, endoplasmic reticulum dilated and the number of melanosome declined in the group A.Conclusion Ge 132 can inhibit the melanocytes growth at a certain concentration and might be used for treating pigmented diseases.
文摘Background: Melanocytes transplant for treatment of vitiligo is a common therapy using different surgical procedures. But there was no interest in repigmentation of grayness of hair in the treated vitiliginous area. Objective: To do melanocytes transplant from donor area into the recipient vitiliginous area with associated gray hair. Patient and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Eleven patients were enrolled in this study, six males and five females with vitiligo in association of gray hair. Their ages ranged from 8 - 35 years with a mean ±SD of 20.90 ± 7.006. Melanocytes transplant in patients with vitiligo using needling micrografting technique for twelve patches and direct melanocytes transplant from normal donor area into vitiliginous recipient area by dermabrasion technique for eleven patches. Dressing was applied and patients were seen every two weeks for the first month and monthly for one year. Results: Repigmentation of the vitiliginous area was started after two weeks and was obvious at one month that progressed over time. The repigmentation of hair appeared usually after few months and was obvious after four months and the repigmentation of gray hair was quicker in patients with micrografting technique than those with dermabrasion technique. The mean rate of repigmentation was 18.3% at six months and 37.5% at twelve months in micrografting technique while the mean rate of repigmentation was 9.15% at six months and 18.55 at twelve months in dermabrasion technique. Conclusions: Direct transplant of melanocytes from normal donor area into recipient vitiliginous area with associated white hair is an effective procedure to induce repigmentation of gray hair.
文摘Background: Vitiligo is an autoimmune pigmentory disorder, that affects all age group that is treated by many medical treatments but some of them might need surgical therapy. Objective: To evaluate the dermabrasion technique in the treatment of vitiligo by direct transfer of melanocytes from the dermabraded normal donor area to the vitiliginous recipient area. Patients and Methods: This is a case interventional study was done in Department of Dermatology/Baghdad Teaching Hospital from February 2011-March 2012. Nine Patients with vitiligo were enrolled in this study with different clinical types of vitiligo including 5 segmental, 2 generalized and 2 localized. The donor and recipient areas were anesthetized at the same time with xylocain alone. Dermabrasion of recipient area was done first by manual abrader and left for few minutes until the oozing was stopped. Then the donor area was similarly dermabraded and the dermabraded tissue including the epidermis and superficial epidermis was immediately transferred into the recipient area and dressing was applied. Removal of the dressing was done after 10 - 14 days from the operative time. Follow up was done every 2 weeks in the first month then monthly for six months to record the result of implantation and repigmentation. Results: The re-pigmentation started one month after the operation as small macules and this increased gradually over time: the mean rate of re-pigmentation was 13% at 2 months, 27.8% at 4 months and 36.78% at 6 months. In addition, sun light exposure was applied to enhance re-pigmentation. The pigmentation was diffuse and not follicular in shape. Conclusion: Direct transfer of melanocytes from normal donor area into vitiliginous recipient area by dermabrasion technique was easy, rapid and non-costly and gave 36.78% mean rate of pigmentation at 6 months follow up and without complications.
基金CNPq (Master Scholarship Simone Dias Franco) FAPESP (Grants No. 2014/14299-4 (07/2015-06/2017) and No. 2014/21593-2)
文摘Bidens segetum Martius ex Colla known as the “picão do mato”, is an herbaceous plant that occurs in the Cerrado biome of some Brazilian states. Among the species of Bidens, we highlight B. pilosa known as “picão preto”, of which several activities are reported as antioxidant and antibacterial. Ethanolic extract from Bidens segetum (EEBs) showed an-tioxidant potential when analyzed by free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and antifungal activity against Cladosporium cladosporiodes and C. sphareospermum fungi. PFFR3.3 subfraction from EEBs has 81.5% of 5-O caffeoylquinic acid (5-CQA) and potential antioxidant (DPPH). However, PFFR3.3 did not decrease superoxide anion in metastatic melanoma cells by dihydroeth-idium assay (DHE). PP4 subfraction is a mixture of polyacetylenes that has antifungal (Cladosporium) and antioxidant activity, since reduced superoxide anion amount in melanoma cells after 5 min of treatment. However, no dose-response and time-response curve were observed, not even with the authentic standard (5-CQA). Complementary chemical studies will be performed to confirm the polyacetylenes and 5-CQA structures present in the EEBs from B. segetum and new methodologies should be performed to confirm the antioxidant activity of these com-pounds and the effects on melanocytes and melanomas.
基金This work was supported by the National Natural Science Foundation of China[grant number 81773307]a research grant from Chongqing Science and Technology Commission[grant number cstc2018jcyjAX0195].
文摘Secreted frizzled-related protein 5(SFRP5)plays a pivotal role in regulating the development of many tissues and organs,however,as an inhibitor of Wnt signaling,the role of SFRP5 in vitiligo remains unknown.Hence,we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo.In this study,we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo.Compared with that in normal epidermal melanocytes(PIG1),the expression of SFRP5 was increased in vitiligo melanocytes(PIG3V).To investigate the effect of SFRP5 on melanin synthesis,PIG1 cells were infected with recombinant SFRP5 adenovirus(AdSFRP5),and PIG3V cells were infected with recombinant siSFRP5 adenovirus(AdsiSFRP5).The results showed that SFRP5 overexpression inhibited melanin synthesis in PIG1 cells through downregulation of microphthalmia-associated transcription factor(MITF)and its target proteins via suppression of the Wnt/b-catenin signaling pathway.Accordingly,SFRP5 silencing increased melanin synthesis and activated the Wnt signaling pathway in PIG3V cells.Moreover,SFRP5 overexpression also downregulated the transcriptional activity of T cell factor/lymphoid enhancer factor(TCF/LEF)in PIG1 cells.Furthermore,this inhibitory effect of SFRP5 on melanin synthesis was reversed by treatment with the b-catenin agonist,SKL2001.The inhibitory action of SFRP5 in pigmentation was further confirmed in vivo using a nude mouse model.Hence,our results indicate that SFRP5 can inhibit melanogenesis in melanocytes.Additionally,our findings showed that SFRP5 plays a vital role in the development of vitiligo,and thus may serve as a potential therapeutic target for vitiligo.
文摘Objective To investigate the effect of Q switched alexandrite laser irradiation on dermal melanocytes of nevus of Ota Methods Multiple biopsies were carried out on 4 patients with nevus of Ota before and after laser irradiation Altogether 11 samples were examined under light microscope and 14 under transmission electron microscope Results Immediately after laser irradiation, the dermal melanocytes were destroyed, the melanosomes were degenerated with central vesicle formation within most of them, and intradermal round vacuoles appeared The epidermis remained intact Three months to 1 year after irradiation, the degenerated melanosomes and cell debris were scavenged mainly by macrophages Dermal melanocytes gradually decreased No fibrosis was found Conclusion Q switched alexandrite laser can selectively destroy dermal melanocytes of nevus of Ota and treat the disease
基金The authors are very grateful to Professor V.J.Hearing for help with the English-language editing.The work was supported by the National Nature Science Foundation of China(No.81673078).
文摘Vitiligo,a common skin depigmentation disorder,is the result of complex interactions of genetic,immunological,environmental,and biochemical events.Treatments for vitiligo include drugs,phototherapy,surgical transplantation,and so on.Among them,the efficacy of narrow band-ultraviolet B has been confirmed.By inducing keratinocytederived factors and signalings,narrow band-ultraviolet B can trigger and/or promote the mobilization of melanocytes which migrate to lesional epidermis ultimately,leads to the repigmentation of white patches.The mobilization of melanocytes includes stages of activation,migration,proliferation,and differentiation.Elucidating processes that enable the specific mobilization of melanocytes and the signaling pathways and factors involved,will help the development of new drugs and methods for the treatment of vitiligo.
文摘Objective:To elucidate the epidermal melanocyte distribution according to sex,age,and body part with the goal of providing benchmark data for the diagnosis and therapeutic effect evaluation of pigmentary skin diseases.Methods:Epidermal melanocytes and keratinocytes were assessed using direct immunofluorescence staining,and the melanocyte density and epidermal thickness were calculated.The obtained data were statistically analyzed using SPSS Version 20.0 software.An independent-samples t test was used to compare the data between two groups,while data among three or more groups were compared by one-way analysis of variance.Data correlations were evaluated using Pearson correlation analysis.Results:Melanocytes were uniformly distributed among the keratinocytes in the basal layer,and the average ratio of melanocytes to keratinocytes was 1:7.Among them,the ratio in males was 1:6.5 and that in females was 1:7.4,with no significant difference(P=0.127).The melanocyte density gradually declined as age increased;the ratio was 1:5.8 before 50 years of age without an obvious downtrend.The average melanocyte density was 1:7.9 within 51 to 65 years of age and 1:8.5 at>65 years of age,and the difference was statistically significant(P<0.01).Obvious differences were found in the melanocyte density among different body parts;in descending order,these densities were as follows:face(1:4.0)>neck(1:5.1)>hip(1:5.7)>upper limb(1:7.4)>lower limb(1:8.3)>lower back(1:9.2)>thorax and abdomen(1:9.9).The melanocyte density was not related to the epidermal thickness.Conclusion:The melanocyte density showed a declining trend with age and significantly changed after 50 years of age.The melanocyte density was associated with body part;specifically,the density in the face,neck,and hip was higher than that in the limbs and torso.However,the melanocyte density was not associated with sex or epidermal thickness.
文摘BACKGROUND Anorectal melanoma is a tumour that is difficult to identify due to its rarity and variability of presentation.Insufficient data published in the literature do not allow for diagnostic and treatment guidelines to be established.Anorectal melanoma has the worst prognosis among mucosal melanomas and is frequently misdiagnosed by standard identification methods.CASE SUMMARY A 66-year-old woman presented with intermittent anal bleeding,pain,and tenesmus in the past month,with no associated weight loss.Colonoscopy revealed a cauliflower-like tumour with a diameter of 1.5 cm,with exulcerated areas and an adherent clot but without obstruction.Biopsy results identified an inflammatory rectal polyp with nonspecific chronic rectitis.Tumour markers CA 19-9 and CEA were within the normal range.After 6 mo,due to the persistence of symptoms,a pelvic magnetic resonance imaging scan was performed.A lesion measuring 2.8 cm×2.7 cm×2.1 cm was identified at the anorectal junction,along with two adjacent lymphadenopathies.No distant metastases were detected.Immunohistochemistry was performed on the second set of biopsies,and a diagnosis of anorectal melanoma was established.Surgical treatment by abdominoperineal resection was performed.Evolution was marked by the appearance of lung metastases at 1 mo postoperatively,detected on a positron emission tomography-computer tomography scan,and perineal recurrence after 5 mo.After molecular testing,the patient was included in an immunotherapy trial.CONCLUSION This case highlights the difficulty of establishing a definitive early diagnosis of anorectal melanoma,the importance of performing histological analysis on a wellrepresented biopsy specimen,and the poor prognosis,even with radical surgery.
文摘We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.
文摘Adalimumab, a TNF-alpha antagonist, is the first fully humanized recombinant immunoglobulin G1 (IgG1) monoclonal antibody. It is presently widely used in the systemic treatment of rheumatoid arthritis, inflammatory bowel disease, moderate and severe psoriasis and hidradenitis suppurativa. However, its administration is associated with a two-fold risk of severe and possibly fatal infections and in some rare cases with congestive heart failure, lymphoma, lupus-like syndrome, cytopenias, hepatotoxicity and development of demyelinating neurological disorders. Furthermore, the occurrence of various types of melanocytic skin lesions has been reported during treatment with adalimumab. In the present paper we report the case of a female psoriatic patient who developed eruptive lentigines following treatment with this compound.
文摘AIM: To describe the histopathologic and clinical features of eyelid tumor cases from Tianjin Eye Hospital during 2002 to 2015. METHODS: In this retrospective study, a total of 2228 cases of eyelid tumors with pathologic diagnoses were enrolled. The eyelid tumors were classified into three groups according to tumor origin: epidermal, adnexal and miscellaneous, including melanocytic, neural and vascular lesions. Inflammatory tumor-like lesions were excluded. The clinical characteristics of the eyelid tumors were analyzed, including age, gender and lesion location. RESULTS: Most eyelid tumors were epidermal in origin(1080, 48.5%), followed by miscellaneous(885, 39.7%) and adnexal tumors(263, 11.8%). Among all the tumors, 292(13.1%) were malignant lesions, 1910(85.7%) benign and 26(1.1%) premalignant lesions. Most malignant tumors originated from epidermal cells(60.0%), followed by adnexal cells(34.6%). The most common malignant tumors were basal cell carcinomas(56.5%) followed by sebaceous carcinoma(34.6%), squamous cell carcinomas(3.8%) and lymphoma/plasmocytoma(1.7%). The benign and premalignant eyelid lesions mostly originated from epidermal cells(46.4%) followed by miscellaneous cell sources(45.2%), including melanocytic nevus(33.8%), seborrheic keratosis(13.7%), squamous cell papilloma(13.0%) and epidermal cysts(11.5%). CONCLUSION: Eyelid tumors are mostly epithelial in origin. Benign tumors are significantly more common than malignant tumors with an obvious female predominance, and the most frequent malignant tumor are basal cell carcinoma, sebaceous carcinoma and squamous cell carcinomas. The tumor clinical features varied among the different subtypes.
