Preliminary study on the mechanism of POFUT1 in colorectal cancer.

To analyse the effect of POFUT1 (Protein O-Fucosyltransferase 1) on the proliferation, migration and apoptosis of colorectal cancer (CRC) cells and to explore its potential mechanism. The effects of POFUT1 silencing in vitro on the proliferation, migration, and apoptosis of CRC cells were investigated using the SW480 and RKO cell lines. The effect of POFUT1 expression on cell phenotype was detected by cell proliferation assay (CCK8), colony formation assay, flow cytometry, wound healing assay, transwell assay, cell apoptosis assay, etc. In vitro, silencing of POFUT1 resulted in decreased proliferation, cell cycle arrest, reduced migration and increased apoptosis of CRC cells. In CRC cells, POFUT1 plays a tumour-promoting role by promoting cell proliferation and migration and inhibiting apoptosis.

Inhibition of Fam114A1 protects melanocytes from apoptosis through higher RACK1 expression.

Fam114A1 is a gene closely related to the development of nerve cells, melanocytes, and nerve cells that originate from the neural crest of the embryonic ectoderm. Recent studies showed that Fam114A1 has a role in the occurrence of ankylosing myelitis spondylitis and autoimmune enteritis; still, its cellular function remains poorly understood. In this study, we investigated the effect of Fam114A1 on the biological activity of melanocytes. We found that the expression of Fam114A1 in vitiligo melanocytes (MCV-L, MCV-N, PI3V) was higher than that in normal melanocytes, and the biological function of melanocytes was significantly affected when the Fam114A1 gene was silenced. Inhibition of Fam114A1 increased proliferation, migration, and melanin synthesis proteins, decreased apoptosis, while its overexpression reversed this process. Mechanistically, we discovered that RACK1 is a target protein of Fam114A1 and that RACK1 can be negatively regulated by Fam114A1. Further study showed that Fam114A1 inhibition could not protect melanocytes from apoptosis once the expression of RACK1 protein was silenced. In summary, Fam114A1 is an effective regulatory protein for regulating the function of melanocytes. Inhibition Fam114A1 protects melanocytes from apoptosis through increasing RACK1.

Successful Treatment of Vitiligo on the Scalp of a 9-Year-Old Girl Using Autologous Cultured Pure Melanocyte Transplantation.

Leukotrichia frequently accompanies vitiligo on hairy areas such as the scalp. Treatment with conventional medical therapy is usually unsuccessful because of deficiencies in the melanocyte reservoir. We describe transplantation of autologous cultured pure melanocytes for scalp vitiligo with leukotrichia in a 9-year-old girl, resulting in almost complete and stable repigmentation of skin and hair.

Follow-up study of vitiligo patients treated with autologous epidermal sheet transplants.

BACKGROUND: Autologous epidermal transplantation is available for the treatment of stable vitiligo. However, the results of this technique are affected by many factors. OBJECTIVES: It is important to investigate the long-term results and factors that might influence the outcome of the autologous epidermal grafting technique to form a basis for guidance for patients with vitiligo. METHODS: We performed a follow-up study involving 173 patients (95 male, 78 female) with vitiligo vulgaris and 109 patients (59 male, 50 female) with segmental vitiligo who underwent autologous epidermal grafting. We investigated the long-term percentage of repigmentation and colour matching up to 13 years after treatment (mean 1.87 years). RESULTS: The mean percentage of repigmentation in the total of 1938 sheets was 80.65%. In patients with vitiligo vulgaris, 110 (63.6%) showed excellent repigmentation, 18 (10.4%) showed good, 4 (5.8%) showed fair and 12 (20.2%) showed poor repigmentation. In patients with segmental vitiligo, 83 (76%) showed excellent repigmentation, 10 (9%) showed good, 4 (4%) showed fair and 12 (11%) showed poor repigmentation. In segmental vitiligo, the degree of repigmentation was significantly higher than that in vitiligo vulgaris lesions. Better outcomes were obtained in female patients and less than 20 years old patients, whereas results in male patients and more than 20 years old were inferior in both vitiligo vulgaris and segmental vitiligo patients. The face and neck had a higher completely matching ratio in the treated area with the surrounding skin compared to the non-exposed sites. However, the face and neck had a lower repigmentation in vitiligo vulgaris. There was a higher ratio of Koebner phenomenon on the donor site and new lesions on the other sites in 45 no repigmentation patients. CONCLUSIONS: Autologous epidermal transplantation achieves a high percentage of repigmentation which is affected by sex, age, types, position, duration and the stability time before transplantation in vitiligo patients. A more perfect colour matching was obtained in exposure sites. Disease activity after transplantation was very important for repigmentation or not.

[Transcriptional regulation of breast cancer resistance protein].

Breast cancer resistance protein (BCRP), also known as ABCG2, is a member of the ATP-binding cassette (ABC) transporter superfamily, and is known to play important roles in cancer multidrug resistance. The BCRP promoter lacks a TATA-box and contains a CAAT-box, lots of AP1, AP2 sites and several putative Sp1 sites which are downstream of a putative CpG island. Several transcription factors, such as progesterone receptor (PR), estrogen receptor (ER), nuclear factor-κB (NF-κB), hypoxia-inducible factors (HIFs), nuclear factor erythroid 2-related factor 2 (Nrf2), aryl hydrocarbon receptor (AhR), peroxisome proliferator-activated receptors (PPARs) and Krüppel-like factor 5 (KLF5), have been recently shown to bind to their response elements in the promoter/enhancer to activate the transcription of BCRP. BCRP transcription can be influenced by proinflammatory cytokines, growth factors, and homeobox protein MSX2. Signaling pathways, such as Sonic hedgehog (Shh), Notch and RAR/RXR pathways, may also involve in the transcriptional regulation of BCRP. In addition, promoter methylation and histone acetylation are essential for the BCRP transcription, especially for the drug-induced BCRP expression. This paper reviews the recent research progresses in this field with an emphasis on the roles of transcription factors and epigenetics in the transcriptional regulation of BCRP.

Small-sized lesions of childhood vitiligo treated by autologous epidermal grafting.

BACKGROUND: Currently many children and adolescents with vitiligo fail to respond to traditional medical treatment. However, their parents want the lesion to be removed as soon as possible. Although surgical therapies are viable alternatives in refractory and stabilized vitiligo, there are rare reports on surgical therapies for childhood vitiligo. OBJECTIVE: To assess the effectiveness and feasibility of using suction blister epidermal grafting for small-sized childhood vitiligo. METHODS: Twenty children with small-sized lesions of stable vitiligo were treated using epidermal grafts and followed-up for 6-12 months. RESULTS: After 6-12 months of follow-up, treatment outcomes were excellent in 17 patients (85%), good in two patients (10%), and poor in one patient (5%), out of a total of 20 patients. The mean repigmentation rate was 88.55%. The location of the lesions was probably a factor in determining the outcomes of transplantation. No scar formation or other complications were observed in any patients. CONCLUSION: Suction blister autologous epidermal grafting is a rapid, safe, and effective treatment for stable childhood vitiligo, especially in refractory and stable children with small-sized lesions.

Clinical, pathologic, and ultrastructural studies of progressive macular hypomelanosis.

BACKGROUND: Progressive macular hypomelanosis (PMH), a condition of uncertain etiology, is characterized by asymptomatic hypopigmented macules, predominantly located on the trunk. To date, the study of this disease has been sporadic and there are still no clinical diagnostic criteria. The aim of this study was to investigate the histopathologic and ultrastructural characteristics of PMH, and propose the clinical diagnostic criteria of PMH. METHODS: The Wood's lamp and Confocal Laser Scanning Microscopy were used to observe the lesions' features. Skin biopsies were used for hematoxylin and eosin staining, melanin staining, antibodies staining of S-100 protein, tyrosinase-related protein-1(TRP-1) and tyrosinase (T311), and also for ultra-structural study. Melanocytes were isolated and cultured from the lesions. RESULTS: Under Wood's lamp examination, the lesions of PMH showed punctiform red fluorescence. Confocal Laser Scanning Microscopy observation of the lesion showed that its "pigmented ring" around the dermal papillae was intact, but its melanin content was decreased compared with the surrounding normal skin. Ferrous sulfate staining showed that melanin content in the lesion of PMH was significantly decreased compared with the normal skin (P < 0.05). S-100 staining showed that the number of positive cells in the basal layer had no statistical significance (P > 0.05) between the lesion areas (8.25 ± 0.96) and the surrounding normal skin (8.75 ± 1.71). TRP-1 staining showed no significant difference between lesion areas (4.25 ± 0.96) and the surrounding normal skin (4.50 ± 1.29) (P > 0.05), and T311 staining also showed no difference between lesion areas (4.01 ± 0.87) and the surrounding normal skin (4.30 ± 1.05) (P > 0.05). Ultra-structural studies revealed a large reduction in the number of mature melanosome from PMH lesions. There were many membrane-bound groups in PMH lesions with normal appearance the margin, which contained a number of smaller type II-IV melanosomes, which were distributed in clusters. No degradation of melanosomes was present in the lysosomal compartments of PMH lesions. When melanocytes from the PMH lesions were cultured in vitro, the morphology of those melanocytes showed no difference compared with normal melanocytes. CONCLUSION: As a result of the above findings, we discussed and summarized the PMH's clinical diagnostic criteria.

Transcriptional suppression of breast cancer resistance protein (BCRP) by wild-type p53 through the NF-kappaB pathway in MCF-7 cells.

Breast cancer resistance protein (BCRP) has been shown to confer multidrug resistance, but the mechanisms of its regulation are poorly understood. Here, we investigate the effects of wild-type and mutant p53, and nuclear factor kappa-B (NF-kappaB) (p50) on BCRP promoter activity in MCF-7 cells. Our results demonstrated that wild-type p53 markedly suppressed BCRP activity and enhanced the chemosensitivity of cells to mitoxantrone, whereas mutant p53 had little inhibitory effect. After inhibition of NF-kappaB, similar results were obtained. Following knockdown of endogenous p53, BCRP and p50 expressions were increased, and the chemosensitivity of the cells to mitoxantrone was decreased. We conclude that wild-type p53 acts as a negative regulator of BCRP gene transcription.

Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice.

BACKGROUND: Aging and aging-related disorders impair the survival and differentiation potential of bone marrow mesenchymal stem cells (MSCs) and limit their therapeutic efficacy. Induced pluripotent stem cells (iPSCs) may provide an alternative source of functional MSCs for tissue repair. This study aimed to generate and characterize human iPSC-derived MSCs and to investigate their biological function for the treatment of limb ischemia. METHODS AND RESULTS: Human iPSCs were induced to MSC differentiation with a clinically compliant protocol. Three monoclonal, karyotypically stable, and functional MSC-like cultures were successfully isolated using a combination of CD24(-) and CD105(+) sorting. They did not express pluripotent-associated markers but displayed MSC surface antigens and differentiated into adipocytes, osteocytes, and chondrocytes. Transplanting iPSC-MSCs into mice significantly attenuated severe hind-limb ischemia and promoted vascular and muscle regeneration. The benefits of iPSC-MSCs on limb ischemia were superior to those of adult bone marrow MSCs. The greater potential of iPSC-MSCs may be attributable to their superior survival and engraftment after transplantation to induce vascular and muscle regeneration via direct de novo differentiation and paracrine mechanisms. CONCLUSIONS: Functional MSCs can be clonally generated, beginning at a single-cell level, from human iPSCs. Patient-specific iPSC-MSCs can be prepared as an "off-the-shelf" format for the treatment of tissue ischemia.