Evaluating the diagnostic accuracy of heat shock proteins and their combination with Alpha-Fetoprotein in the detection of hepatocellular carcinoma: a meta-analysis.

BACKGROUND: A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. METHODS: Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. RESULTS: A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69-0.85) compared to 0.73 (95% CI: 0.65-0.80); specificity of 0.89 (95% CI: 0.81-0.95) compared to 0.86 (95% CI: 0.77-0.91); PLR of 7.4 (95% CI: 3.7-14.9) compared to 5.1 (95% CI: 3.3-8.1); NLR of 0.24 (95% CI: 0.16-0.37) compared to 0.31 (95% CI: 0.24-0.41); DOR of 30.19 (95% CI: 10.68-85.37) compared to 16.34 (95% CI: 9.69-27.56); and AUC of 0.90 (95% CI: 0.87-0.92) compared to 0.85 (95% CI: 0.82-0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82-0.95), 0.94 (95% CI: 0.82-0.98), 14.5 (95% CI: 4.6-45.4), 0.11 (95% CI: 0.06-0.20), 133.34 (95% CI: 29.65-599.61), and 0.96 (95% CI: 0.94-0.98) for the combination of HSPs and AFP. CONCLUSION: Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.

Comparative outcomes of autologous cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in piebaldism patients: A retrospective study.

PURPOSE: To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of piebaldism. PATIENTS AND METHODS: A retrospective study was conducted on 30 anatomically based lesions from nine piebaldism patients who underwent either CMT (n = 7) or NCES (n = 23) between 2018 and 2020. The extent of repigmentation and colour matching was evaluated in all recipient sites using a digital imaging analysis system. In addition, adverse effects have also been assessed by follow-up results. RESULTS: More than 75% repigmentation was achieved in 100% (7/7) and 60.9% (14/23) of the 30 lesions with the CMT and NCES, respectively. There were significant differences between the two methods in terms of repigmentation. The majority of patients had colour mismatches, and there was no discernible difference between the two surgical techniques. Adverse reactions rarely occurred. CONCLUSION: The present study suggested that autologous CMT may provide better repigmentation in piebaldism patients than NCES with no significant side effects.

Chinese newborn screening for the incidence of G6PD deficiency and variant of G6PD gene from 2013 to 2017.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common X-linked enzymopathies caused by G6PD gene variant. We aimed to provide the characteristics of G6PD deficiency and G6PD gene variant distribution in a large Chinese newborn screening population. We investigated the prevalence of G6PD in China from 2013 to 2017. Then, we examined G6PD activity and G6PD gene in representative Chinese birth cohort to explore the distribution of G6PD gene variant in 2016. We then performed multicolor melting curve analysis to classify G6PD gene variants in 10,357 neonates with activity-confirmed G6PD deficiency, and DNA Sanger sequencing for G6PD coding exons if hot site variants were not found. The screened population, organizations, and provinces of G6PD deficiency were increased from 2013 to 2017 in China. The top five frequency of G6PD gene variants were c.1376G>T, c.1388G>A, c.95A>G, c.1024C>T, and c.871G>A and varied in different provinces, with regional and ethnic features, and four pathogenic variant sites (c.152C>T, c.290A>T, c.697G>C, and c.1285A>G) were first reported. G6PD deficiency mainly occurs in South China, and the frequency of G6PD gene variant varies in different regions and ethnicities.

[IL-6 promotes gastric cancer cell proliferation and EMT through regulating miR-152/PIK3R3 pathway].

OBJECTIVE: To explore the role of interleukin (IL)-6 in gastric cancer cells and the mechanisms.
 Methods: Gastric cancer cells MGC-803 were treated with 50 ng/mL of recombinant IL-6 protein, and then cell viability and cell migration were detected by MTT assay and wound-healing assay, respectively. The mRNA and protein expressions of E-cadherin, N-cadherin, vimentin, Snail1 and miR-152 were analyzed by RT-qPCR and Western blot, respectively. Moreover, MGC-803 cells were simultaneously or separately treated with IL-6 and transfected with miR-152 mimics, and then the mRNA expression of PIK3R3 and the protein levels of PIK3R3, Akt and p-Akt were determined.
 Results: IL-6 stimulation significantly promoted cell proliferation and migration, reduced the expression of E-cadherin and miR-152, and increased the expression of N-cadherin, vimentin, Snail1, PIK3R3 and p-Akt (All P<0.05). The protein levels of PIK3R3 and p-Akt were significantly decreased after transfecting miR-152 mimics into MGC-803 cells (P<0.01). miR-152 overexpression down-regulated IL-6-induced the protein expression of PIK3R3 and p-Akt (P<0.01). The levels of Akt in each group were not changed.
 Conclusion: IL-6 up-regulates PIK3R3 expression and activates PI3K/Akt signaling pathway through down-regulating miR-152 expression, which consequently promotes gastric cancer cell proliferation, migration, and epithelial-mesenchymal transition.

Epigallocatechin-3-gallate (EGCG) Suppresses the Trafficking of Lymphocytes to Epidermal Melanocytes via Inhibition of JAK2: Its Implication for Vitiligo Treatment.

Vitiligo is an inflammatory skin disorder in which activated T cells play an important role in its onset and progression. Epigallocatechin-3-gallate (EGCG), the major chemical constituent of green tea, exhibits remarkable anti-oxidative and anti-inflammatory properties. EGCG administration has been confirmed to decrease the risk of vitiligo; however, the underlying mechanism is undetermined. In this study, we proved that EGCG directly inhibited the kinase activity of Janus kinase 2 (JAK2). In primary cultured human melanocytes, EGCG pre-treatment attenuated interferon (IFN)-γ-induced phosphorylation of JAK2 and its downstream signal transducer and activator of transcription (STAT)1 and STAT3 in a dose-dependent manner. We further examined the chemoattractant expression in melanocytes and demonstrated that EGCG significantly inhibited IFN-γ-induced expression of intracellular adhesion molecule (ICAM)-1, CXCL10, and monocyte chemotactic protein (MCP)-1 in human melanocytes. In addition, EGCG reduced the protein levels of the corresponding receptors including CD11a, CXCR3, and CCR2 in human T lymphocytes. As a consequence, adhesion of human T cells to melanocytes induced by IFN-γ was effectively suppressed by EGCG. Taken together, our results provided new evidence for the effectiveness of EGCG in vitiligo treatment and supported JAK2 as a molecular target for vitiligo medicine development.

A randomized controlled study of the effects of different modalities of narrow-band ultraviolet B therapy on the outcome of cultured autologous melanocytes transplantation in treating vitiligo.

BACKGROUND: Vitiligo is an acquired skin disorder with great social impact. It can be successfully treated using cultured autologous melanocytes transplantation. OBJECTIVE: To evaluate the effect of different modalities of narrow-band ultraviolet B (NB-UVB) therapy on the outcome of cultured autologous melanocyte transplantation in treating vitiligo. METHODS: Patients undergoing cultured autologous melanocyte transplantation were randomly assigned to four different study groups. Group 1 underwent 20 sessions of NB-UVB treatment before transplantation; Group 2 underwent 30 sessions of NB-UVB treatment after transplantation; Group 3 underwent 20 sessions of NB-UVB treatment before transplantation and 30 sessions after transplantation; Group 4 underwent only transplantation. RESULTS: Four hundred thirty-seven patients were enrolled. Group 3 responded best, more than 90% repigmentation was achieved in 81.3% of patients, and 94.8% patients experienced 50% or greater repigmentation. Statistical analysis showed that there was a highly significant difference between the four groups (χ(2) = 35.56, p < .001). Homogeneous skin color was obtained on the repigmentation areas, and no scarring or other serious side effects were observed. CONCLUSIONS: Cultured autologous melanocyte transplantation is an effective treatment for stable vitiligo. Combination of NB-UVB therapy with melanocyte transplantation can accelerate repigmentation of transplanted vitiliginous areas, especially if NB-UVB is given before and after transplantation.

Target area treatment ratio of varied lesions in the cultured pure melanocyte transplantation repigmentation of vitiligo: A retrospective study.

Autologous cultured pure melanocyte transplantation (CMT) can be utilized to treat stable vitiligo cases, but clinical data are insufficient to improve its efficacy. To evaluate the influence of various factors on the therapeutic effect of CMT, this single-center retrospective study enrolled stable vitiligo patients who underwent CMT between 2009 and 2020. Univariate and multivariable analysis were used to determine the factors affecting the outcome of repigmentation. The study included 491 patients with long-term follow-up data (6-120 months). It was found that 69.7% of patients achieved an excellent re-color effect and 18.4% achieved a good re-color effect. There were statistically significant differences in pigmentation between patients with stable disease course, vitiligo type, and lesion site. Overall, a significant positive correlation between the target area treatment ratio of varied lesions and the percentage of repigmentation was found. CMT is effective and well tolerated in the treatment of stable vitiligo. Various factors, especially the target area treatment ratio of varied lesions, should be carefully assessed before using CMT. As the target area treatment ratio of varied lesions could further improve the post-operative repigmentation other than type of vitiligo. This clinic trial was approved by Hangzhou Third People's Hospital (number 2023KA015, national clinical record number MR-33-23-034502).

[Impact on tyrosinase expression and export from endoplasmic reticulum by inhibition of 26S proteasome].

OBJECTIVE: To determine the impact on tyrosinase expression and export from endoplasmic reticulum by inhibition of 26S proteasome. METHODS: Western blot was used to detect 26S proteasome from 8 vitiligo patients and 4 healthy controls. Melanocytes were incubated with proteasome inhibitor (lactacystin) and further detected as follows: cell survival by MTT assay, proteasome activity with fluorescence, ultrastructure observation with electron microscope, co-localization of tyrosinase and calreticulin (endoplasmic reticulum marker) by confocal laser scanning microscopy and 26S proteasome and tyrosinase with Western blot. RESULTS: The 26S proteasome expression level from lesions of vitiligo (1.05 ± 0.40) was significantly lower than the donor sites (1.82 ± 0.88) and the healthy controls (1.88 ± 0.16) (P < 0.05). But no significant difference existed between the latter two groups (P > 0.05). Compared to the untreated group, a 12-h incubation of 10 µmol/L lactacystin showed inhibitory effects on melanocytes (0.999 ± 0.110 vs 1.372 ± 0.127, P < 0.05) and significantly decreased proteasome activity (0.234 ± 0.019 vs 1, P < 0.01). Expansion rate of endoplasmic reticulum in the lactacystin group (1.91 ± 0.17) was significantly higher than that of the untreated cells (1.17 ± 0.11) (P < 0.05). More tyrosinase co-localized with calreticulin in endoplasmic reticulum in lactacystin-treated cells was observed than that of the untreated group. Compared with the untreated group, significantly decreased levels of tyrosinase (146 ± 10 vs 269 ± 8, P < 0.01) and tyrosinase activity (0.159 ± 0.017 vs 0.221 ± 0.019, P < 0.01) were shown in the lactacystin group (P < 0.05). CONCLUSIONS: Significantly decrease of 26S proteasome is found in lesions of vitiligo patients. Inhibition of 26S proteasome may lead to expansion of endoplasmic reticulum of melanocytes, impact export of tyrosinase from melanocyte endoplasmic reticulum and expression of tyrosinase.

KG-MFEND: an efficient knowledge graph-based model for multi-domain fake news detection.

The widespread dissemination of fake news on social media brings adverse effects on the public and social development. Most existing techniques are limited to a single domain (e.g., medicine or politics) to identify fake news. However, many differences exist commonly across domains, such as word usage, which lead to those methods performing poorly in other domains. In the real world, social media releases millions of news pieces in diverse domains every day. Therefore, it is of significant practical importance to propose a fake news detection model that can be applied to multiple domains. In this paper, we propose a novel framework based on knowledge graphs (KG) for multi-domain fake news detection, named KG-MFEND. The model's performance is enhanced by improving the BERT and integrating external knowledge to alleviate domain differences at the word level. Specifically, we construct a new KG that encompasses multi-domain knowledge and injects entity triples to build a sentence tree to enrich the news background knowledge. To solve the problem of embedding space and knowledge noise, we use the soft position and visible matrix in knowledge embedding. To reduce the influence of label noise, we add label smoothing to the training. Extensive experiments are conducted on real Chinese datasets. And the results show that KG-MFEND has a strong generalization capability in single, mixed, and multiple domains and outperforms the current state-of-the-art methods for multi-domain fake news detection.

[Retracted] MicroRNA­9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1.

Following the publication of this article, a concerned reader drew to our attention that in Fig. 5C on p. 1704, showing histological images of mouse livers stained with H&E, unexpected areas of similarity were identified in terms of the staining patterns revealed within the data panels themselves. After having conducted an internal investigation, the Editor of Oncology Reports has reached the conclusion that the overlapping portions of data shown in this figure were unlikely to have arisen by coincidence. Therefore, on the grounds of a lack of confidence in the integrity of these data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused, and thanks the interested reader for drawing this matter to our attention. [Oncology Reports 37: 1698­1706, 2017; DOI: 10.3892/or.2017.5382].

[Corrigendum] The role of VIT1/FBXO11 in the regulation of apoptosis and tyrosinase export from endoplasmic reticulum in cultured melanocytes.

Following the publication of the above article, an interested reader drew to the authors' attention that the Transwell cell migration assay data shown in Fig. 4A appeared to be partly overlapping with data presented for experiments performed under different experimental conditions in Figs. 4D and E. The authors independently examined the figure and realized that inadvertent errors had been made during the assembly of Fig. 4; furthermore, owing to the time that has elapsed since this paper was published, the authors no longer had access to the original data. Accordingly, to further verify the conclusions reported in the study, the authors repeated these experiments, and the results obtained were found to be consistent with the original findings. The new version of Fig. 4 is shown below. The authors are grateful to the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 26: 57-65, 2010; DOI: 10.3892/ijmm_00000435].

A retrospective study of long term follow-up of 2283 vitiligo patients treated by autologous, non-cultured melanocyte-keratinocyte transplantation.

BACKGROUND: Autologous non-cultured melanocyte-keratinocyte transplantation (MKTP) can be used to treat stable vitiligo cases, but there were insufficient clinical data to evaluate its safety and efficacy. OBJECTIVE: To assess the influence of various factors on the therapeutic outcome of MKTP. METHOD: The single-center retrospective study included stable vitiligo patients who underwent MKTP between June 2009 and June 2018. Univariate and/or multivariable analysis were used to determine the factors affecting the outcome of repigmentation. RESULT: The study comprised 2283 patients who had long-term follow-up data (12-108months). Excellent repigmentation was achieved in 400/606 (66%),788/1341 (58.8%),437/684 (63.9%),18/24 (75%) patients with segmental vitiligo, pre-MKTP phototherapy, younger than 24 years, the lesion on the perineum and scrotum, respectively. However, the patients with a positive family history, Koebner phenomenon responded worse(χ2=29.417, P<0.001; χ2=107.397, P<0.001; respectively). Overall, a significant positive correlation between duration of stability and percentage of repigmentation was found (χ2=42.053, P<0. 001). CONCLUSION: MKTP is efficient and well tolerated for stable vitiligo treatment. Various factors such as duration of disease stability, vitiligo type, family history, site of lesion should be carefully assessed before using MKTP, as it would further improve the post-operative repigmentation.

[Expression of InnVit/FBXO11 in vitiligo and its role in tyrosinase export from endoplasmic reticulum].

OBJECTIVE: To investigate the roles of InnVit (FBX011) gene in melanocytes by detecting the expression of InnVit gene in vitiligo and analyzing the impact of InnVit gene on morphology of endoplasmic reticulum (ER) and the tyrosinase export from ER. METHODS: The lesion tissues and the donor tissues were collected from 10 vitiligo patients to examine the InnVit gene expression by immunohistochemistry. Synthesized specific siRNA and constructed plasmid P3XF-P120 were separately transfected into cells for the silence and over-expression of InnVit gene with lipofectamine(TM) 2000. The untreated cells were used as control. Morphology of ER of cells from the above three groups was observed under electron microscope. Co-localization of tyrosinase and calreticulin was identified by confocal laser scanning microscopy. InnVit, tyrosinase and calreticulin were examined by Western blot. RESULTS: In vitiligo patients, the expression of InnVit gene in the lesions was markedly lower than that in the donor tissues. The normal morphology of ER was found in the untreated and the plasmid groups whereas inflated ER was shown in siRNA group. And the relative inflation rate in siRNA group (1.97 +/- 0.48) was higher than that in the untreated group (1.28 +/- 0.09) and plasmid group (1.24 +/- 0.13) (both P = 0.001). In the untreated and the plasmid groups, tyrosinase was expressed beyond the scope marked by ER marker protein calreticulin partly, but co-localized with calreticulin in ER in the siRNA group. Western blot showed that, contrast to the untreated group (0.320 +/- 0.020), a lower expression level of InnVit in the siRNA group (0.030 +/- 0.004, P = 0.001) and a higher expression of InnVit in the plasmid group were shown (0.710 +/- 0.040, P = 0.001). No significant difference about the expression level of calreticulin was observed among the three groups (P > 0.05). As compared with the untreated group (0.350 +/- 0.030), a higher tyrosinase level in the siRNA group (1.040 +/- 0.060, P = 0.001) and in the plasmid group (0.720 +/- 0.030, P = 0.001) was found. And the former was higher than the latter (P = 0.001). CONCLUSION: A lower expression of InnVit is observed in the lesion tissues than in the donor tissues from vitiligo patients. The InnVit gene can have an impact on the morphology of ER and tyrosinase export from ER. And it may further affect the function of melanocytes.

MicroRNA-9 limits hepatic fibrosis by suppressing the activation and proliferation of hepatic stellate cells by directly targeting MRP1/ABCC1.

Liver fibrosis is a chronic liver disease characterized by the proliferation and activation of hepatic stellate cells (HSCs) and excessive deposition of extracellular matrix (ECM). Research suggests that microRNAs (miRNAs) are a new type of regulator of liver fibrosis. In the present study, we investigated the role of microRNA-9 (miR-9) in the process of liver fibrosis, as well as the underlying mechanism of action. Downregulated levels of miR-9 were found in fibrotic liver tissues and activated HSCs as detected by qRT-PCR; whereas, expression of multidrug resistance­associated protein 1 (MRP1/ABCC1) was upregulated in the fibrotic liver tissues and activated HSCs. CCK-8 and BrdU assays revealed that miR-9 reduced the proliferative ability of the HSCs. In addition, expression levels of ECM-related genes (α-SMA, Col-1 and Timp-1), which are markers of HSC activation, were downregulated by miR-9. Conversely, an miR-9 inhibitor promoted cell proliferation and HSC activation. In addition, a luciferase reporter assay indicated that miR-9 targets the 3'-untranslated region (3'-UTR) of MRP1 and causes a significant decrease in MRP1. miR-9 inhibited the activation of the Hedgehog (Hh) pathway and the expression of MRP1, while this suppression was rescued by the overexpression of MRP1. Finally, a CCl4-induced mouse model of liver fibrosis was used to investigate the effects of miR-9 on liver fibrosis in vivo. The results showed that miR-9 abrogated hepatic fibrosis by suppressing the expression of MRP1 in CCl4-induced liver fibrotic mice. In conclusion, the present study demonstrated that miR-9 suppresses the proliferation and activation of HSCs through the Hh pathway by targeting MRP1, which suggests that miR-9 has therapeutic potential for liver fibrosis.

Successful Repigmentation of Vitiligo after Allogeneic Bone Marrow Transplantation for Hodgkin's Lymphoma by Autologous Noncultured Melanocyte-keratinocyte Transplantation.

The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin's lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation.

Blister roof grafting, cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in treating stable vitiligo: A mutual self-control study.

OBJECTIVES: To compare the efficacy of blister roof grafting (BG), cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of stable vitiligo. METHODS: In each person of 83 vitiligo patients one vitiligo macule was selected and divided in three areas for separate treatment with BG, CMT and NCES in the same session. The results were evaluated 12-month post-surgery for the extent of repigmentation and color match. RESULTS: A satisfactory result (>50% repigmentation) was achieved in 92%, 82% and 81% of the 83 patients with the BG, CMT and NCES methods, respectively. Significant differences between the BG and CMT groups (p = 0.038), and between BG and NCES groups (p = 0.017) were observed, but not between the CMT and NCES groups (p = 0.986). The extent of repigmentation on the head neck and trunk was superior to that of the extremities by all the three methods. A difference in the time of onset of repigmentation was observed, with repigmentation first appearing after 10 days, 20-30 days and >30 days in the BG, CMT and NCES groups, respectively. CONCLUSIONS: All the three methods are safe and effective to treat vitiligo. Future studies with larger groups are warranted to confirm our results.

Quercetin attenuates the effects of H2O2 on endoplasmic reticulum morphology and tyrosinase export from the endoplasmic reticulum in melanocytes.

Swollen endoplasmic reticulum (ER) is commonly observed in the melanocytes of vitiligo patients; however, the cause and proteins involved in this remain to be elucidated. Oxidative stress has been reported to be involved in the pathogenesis of vitiligo and previous studies have demonstrated that hydrogen peroxide (H2O2) induced melanocyte apoptosis, whereas quercetin exhibited cytoprotective activities against the effects of H2O2. The aim of the present study was to further investigate the role of H2O2 in the ER of melanocytes as well as its role in the export of tyrosinase from ER; in addition, the present study aimed to determine the mechanism by which quercetin protects against the effects of H2O2. The results demonstrated that melanocyte cells treated with H2O2 presented with swollen ER; however, a normal ER configuration was observed in untreated cells as well as quercetin/H2O2­treated cells. Furthermore, H2O2 inhibited tyrosinase export from the ER and decreased expression levels of tyrosinase; however, quercetin was found to attenuate the effects induced by H2O2. In conclusion, the results of the present study confirmed the hypothesis that H2O2 induced ER dilation and hindered functional tyrosinase export from the ER of melanocytes. It was also found that quercetin significantly weakened these effects mediated by H2O2, therefore it may have the potential for use in the treatment of vitiligo.

Dermal mesenchymal stem cells (DMSCs) inhibit skin-homing CD8+ T cell activity, a determining factor of vitiligo patients' autologous melanocytes transplantation efficiency.

We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients' autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy.

Transferable crosslinked chitosan membranes for human melanocyte culture.

Development of transferable biocompatible membranes, which can be used for melanocyte culture and transplantation, is considered a feasible approach to increase the success rate for vitiliginous treatment. In this study, a crosslinked chitosan membrane (CCM) was produced via physical crosslinking of chitosan with sodium sulfate. The physical and mechanical properties as well as growth and phenotype expression of melanocytes on the CCM were investigated. The CCM supported growth and proliferation of melanocytes with the existence of melanin granules in the cytoplasm. The melanocytes remained active after transplantation. The CCM absorbed water approximately doubled from its original weight and permitted ∼2400 g/m² per day of water vapor transmission, suggesting that the CCM can function as an efficient wound dressing. Dynamic mechanical and tensile measurement results showed that the CCM possessed favorable wet strength for cell culture, separation, transfer, and transplantation application. This transferable CCM has the potential to be applied for vitiligo treatment.

Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes.

Niacin and its related derivatives have been shown to have effects on cellular activities. However, the molecular mechanism of its reduced immunosuppressive effects and photoprotective effects remains unclear. In this study, we investigated the molecular mechanism of the photoprotective effect of niacin in ultraviolet (UV)-irradiated human skin keratinocytes (HaCaT cells). We found that niacin effectively suppressed the UV-induced cell death and cell apoptosis of HaCaT cells. Existing data have shown that AKT activation is involved in the cell survival process. Yet, the potential mechanism of niacin in protection against UV-induced skin damage has thus far not fully been eluvidated. We observed that niacin pretreatment enhances UV induced activation of AKT (Ser473 phosphorylation) as well as that of the downstream signal mTOR (S6 and 4E-BP1 phosphorylation). The PI3K/AKT inhibitor, LY294002, and the mTOR inhibitor, rapamycin, largely neutralized the protective effects of niacin, suggesting that AKT and downstream signaling mTOR/S6 activation are necessary for the niacin-induced protective effects against UV-induced cell death and cell apoptosis. Collectively, our data suggest that niacin may be utilized to prevent UV-induced skin damage and provide a novel mechanism of its photoprotective effects against the UV radiation of sunlight by modulating both AKT and downstream mTOR signaling pathways.