Human C15orf39 Inhibits Inflammatory Response via PRMT2 in Human Microglial HMC3 Cell Line.

Microglia-mediated inflammatory response is one key cause of many central nervous system diseases, like Alzheimer's disease. We hypothesized that a novel C15orf39 (MAPK1 substrate) plays a critical role in the microglial inflammatory response. To confirm this hypothesis, we used lipopolysaccharide (LPS)-and interferon-gamma (IFN-γ)-induced human microglia HMC3 cells as a representative indicator of the microglial in vitro inflammatory response. We found that C15orf39 was down-regulated when interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) expression increased in LPS/IFN-γ-stimulated HMC3 cells. Once C15orf39 was overexpressed, IL-6 and TNFα expression were reduced in LPS/IFN-γ-stimulated HMC3 cells. In contrast, C15orf39 knockdown promoted IL-6 and TNFα expression in LPS/IFN-γ-stimulated HMC3 cells. These results suggest that C15orf39 is a suppressive factor in the microglial inflammatory response. Mechanistically, C15orf39 interacts with the cytoplasmic protein arginine methyltransferase 2 (PRMT2). Thus, we termed C15orf39 a PRMT2 interaction protein (PRMT2 IP). Furthermore, the interaction of C15orf39 and PRMT2 suppressed the activation of NF-κB signaling via the PRMT2-IκBα signaling axis, which then led to a reduction in transcription of the inflammatory factors IL6 and TNF-α. Under inflammatory conditions, NF-κBp65 was found to be activated and to suppress C15orf39 promoter activation, after which it canceled the suppressive effect of the C15orf39-PRMT2-IκBα signaling axis on IL-6 and TNFα transcriptional expression. In conclusion, our findings demonstrate that in a steady condition, the interaction of C15orf39 and PRMT2 stabilizes IκBα to inhibit IL-6 and TNFα expression by suppressing NF-κB signaling, which reversely suppresses C15orf39 transcription to enhance IL-6 and TNFα expression in the microglial inflammatory condition. Our study provides a clue as to the role of C15orf39 in microglia-mediated inflammation, suggesting the potential therapeutic efficacy of C15orf39 in some central nervous system diseases.

Nitric Oxide Ameliorates the Effects of Hypoxia in Mice by Regulating Oxygen Transport by Hemoglobin.

Xiaoying Zhou, Wenting Su, Quanwei Bao, Yu Cui, Xiaoxu Li, Yidong Yang, Chengzhong Yang, Chengyuan Wang, Li Jiao, Dewei Chen, and Jian Huang. Nitric oxide ameliorates the effects of hypoxia in mice by regulating oxygen transport by hemoglobin. High Alt Med Biol. 25:174-185, 2024.-Hypoxia is a common pathological and physiological phenomenon in ischemia, cancer, and strenuous exercise. Nitric oxide (NO) acts as an endothelium-derived relaxing factor in hypoxic vasodilation and serves as an allosteric regulator of hemoglobin (Hb). However, the ultimate effects of NO on the hematological system in vivo remain unknown, especially in extreme environmental hypoxia. Whether NO regulation of the structure of Hb improves oxygen transport remains unclear. Hence, we examined whether NO altered the oxygen affinity of Hb (Hb-O2 affinity) to protect extremely hypoxic mice. Mice were exposed to severe hypoxia with various concentrations of NO, and the survival time, exercise capacity, and other physical indexes were recorded. The survival time was prolonged in the 5 ppm NO (6.09 ± 1.29 minutes) and 10 ppm NO (6.39 ± 1.58 minutes) groups compared with the 0 ppm group (4.98 ± 1.23 minutes). Hypoxia of the brain was relieved, and the exercise exhaustion time was prolonged when mice inhaled 20 ppm NO (24.70 ± 6.87 minutes vs. 20.23 ± 6.51 minutes). In addition, the differences in arterial oxygen saturation (SO2%) (49.64 ± 7.29% vs. 42.90 ± 4.30%) and arteriovenous SO2% difference (25.14 ± 8.95% vs. 18.10 ± 6.90%) obviously increased. In ex vivo experiments, the oxygen equilibrium curve (OEC) left shifted as P50 decreased from 43.77 ± 2.49 mmHg (0 ppm NO) to 40.97 ± 1.40 mmHg (100 ppm NO) and 38.36 ± 2.78 mmHg (200 ppm NO). Furthermore, the Bohr effect of Hb was enhanced by the introduction of 200 ppm NO (-0.72 ± 0.062 vs.-0.65 ± 0.051), possibly allowing Hb to more easily offload oxygen in tissue at lower pH. The crystal structure reveals a greater distance between Asp94ß-His146ß in nitrosyl -Hb(NO-Hb), NO-HbßCSO93, and S-NitrosoHb(SNO-Hb) compared to tense Hb(T-Hb, 3.7 Å, 4.3 Å, and 5.8 Å respectively, versus 3.5 Å for T-Hb). Moreover, hydrogen bonds were less likely to form, representing a key limitation of relaxed Hb (R-Hb). Upon NO interaction with Hb, hydrogen bonds and salt bridges were less favored, facilitating relaxation. We speculated that NO ameliorated the effects of hypoxia in mice by promoting erythrocyte oxygen loading in the lung and offloading in tissues.

Fatty acid metabolism-related molecular subtypes and a novel model for predicting prognosis in bladder cancer patients.

This study aims to develop fatty acid metabolism-related molecular subtypes and construct a fatty acid metabolism-related novel model for bladder cancer (BCa) by bioinformatic profiling. Genome RNA-seq expression data of BCa samples from the TCGA database and GEO database were downloaded. We then conducted consensus clustering analysis to identify fatty acid metabolism-related molecular subtypes for BCa. Univariate and multivariate Cox regression analysis were performed to identify a novel prognostic fatty acid metabolism-related prognostic model for BCa. Finally, we identified a total of three fatty acid metabolismrelated molecular subtypes for BCa. These three molecular subtypes have significantly different clinical characteristics, PD-L1 expression levels, and tumor microenvironments. Also, we developed a novel fatty acid metabolism-related prognostic model. Patients with low-risk score have significantly preferable overall survival compared with those with high-risk score in the training, testing, and validating cohorts. The area under the ROC curve (AUC) for overall survival prediction was 0.746, 0.681, and 0.680 in the training, testing and validating cohorts, respectively. This model was mainly suitable for male, older, high-grade, cluster 2-3, any TCGA stage, any N-stage, and any T-stage patients. Besides, we selected FASN as a hub gene for BCa and further qRT-PCR validation was successfully conducted. In conclusion, we developed and successfully validated a novel fatty acid metabolism-related prognostic model for predicting outcome for BCa patients.

Polyporus umbellatus polysaccharide iron-based nanocomposite for synergistic M1 polarization of TAMs and combinational anti-breast cancer therapy.

M1 polarization of tumor-associated macrophages (TAMs) is a promising approach to breaking through therapeutic barriers imposed by the immunosuppressive tumor microenvironment (TME). As a clinically-used immunopotentiator for cancer patients after chemotherapies; however, the immunomodulatory mechanism and potential of polyporus polysaccharide (PPS) remains unclear. Here, we present mannose-decorated PPS-loaded superparamagnetic iron-based nanocomposites (Man/PPS-SPIONs) for synergistic M1 polarization of TAMs and consequent combinational anti-breast cancer therapy. Once internalized by M2-like TAMs, PPS released from Man/PPS-SPIONs induces the M1 polarization via IFN-γ secretion and downstream NF-κB pathway activating. The SPIONs within the nanocomposites mediate a Fenton reaction, producing OH· and activating the subsequent NF-κB/MAPK pathway, further facilitating the M1 polarization. The Man/PPS-SPIONs thereby establish a positive feedback loop of M1 polarization driven by the "IFN-γ-Fenton-NF-κB/MAPK" multi-pathway, leading to a series of anti-tumoral immunologic responses in the TME and holding promising potential in combinational anticancer therapies. Our study offers a new strategy to amplify TME engineering by combinational natural carbohydrate polymers and iron-based materials.

Effervescent cannabidiol solid dispersion-doped dissolving microneedles for boosted melanoma therapy via the "TRPV1-NFATc1-ATF3" pathway and tumor microenvironment engineering.

BACKGROUND: Conventional dissolving microneedles (DMNs) face significant challenges in anti-melanoma therapy due to the lack of active thrust to achieve efficient transdermal drug delivery and intra-tumoral penetration. METHODS: In this study, the effervescent cannabidiol solid dispersion-doped dissolving microneedles (Ef/CBD-SD@DMNs) composed of the combined effervescent components (CaCO3 & NaHCO3) and CBD-based solid dispersion (CBD-SD) were facilely fabricated by the "one-step micro-molding" method for boosted transdermal and tumoral delivery of cannabidiol (CBD). RESULTS: Upon pressing into the skin, Ef/CBD-SD@DMNs rapidly produce CO2 bubbles through proton elimination, significantly enhancing the skin permeation and tumoral penetration of CBD. Once reaching the tumors, Ef/CBD-SD@DMNs can activate transient receptor potential vanilloid 1 (TRPV1) to increase Ca2+ influx and inhibit the downstream NFATc1-ATF3 signal to induce cell apoptosis. Additionally, Ef/CBD-SD@DMNs raise intra-tumoral pH environment to trigger the engineering of the tumor microenvironment (TME), including the M1 polarization of tumor-associated macrophages (TAMs) and increase of T cells infiltration. The introduction of Ca2+ can not only amplify the effervescent effect but also provide sufficient Ca2+ with CBD to potentiate the anti-melanoma efficacy. Such a "one stone, two birds" strategy combines the advantages of effervescent effects on transdermal delivery and TME regulation, creating favorable therapeutic conditions for CBD to obtain stronger inhibition of melanoma growth in vitro and in vivo. CONCLUSIONS: This study holds promising potential in the transdermal delivery of CBD for melanoma therapy and offers a facile tool for transdermal therapies of skin tumors.

Tropospheric formaldehyde levels infer ambient formaldehyde-induced brain diseases and global burden in China, 2013-2019.

Although air pollutions cause human diseases, no epidemiological study has investigated the effect of exposure to air pollutants on brain diseases in the general population. Our objective was to examine the association between tropospheric airborne pollutants and human health risk and global burden, especially, attributable to indoor formaldehyde (FA) pollution in China. The data of tropospheric pollutants, such as: CO, NO, O3, PM2.5 or PM10, SO2, and FA in China, 2013-2019, which were derived from the database of satellite remote-sensing, were first calculated and then analyzed them according to satellite cloud pictures. The rate of prevalence, incidence, deaths, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) of the Chinese population was obtained from the Global Burden of Diseases (GBD 2010). A linear regression analysis was used to evaluate the relationship between tropospheric FA concentrations and GBD indexes of human brain diseases, the numbers of fire plot, the average summer temperature, population density and car sales in China from 2013 to 2019. Our results showed that the levels of tropospheric FA could reflect the degree of indoor air FA pollution on a nationwide scale in China; in particular, only tropospheric FA exhibited a positive correlation with the rates of both prevalence and YLDs in brain diseases including: Alzheimer's disease (AD) and brain cancer, but not in Parkinson's disease and depression. In particular, the spatial-temporal changes in tropospheric FA levels were consistent with the geographical distribution of FA exposure-induced AD and brain cancer in both sex old adults with age (60-89). In addition, summer average temperature, car sales and population density were positively correlated with tropospheric FA levels in China, 2013-2019. Hence, mapping of tropospheric pollutants could be used for air quality monitoring and health risk assessment.

Mendelian randomization study on causal association of IL-6 signaling with pulmonary arterial hypertension.

BACKGROUND: A recent Mendelian randomization (MR) did not support an effect of the lead interleukin-6 receptor (IL-6 R) variant on risk of pulmonary arterial hypertension (PAH). Thus, we used two sets of genetic instrumental variants (IVs) and publicly available PAH genome-wide association studies (GWAS) to reassess the genetic causal link between IL-6 signaling and PAH. METHODS: Six independent IL-6 signaling and 34 independent soluble IL-6 receptor (sIL-6 R) genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. RESULTS: We found that as IL-6 signaling genetically increased, the risk of PAH reduced using IVW (odds ratio [OR] = 0.023, 95% confidence interval [CI]: 0.0013-0.393; p = .0093) and weighted median (OR = 0.033, 95% CI: 0.0024-0.467; p = .0116). Otherwise, as sIL-6 R genetically increased, the risk of PAH increased using IVW (OR = 1.34, 95% CI: 1.16-1.56; p = .0001), weighted median (OR = 1.36, 95% CI: 1.10-1.68; p = .005), MR-Egger (OR = 1.43, 95% CI: 1.05-1.94; p = .03), and weighted mode (OR = 1.35, 95% CI for OR: 1.12-1.63; p = .0035). CONCLUSION: Our analysis suggested the causal link between genetically increased sIL-6 R and increased risk of PAH and between genetically increased IL-6 signaling and reduced risk of PAH. Thus, higher sIL-6 R levels may be a risk factor for patients with PAH, whereas higher IL-6 signaling may be a protective factor for patients with PAH.

Ki-67 index of 5% could better predict the clinical prognosis of well-differentiated pancreatic neuroendocrine tumours.

BACKGROUND: The pathological classification of well-differentiated pancreatic neuroendocrine tumour (pNET) is based largely upon Ki-67 index. However, current controversies abound about the classification of pNETG1/pNETG2. PATIENTS AND METHODS: Clinicopathological data were retrospectively analysed for 153 pNETG1/pNETG2 patients hospitalized at China-Japan Friendship Hospital. The critical values of pNETG1/pNETG2 were examined by using the area under the receiver operating characteristic curve and survival analysis was used to compare the clinical prognosis of pNETG1/G2. RESULTS: Among them, 52.3% were males. The median age was 49 (18-81) years and the clinical types were pNETG1 (n = 38) and pNETG2 (n = 115). According to the receiver operating characteristic curve, the optimal cut-off value was 5.5% for classifying pNETG1/pNETG2. Significant differences between pNETG1 (n = 101) and pNETG2 (n = 52) existed in overall survival (P = 0.001) and disease-free survival (P = 0.013) when Ki-67 index was 5%. Yet no significant differences existed in overall survival (P = 0.378) or disease-free survival (P = 0.091) between pNETG1 and pNETG2 when Ki-67 index was 3%. Furthermore, multivariate analysis indicated that the revised pathological grade was an independent risk factor for mortality and post-operative recurrence of pNET patients (P = 0.003 and 0.014; hazard ratio (HR) = 4.005 and 2.553). CONCLUSION: Thus, differentiating pNETG1/pNETG2 with Ki-67 index (5%) is proposed as the cut-off value and a new Ki-67 index (5%) is a better predictor of pNET mortality and post-operative recurrence than Ki-67 index (3%).

Gm40600 promotes CD4+ T-cell responses by interacting with Ahnak.

It is important to characterize novel proteins involved in T- and B-cell responses. Our previous study demonstrated that a novel protein, Mus musculus Gm40600, reduced the proliferation of Mus musculus plasmablast (PB)-like SP 2/0 cells and B-cell responses induced in vitro by LPS. In the present study, we revealed that Gm40600 directly promoted CD4+ T-cell responses to indirectly up-regulate B-cell responses. Importantly, we found that CD4+ T-cell responses, including T-cell activation and differentiation and cytokine production, were increased in Gm40600 transgenic (Tg) mice and were reduced in Gm40600 knockout (KO) mice. Finally, we demonstrated that Gm40600 promoted the Ahnak-mediated calcium signalling pathway by interacting with Ahnak to maintain a cytoplasmic lateral location of Ahnak in CD4+ T cells. Collectively, our data suggest that Gm40600 promotes CD4+ T-cell activation to up-regulate the B-cell response via interacting with Ahnak to promote the calcium signalling pathway. The results suggest that targeting Gm40600 may be a means to control CD4+ T-cell-related diseases.

Chemically Modified SDF-1α mRNA Promotes Random Flap Survival by Activating the SDF-1α/CXCR4 Axis in Rats.

Random skin flaps are frequently applied in plastic and reconstructive surgery for patients suffering from soft tissue defects caused by congenital deformities, trauma and tumor resection. However, ischemia and necrosis in distal parts of random skin flaps remains a common challenge that limits the clinical application of this procedure. Recently, chemically modified mRNA (modRNA) was found to have great therapeutic potential. Here, we explored the potential of fibroblasts engineered to express modified mRNAs encoding the stromal cell-derived factor-1α (SDF-1α) to improve vascularization and survival of therapeutic random skin flaps. Our study showed that fibroblasts pre-treated with SDF-1α modRNA have the potential to salvage ischemic skin flaps. Through a detailed analysis, we revealed that a fibroblast SDF-1α modRNA combinatorial treatment dramatically reduced tissue necrosis and significantly promoted neovascularization in random skin flaps compared to that in the control and vehicle groups. Moreover, SDF-1α modRNA transcription in fibroblasts promoted activation of the SDF-1α/CXCR4 pathway, with concomitant inactivation of the MEK/ERK, PI3K/AKT, and JAK2/STAT3 signaling pathways, indicating a possible correlation with cell proliferation and migration. Therefore, fibroblast-mediated SDF-1α modRNA expression represents a promising strategy for random skin flap regeneration.

A FRET Based Two-Photon Fluorescent Probe for Visualizing Mitochondrial Thiols of Living Cells and Tissues.

Glutathione (GSH) is the main component of the mitochondrial thiol pool and plays key roles in the biological processes. Many evidences have suggested that cysteine and homocysteine also exist in mitochondria and are interrelated with GSH in biological systems. The fluctuation of the levels of mitochondrial thiols has been linked to many diseases and cells' dysfunction. Therefore, the monitoring of mitochondrial thiol status is of great significance for clinical studies. We report here a novel fluorescence resonance energy transfer based two-photon probe MT-1 for mitochondrial thiols detection. MT-1 was constructed by integrating the naphthalimide moiety (donor) and rhodamine B (accepter and targeting group) through a newly designed linker. MT-1 shows a fast response, high selectivity, and sensitivity to thiols, as well as a low limit of detection. The two-photon property of MT-1 allows the direct visualization of thiols in live cells and tissues by two-photon microscopy. MT-1 can serve as an effective tool to unravel the diverse biological functions of mitochondrial thiols in living systems.

Scutellarin Attenuates the IL-1ß-Induced Inflammation in Mouse Chondrocytes and Prevents Osteoarthritic Progression.

Osteoarthritis (OA) is a chronic degenerative disease wherein the articular cartilage exhibits inflammation and degradation. Scutellarin (SCU) is a flavonoid glycoside with a range of pharmacological activities, as shown in previous studies demonstrating its anti-inflammatory activity. How SCU impacts the progression of OA, however, has not been explored to date. Herein, we assessed the impact of SCU on murine chondrocytes in an OA model system. In in vitro assays, we measured chondrocyte expression of key OA-associated factors such as matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) via qRT-PCR and Western blotting, the expression of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E2 (PGE2) were detected by qRT-PCR. Our results showed that the downregulation of MMP-13, ADAMTS-5, COX-2, and iNOS expression by SCU and the overproduction of IL-6, TNF-α, and PGE2 induced by IL-1ß were all inhibited by SCU in a concentration-dependent manner. Moreover, SCU was able to reverse aggrecan and collagen II degradation and nuclear factor-κB (NF-κB) and nuclear factor erythroid-derived 2-like 2 (Nrf2) signaling pathway activation both in vivo and in vitro. We further used a destabilization of the medial meniscus (DMM) murine model of OA to explore the therapeutic benefits of SCU in vivo. Together, our findings suggest SCU to be a potentially valuable therapeutic agent useful for treating OA.

Identification of key DNA methylation-driven genes in prostate adenocarcinoma: an integrative analysis of TCGA methylation data.

BACKGROUND: Prostate cancer (PCa) remains the second leading cause of deaths due to cancer in the United States in men. The aim of this study was to perform an integrative epigenetic analysis of prostate adenocarcinoma to explore the epigenetic abnormalities involved in the development and progression of prostate adenocarcinoma. The key DNA methylation-driven genes were also identified. METHODS: Methylation and RNA-seq data were downloaded for The Cancer Genome Atlas (TCGA). Methylation and gene expression data from TCGA were incorporated and analyzed using MethylMix package. Methylation data from the Gene Expression Omnibus (GEO) were assessed by R package limma to obtain differentially methylated genes. Pathway analysis was performed on genes identified by MethylMix criteria using ConsensusPathDB. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also applied for the identification of pathways in which DNA methylation-driven genes significantly enriched. The protein-protein interaction (PPI) network and module analysis in Cytoscape software were used to find the hub genes. Two methylation profile (GSE112047 and GSE76938) datasets were utilized to validate screened hub genes. Immunohistochemistry of these hub genes were evaluated by the Human Protein Atlas. RESULTS: A total of 553 samples in TCGA database, 32 samples in GSE112047 and 136 samples in GSE76938 were included in this study. There were a total of 266 differentially methylated genes were identified by MethylMix. Plus, a total of 369 differentially methylated genes and 594 differentially methylated genes were identified by the R package limma in GSE112047 and GSE76938, respectively. GO term enrichment analysis suggested that DNA methylation-driven genes significantly enriched in oxidation-reduction process, extracellular exosome, electron carrier activity, response to reactive oxygen species, and aldehyde dehydrogenase [NAD(P)+] activity. KEGG pathway analysis found DNA methylation-driven genes significantly enriched in five pathways including drug metabolism-cytochrome P450, phenylalanine metabolism, histidine metabolism, glutathione metabolism, and tyrosine metabolism. The validated hub genes were MAOB and RTP4. CONCLUSIONS: Methylated hub genes, including MAOB and RTP4, can be regarded as novel biomarkers for accurate PCa diagnosis and treatment. Further studies are needed to draw more attention to the roles of these hub genes in the occurrence and development of PCa.

Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases.

Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.

Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review.

BACKGROUND: We have previously proved that treatment of thick/deep infantile hemangiomas (IHs) with a long-pulse Alexandrite laser was clinically effective and safe. This article aims to investigate the efficiency of long-pulse Alexandrite laser use in treating thick and high-risk IHs located in particular anatomic areas and provides some new data on this issue. CASE SUMMARY: A two-month-old girl with a thick and high-risk IH covering most of the right labia majora was examined in this study. The infant received four treatment sessions at 4- to 6-wk intervals with a long-pulse Alexandrite laser with settings as follows: 3 ms pulse duration, 8 mm spot size, 45 to 50 J/cm2 fluences, and dynamic cooling device (DCD) spray duration of 90 ms with a delay of 80 ms. Following each of the four treatment sessions, the IH showed a remarkable reduction in thickness and size without any sign of relapse. Ten months after the last treatment, the IH had completely regressed without adverse effects. During the laser treatment, no severe side effects were observed; blistering occurred only immediately after treatment and then scabbed over the next day, gradually improving in the following days. CONCLUSION: Long-pulse Alexandrite laser treatment may be considered one of the first-line noninvasive therapeutic options for the treatment of thick IH.

Overexpression of interleukin-23 and interleukin-17 in the lesion of pemphigus vulgaris: a preliminary study.

IL-23/IL-17 axis has been identified as major factor involved in the pathogenesis of several autoimmune diseases; yet its pathogenetic role in pemphigus vulgaris (PV) remains controversial. The aim of this research was to investigate the potential role of IL-23/IL-17 axis in the immunopathogenesis of PV, and correlation between IL-23+ cells and IL-17+ cells was also evaluated. For this purpose, ten patients with PV, three patients with pemphigus foliaceus (PF), and six healthy individuals were allocated to this research. The lesional skin biopsy specimens were obtained before treatment. Then immunofluorescence staining was performed to analyze the expression of IL-23 and IL-17 in the PV/PF patients and the healthy individuals. The results showed that the numbers of IL-23+ and IL-17+ cells were significantly higher in PV lesions, compared to PF lesions and normal control skins, respectively (all P < 0.05). Moreover, the correlation between IL-23+ cells and IL-17+ cells was significant (r = 0.7546; P < 0.05). Taken together, our results provided evidence that the IL-23/IL-17 axis may play a crucial role in the immunopathogenesis of PV and may serve as novel therapeutic target for PV.

Beneficial effects of early treatment of infantile hemangiomas with a long-pulse Alexandrite laser.

BACKGROUND AND OBJECTIVE: There is an increasing interest in treating vascular lesions with a long-pulse Alexandrite laser. However, it is difficult to search information in the literature about infantile hemangiomas (IH) treated with long-pulse Alexandrite laser. This article aims to determine whether 755 nm long-pulse Alexandrite laser is effective and safe for early intervention of IH and provides some new data on this issue. MATERIALS AND METHODS: This is a retrospective study of 48 infants with IH treated with long-pulse Alexandrite laser during a 1.5-year period. Patients received a series of 1-7 treatment sessions with long-pulse Alexandrite laser at settings of 3 milliseconds pulse duration, 6-8 mm spot, 45-70 J/cm(2) fluences, and with dynamic cooling device (DCD) spray duration of 90 milliseconds and delay of 80 milliseconds, given at 4- to 6-week intervals. RESULTS: This study demonstrated that IH responded favorably to the treatment of a long-pulse Alexandrite laser while accompany with relatively few complications. The difference between the original untreated and post-treatment scores of all IH and two subgroups were statistically significant, respectively (P < 0.01). The difference of the degree of improvement between the two subgroups was not significant (P > 0.05). It was observed that IH on the trunk and extremities improved more effectively and more quickly than those on the face, neck, and perineum. Besides, age at the first treatment, the sex of the patients and the presence of proliferation were not significantly correlated with the degree of improvement. Adverse effects were seen in 11 patients (22.91%): blistering (n = 9), marked edema and erosion without subsequent residual scarring (n = 1), and hypopigmentation (n = 1), which improved gradually with time. Fortunately, there was no incidence of scarring or ulceration in this case series of IH. CONCLUSIONS: It was clinically effective and safe for early treatment of IH, including the thick/deep ones, with a long-pulse Alexandrite laser, which indicated be able to reduce the possibility that the IH will reach its full size. In this way it can prevent several complications connected to the rapid proliferation of IH.