Retraction Notice to: miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

[This retracts the article DOI: 10.1016/j.omto.2020.03.009.].

Esculentoside A ameliorates DNCB-induced atopic dermatitis by suppressing the ROS-NLRP3 axis via activating the Nrf2 pathway.

Atopic dermatitis (AD) is a chronic inflammatory skin condition with a high prevalence. Inflammation and oxidative stress are strongly associated with AD progression. Esculentoside A (EsA) inhibits inflammation and oxidative stress in various diseases. However, whether EsA mitigates AD by suppressing inflammation and oxidative stress remains unknown. A mouse model of AD was constructed by the induction of 1-chloro-2,4-dinitrochlorobenzene (DNCB). The mechanism of EsA and its effects on AD symptoms, pathology, inflammation and oxidative stress were investigated through histopathological staining, enzyme-linked immunosorbent assay, blood cells analysis, colorimetric measurement and western blot analysis. EsA improved the clinical symptoms and increased clinical skin scores in AD mice. Skin thickening of the epidermis and dermal tissues and the mast cell numbers in AD mice were reduced with the EsA treatment. EsA decreased the relative mRNA level of thymic stromal lymphopoietin, interleukin (IL)-4, IL-5 and IL-13; the serum concentrations of immunoglobulin E (IgE) and IL-6; and the numbers of white blood cells (WBC) and WBC subtypes, including basophil, lymphocytes, eosinophil, neutrophil and monocytes in DNCB-induced mice. DNCB caused higher levels of oxidative stress, which was reversed with the administration of EsA. Mechanically, EsA upregulated the expression of Nrf2 but downregulated the level of NLRP3 inflammasome in AD mice. The inhibitor of Nrf2 significantly recovered the EsA-induced changes in the NLRP3 inflammasome proteins in DNCB-treated mice. Therefore, EsA improved the clinical and pathological symptoms, inflammation and oxidative stress experienced by DNCB-induced mice and was involved in the inactivation of NLRP3 inflammasome by activating Nrf2.

Timing of systemic resistance induced by local exogenous ABA application within clonal network of stoloniferous herb Centella asiatica subjected to low water availability.

Resistance traits of plants can be activated both at the damaged site and undamaged parts. Systemic resistance induced by local exogenous abscisic acid (ABA) application alleviated negative effect of low water availability on growth performance of clonal plant. However, timing of systemic resistance was poorly understood. Timing of systemic resistance refers to its activation and decay time within clonal network. Clonal fragment of Centella asiatica with four successive ramets (including first-oldest, second-older, third-old and fourth-young ramets) subjected to low water availability (20% soil moisture content) was used to explore effects of local exogenous ABA application on the timing of resistance activation and decay. Systemic resistance activated by local exogenous ABA application after 4 days remained at least 28 days. Compared with control, biomass accumulation of whole clonal fragment, root biomass and ratio of belowground to aboveground biomass significantly increased by local exogenous ABA application after 28 days. It is suggested that rapid activation and delay of resistance response induced by local exogenous ABA application within clonal network may improve fitness of clonal plant subjected to abiotic stress.

Serum Irisin: A Potential Diagnostic Marker for Insulin Resistance in Acne Vulgaris.

Background: Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous unit. Many factors are involved in the occurrence of acne. It has been confirmed that some adipokines play an important role in the development of AV. Irisin is a novel adipokine, which is highly expressed in skeletal muscle, liver, and fat. It improves insulin resistance (IR) by inducing the browning of white adipose tissue, increasing heat production and energy expenditure. Objective: The purpose of this study was to investigate the role of serum irisin as an adipokine to explore its function in the pathogenesis of AV and its correlation with IR, and whether it can be used as a potential biomarker of insulin sensitivity. Although the hyperinsulinemic-euglycemic clamp remains the gold standard for accurate determination of IR, it cannot be performed routinely. Various alternative simpler measures have been used, the most common being homeostasis model assessment. However, these metrics are limited by their accuracy, cost, and blood collection requirements.[1] Therefore, an effective and feasible serum biomarker is an attractive and relatively straightforward method, which may provide clinicians with a more accurate and simple method for the prediction and diagnosis of IR. IR can often be detected before other symptoms appear, so establishing an early diagnosis method will allow for the appropriate treatment of patients before the disease develops. Patients and Methods: The study included 171 subjects; 115 patients with newly diagnosed AV and 56 apparently healthy subjects. The contents of irisin and interleukin-1 alpha in serum were determined by enzyme-linked immunosorbent assay. The IR index was calculated by the homeostasis model. Results: Serum irisin levels in AV patients and control group were (24.0 ± 11.3) and (104.3 ± 27.0) ng/dl, respectively, which were significantly lower than those in control group (P < 0.001). Serum irisin was negatively correlated with IR (r = -0.711, P 0.001). The sensitivity of irisin was 100.0%, the specificity was 92.8%, and the cutoff point was 53.32. The decrease of serum irisin level could predict the patients with IR in acne. Conclusion: Serum irisin levels in AV patients were significantly decreased. Serum irisin showed acceptable performance criteria in the diagnosis of AV with IR. Serum irisin seems to be a good diagnostic and prognostic marker for IR. Further multi-center studies are needed to confirm this link, which could pave the way for new treatment options.

The c.323 G>C mutation in LORICRIN causes new-found late-onset autosomal dominant loricrin keratoderma in a Chinese Han Pedigree.

BACKGROUND: Loricrin keratoderma is a rare early-onset autosomal dominant skin disorder. At present, no clinical reports have been published on characteristics of progressive aggravation and late-onset. OBJECTIVES: To identified a new-found pedigree with c.323 G>C mutation leading to progressive aggravation and late-onset loricrin keratoderma. METHODS: Targeted next-generation sequencing of 267 genes associated with all skin abnormalities, sanger sequencing, and bioinformatics tools were used to identify the mutation in this new-found pedigree. Palm skin biopsy was used to observe the clinicopathological features of patient. Further, we constructed pcDNA3.1/V5-His-wild-LORICRIN, pcDNA3.1/V5-His-c.323G>C-LORICRIN, and pcDNA3.1/V5-His-730insG-LORICRIN vectors, nucleofected into HaCaT strain to observe the subcellular localization of loricrin by using the laser scanning confocal microscopy. RESULTS: The proband and his affected father carried a heterozygous c.323 G>C missense mutation (p.Gly108Ala) on LORICRIN. Bioinformatics analysis hinted that it had potential pathogenicity; the types of ligands, enzyme commission active sites, and the spatial structure of protein changed enormously. Laser scanning confocal microscopy showed that the signals from cells transfected with the pcDNA3.1/V5-His-730insG-LORICRIN vector were distributed mainly in the nucleus, whereas those from cells transfected with the pcDNA3.1/V5-His-c.323G>C-LORICRIN vector were mainly located in the cytoplasm. Wild type loricrin was distributed in the nucleus and cytoplasm homogeneously CONCLUSION: The heterozygous c.323G>C missense mutation on LORICRIN caused late-onset and progressive loricrin keratoderma in this large Chinese family. Our study revealed that a large number of loricrin gathered in the cytoplasm may disturb the normal proliferation and terminal differentiation of keratinocytes and lead to the late-onset loricrin keratoderma disease.

miR-617 Promotes the Growth of IL-22-Stimulated Keratinocytes Through Regulating FOXO4 Expression.

Psoriasis is considered as a common chronic and relapsing inflammatory skin disease. MicroRNAs (miRNAs) were found to be related with psoriasis pathogenesis. Nevertheless, the function of miR-617 in psoriasis is still unclear. The miR-617 RNA level was detected using quantitative reverse transcription-PCR (qRT-PCR). Western blot analysis examined the protein level. Cell proliferation was analyzed via cell counting kit-8 (CCK-8) assay. Flow cytometry analysis detected cell cycle and apoptosis. The relationship between miR-617 and forkhead box protein O4 (FOXO4) was confirmed through dual luciferase assay. The miR-617 was up-regulated in psoriatic skin tissues and interleukin-22 (IL-22)-stimulated immortalized human keratinocyte HaCaT cells. Moreover, miR-617 mimics promoted proliferation, cell cycle, and suppressed apoptosis in IL-22-stimulated HaCaT cells. However, miR-617 inhibitor showed opposite effects. Additionally, FOXO4 was a target of miR-617. FOXO4 was down-regulated in psoriatic skin tissues and IL-22-stimulated HaCaT cells. Negative correlation between miR-617 and FOXO4 was identified. FOXO4 overexpression alleviated the effects of miR-617 proliferation, cell cycle and apoptosis in the IL-22-stimulated HaCaT cells. These results demonstrate that miR-617 increases the growth of IL-22-stimulated keratinocytes through targeting FOXO4, which provides a new therapeutic target for psoriasis.

miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT/p70S6K and JNK Pathways through ABHD2.

Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2.

IL22 drives cutaneous melanoma cell proliferation, migration and invasion through activation of miR-181/STAT3/AKT axis.

Cutaneous melanoma (CM) is neoplastic growth of melanocytes with strong potential to proliferate and invade, prone to a fatal disease soon which is beyond surgical clearance. The use of regulator involving in antitumor immune responses has been identified as a potential therapeutic option for CM, but still need fully understood at present. Recently, interleukin 22 (IL22), an immune molecule secreted mostly by CD4+ T cells, was reported having functions in a variety of human diseases including encouragement of lung cancer progression, yet, its role in CM is lacking. Here, we first found elevated expression of IL22 in both serum of CM patients and tissues. Up-regulated IL22 significantly promoted cell proliferation, migration and invasion in CM cells deriving from different original culture history. Moreover, in vivo CM model, IL22 treatment caused a significant increase in tumor size. Additionally, we found these effects accompanied by obvious increased miR-181 expression in CM. Importantly, both in vivo and in vitro results revealed that miR-181 downregulation reversed the effects of IL22 on CM cell proliferation, migration, invasion, and CM tumor size as well. Finally, in CM cells deriving from different culture history, we identified STAT3 to be a target gene of miR-181. Higher expression level of IL22 suppressed STAT3 expression, while enhanced expression of p-AKT, p-ß-catenin and MMP4; however, down-regulation of miR-181 reversed these situations. Thus, we conclude that IL22 promotes CM progression by driving miR-181/STAT3/AKT axis.

Association of brain-derived neurotrophic factor levels and depressive symptoms in young adults with acne vulgaris.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is one of the proteins that contributes to the survival, growth, maintenance of neurons, and plays important roles in the pathophysiology of depression. It has been reported that depression is closely associated with the pathogenesis of acne vulgaris disease. But, there is no report of serum BDNF levels in patients with acne vulgaris. The study aimed to determine the potential association between BDNF and depressive symptoms in young adults with acne vulgaris. METHODS: In this analytical cross-sectional study, the serum BDNF levels were measured in peripheral blood samples of 20 consecutive acne vulgaris patients with depression and 98 consecutive acne vulgaris patients without depression and also compared it with a 59 healthy control group by using a ELISA. The potential correlation between the BDNF levels, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and depressive symptoms such as nine-item patient health questionnaire (PHQ-9) and Athens insomnia scale (AIS) were evaluated with multivariate logistic regression analysis. RESULTS: Our results showed that levels of BDNF expression were lower in consecutive acne vulgaris patients when compared with healthy control (P < 0.05). There was a negative correlation between levels of BDNF and the PHQ-9 scores (r = - 0.486, P < 0.001). Furthermore, acne vulgaris patients with depression showed lower serum BDNF levels (10.96 ± 2.12 ng/ml) compared with acne vulgaris patients without depression (13.85 ± 2.47 ng/ml), as well as with healthy control (14.35 ± 2.70 ng/mg; both P < 0.05). No difference was found in serum BDNF levels between healthy control and acne vulgaris patients without depressive symptoms (z = 0.964, P > 0.05). Similarly, the overall area under the curve of receiver operating characteristic was 0.82, indicating the highly conserving of serum BDNF levels as an biomarker for screening of depression in young adults with acne vulgaris (72% sensitivity and 85% specificity). CONCLUSION: Serum BDNF levels were decreased and negatively associated with depressive symptoms in young Chinese adults with acne vulgaris.

Upregulation of LINC00319 indicates a poor prognosis and promotes cell proliferation and invasion in cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (CSCC), an epidermal keratinocyte-derived skin tumor, is one of the most leading causes of cancer-associated morbidity and mortality worldwide. Long noncoding RNAs have emerged as key regulators of tumor development and progression. Recent studies have identified LINC00319, a long intergenic noncoding RNA, as an oncogene in lung cancer. However, the biological role of LINC00319 in CSCC remains largely unknown. The current study aimed to explore the role of LINC00319 in CSCC and uncover the molecular mechanisms. In current study, we found that LINC00319 was significantly upregulated in both CSCC tissues and cell lines. Besides, the χ2 test showed that increased expression of LINC00319 was associated with larger tumor size, advanced TNM stage, and lymphovascular invasion. Gain-of-function and loss-of-function approaches were applied to investigate the effects of LINC00319 on CSCC cells. Functional studies demonstrated that LINC00319 promoted CSCC cell proliferation, accelerated cell cycle progression, facilitated cell migration and invasion, and inhibited cell apoptosis. Mechanistic studies revealed that LINC00319 exerts its oncogenic functions in CSCC via miR-1207-5p-mediated regulation of cyclin-dependent kinase 3. Taken together, upregulation of LINC00319 implies a potential link with poor prognosis and reflects CSCC progression. Collectively, this study may provide some evidence for LINC00319 as a candidate target in CSCC treatment.

Additional AM Fungi Inoculation Increase Populus cathayana Intersexual Competition.

Sex-specific responses to mycorrhiza have been reported in dioecious plant species, but little attention has been paid to the influence of arbuscular mycorrhizal (AM) fungi on competitive ability under intersexual competition. To further address whether this competition is affected by an additional AM fungi supply, Populus cathayana saplings were chosen and subjected to two mycorrhizal treatments [inoculated and non-inoculated (control) with an additional AM fungi Funneliformis mosseae] while growing with the opposite sex for 3 months. Compared with the control, the additional AM fungi inoculation induced P. cathayana saplings to exhibit significant sexual differences in root structure and nutrient uptake (e.g., cortical layer, cross-section area, radius of root tips, and N, K, and Mg content), and enlarged sexual differences in morphology and biomass accumulation (e.g., leaf number increment, shoot height increment, total leaf area, total specific root length, stem dry mass, leaf dry mass, and total dry mass). Meanwhile, inoculated females presented higher values in most of these traits mentioned above than males under intersexual competition. Therefore, we conclude that the intersexual competition can be increased by an additional AM fungi supply, with females gaining more symbiosis-mediated benefits than males.

Root-mediated sex recognition in a dioecious tree.

Recent studies have demonstrated that plants can determine the identity of neighbouring roots (e.g., self and non-self, kin and non-kin), but whether they can discriminate by sex remains an open question. Here, we predict that dioecious plants can modulate their root performance in response to local root conditions related to sex. Female and male Populus cathayana cuttings were planted in a greenhouse in root-owner (one individual without a root neighbour) or root-sharer pairs (two individuals with roots neighbouring each other) with equal amounts of nutrients and space per plant in three combinations (females-females, males-males or females-males); root morphology, biomass and allocation were investigated. P. cathayana root-sharers altered their root growth in same-sex but not in different-sex combinations. Females enhanced root growth and allocation but decreased root proliferation (greater diameter with reduced branching and specific root length) in the presence of a female root neighbour, while males reduced root growth but increased root morphological proliferation in contact with another male. Therefore, the effect of a neighbour of the same sex differed from that of a neighbour of the opposite sex, which suggests that these plants can recognize the sexual identity of their neighbours.

[Study on propagation technology of Acanthopanax trifoliatus by cuttings].

OBJECTIVE: In order to obtain substantial clonal plants, we studied the cuttings propagation technology. METHODS: The cutting roots and stems of Acanthopanax trifoliatus were used as plant materials, and different materias, seasons and other conditions for cutting propagation were tested. RESULTS: It showed that the survival rate of stem segments was higher than that of root segments. The test of age of plant materials found that high survival rate could be obtained from semi-lignified stem segments and the segments from the base stem could survive successfully. Autumn was more suitable for plants' survival. Moreover, the rooting rate reached 89.4% by inserting segments with leaves into sand soil after dipping into 1500 mg/L IBA for 10 s, and with plastic membrane and shading net covered. CONCLUSION: The rooting rate can increase significantly by collecting semi-lignified basal stems in autumn, cutting them for leaf cuttings, and inserting them into sand soil after dipping into 1500 mg/L IBA for 10 s.