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Objective: The aim of this study was to investigate the role and mechanisms of miR-155 in chronic spontaneous urticaria (CSU). Methods: The expression level of miR-155 in the skin tissues of patients with CSU and experimental rats were detected by RT-qPCR, followed by the measurement of the histamine release rate in the serum through the histamine release test. Besides, hematoxylin & eosin staining was used to observe the pathological changes of the skin tissues; Corresponding detection kits and flow cytometry to measure the changes of immunoglobulins, inflammatory cytokines and T cell subsets in the serum of rats in each group; and western blot to check the expression level of proteins related to JAK/STAT signaling pathway in the skin tissues. Results: Knockdown of miR-155 reduced the number and duration of pruritus, alleviated the skin damage, and decreased the number of eosinophils in CSU rats. Moreover, knockdown of miR-155 elevated the serum levels of IgG and IgM, decreased the levels of IgA and inflammatory cytokines, and reduced the proportion of CD4 + and CD4 + CD25 + T cells, as well as the CD4+/CD8 + ratio in CSU rats. However, Tyr705 intervention could reverse the effects of knockdown of miR-155 on CSU model rats. Furthermore, we found that knockdown of miR-155 significantly reduced the protein expression of IRF-9, as well as the P-JAK2/JAK2 and P-STAT3/STAT3 ratios in the skin tissues of CSU rats. Conclusion: Knockdown of miR-155 can alleviate skin damage and inflammatory responses and relieve autoimmunity in CSU rats by inhibiting the JAK/STAT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Psoriasis is a kind of immune-mediated, chronic, inflammatory skin disease, which is often associated with different degrees of psychological disorders. Specifically, there is a significant correlation between psoriasis and depression, and they show the relationships of reciprocal causation and mutual promotion. Psoriasis with depression is more harmful than simple psoriasis, and its prognosis is worse, which brings a huge burden to the family and society and is worthy of clinical attention. Based on the pathogenic factors of western medicine and pathogenesis of traditional Chinese medicine in psoriasis with depression, the paper summarized and elaborated the research progress on the mechanism of traditional Chinese medicine in the treatment of psoriasis with depression, in order to provide new ideas for clinical treatment. [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical efficacy, immune inflammatory factors and hemorheology of patients with plaque psoriasis by using fire acupuncture combined with the theory of midnightnoon ebb-flow. Methods: Sixty-two patients with plaque psoriasis who met the diagnosis and inclusion criteria were randomly divided into control group and fire acupuncture with midnightnoon ebb-flow, with 31 cases in each group. The control group was treated with carpotriol ointment for external use, while the fire acupuncture group was treated with fire acupuncture with midnightnoon ebb-flow on the basis of the former and selected points by the opening method through midnight-noon ebb-flow theory. The patients in both groups were treated for 8 weeks and followed up for 4 weeks. The levels of PASI, DLQI, PSQI, HAMA, hs-CRP, TNF-α and hemorheology indexes in 2 groups before and after treatment were observed, including the comparison of whole blood viscosity, plasma viscosity and hematocrit. Results: PASI, DLQI, PSQI, HAMA, hs-CRP, TNF-α, blood viscosity and hematocrit levels were significantly improved after treatment (P < 0. 05, P < 0. 01), and the group in fire acupuncture with midnight-noon ebb-flow was significantly better than control group after treatment (P<0.01). Conclusion: fire acupuncture with midnight-noon ebb-flow can improve the sleep quality of patients with psoriasis, relieve anxiety and effectively improve the blood cell rheology and microcirculation, alleviate clinical symptoms and improve the quality of life. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the three most common gynecological malignant tumors worldwide. The prognosis of patients suffering from this malignancy remains poor because of limited therapeutic strategies. Herein, we investigated the role of a long noncoding RNA named MIR4697 host gene (MIR4697HG) in the cell growth and metastasis of ovarian cancer. Results showed that the transcriptional level of MIR4697HG in cancerous tissues increased twofold compared with that in adjacent noncancerous tissues. MIR4697HG was differentially expressed in ovarian cancer cell lines, with the highest levels in OVCAR3 and SKOV3 cells. MIR4697HG knockdown by specific shRNA significantly inhibited cell proliferation and colony formation in both OVCAR3 and SKOC3 cells. Consistently, in a xenograft model of ovarian cancer, MIR4697HG depletion also significantly restricted tumor volumes and weights. Furthermore, MIR4697HG knockdown inhibited cell migration and invasion capacities. Invasion ability was inhibited by 58% in SKOV3 cells and 40% in OVCAR3 cells, and migration ability was inhibited by 73% in SKOV3 cells and 62% in OVCAR3 cells after MIR4697HG knockdown. MIR4697HG knockdown also caused a decrease in matrix metalloprotease-9, phosphorylated ERK, and phosphorylated AKT. These data suggested that MIR4697HG promoted ovarian cancer growth and metastasis. The aggressive role of MIR4697HG in ovarian cancer may be related to the ERK and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

Aberrant activation of the hedgehog (Hh) signaling pathway has been implicated in the epithelial-to-mesenchymal transition (EMT) and cancer stem-like cell (CSC) maintenance; both processes can result in tumor progression and treatment resistance in several types of human cancer. Hh cooperates with the epidermal growth factor receptor (EGFR) signaling pathway in embryogenesis. We found that the Hh signaling pathway was silenced in EGFR-TKI-sensitive non-small-cell lung cancer (NSCLC) cells, while it was inappropriately activated in EGFR-TKI-resistant NSCLC cells, accompanied by EMT induction and ABCG2 overexpression. Upregulation of Hh signaling through extrinsic SHH exposure downregulated E-cadherin expression and elevated Snail and ABCG2 expression, resulting in gefitinib tolerance (P < 0.001) in EGFR-TKI-sensitive cells. Blockade of the Hh signaling pathway using the SMO antagonist SANT-1 restored E-cadherin expression and downregulate Snail and ABCG2 in EGFR-TKI-resistant cells. A combination of SANT-1 and gefitinib markedly inhibited tumorigenesis and proliferation in EGFR-TKI-resistant cells (P < 0.001). These findings indicate that hyperactivity of Hh signaling resulted in EGFR-TKI resistance, by EMT introduction and ABCG2 upregulation, and blockade of Hh signaling synergistically increased sensitivity to EGFR-TKIs in primary and secondary resistant NSCLC cells. E-cadherin expression may be a potential biomarker of the suitability of the combined application of an Hh inhibitor and EGFR-TKIs in EGFR-TKI-resistant NSCLCs. [ABSTRACT FROM AUTHOR]

The study objectives were to investigate the relationship between early exposure to genistein and obesity in young adulthood and to evaluate changes in reproductive health during puberty and adulthood following in utero exposure to genistein. Thirty-two female rats were randomized into four groups; low dose 400 mg genistein/kg diet group (LG), mid-dose 1200 mg genistein/kg diet group (MG), high dose 3600 mg genistein/kg diet group (HG), and control group without genistein diet (CON). Rats were fed genistein at the beginning of pregnancy along with a high-fat diet. Pups were sacrificed at week 4 and week 8 after birth. High performance liquid chromatography (HPLC) results showed a correlation between maternal genistein intake and genistein concentration in pups' plasma. Compared to CON, body weight reduced significantly in male HG group at week 8. No statistical differences were found in plasma estradiol (E2), testosterone (T), interleukin (IL)-6, and C-reactive protein (CRP) levels with early genistein exposure. Furthermore, uterine histopathology showed notable changes in groups HG and MG compared with CON at week 4 and week 8. In conclusion, maternal genistein supplement could reduce body weight in male pups and alter uterine histopathology in female pups. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a common chronic inflammatory skin disease with high recurrence rates and increasing incidence. Patients require long-term medication to reduce symptoms and prevent disease progression. Therefore, the development of treatments with high efficiency and low rate of adverse events is of utmost importance. Traditional Chinese medicine (TCM) plays an outstanding role in reducing disease symptoms and improving quality of life. The aim of this trial is to clarify the treatment efficacy, safety, and control of disease recurrence in patients with psoriasis with blood-stasis syndrome treated with Taodan granules (TDKL)., Methods: This trial is a five-center, randomized, double-blind, placebo-controlled study planned to transpire between September 1, 2019, and December 31, 2021. A sample size of 216 participants (108 per group) with mild-to-moderate psoriasis will be randomly assigned to receive TDKL or placebo twice per day, 7 days per week, for 8 weeks. The study duration will be 17 weeks, including a 1-week screening period, 8 weeks of intervention, and another 8 weeks of follow-up. The primary outcomes are improvement in the Psoriasis Area and Severity Index score and recurrence rate after 8 weeks of treatment. Secondary outcomes include body surface area affected and the scores for the Physician Global Assessment, Dermatology Life Quality Index, pain-related quality of life, pain on the visual analogue scale, and TCM syndromes. The number, nature, and severity of adverse events will be carefully recorded., Discussion: The study results will help clarify the safety and efficacy of TDKL as treatment for psoriasis with respect to both disease regression and recurrence rate. We expect that this study will provide high-quality evidence with important public health implications that may alter the approach to psoriasis management in China., Trial Registration: The trial has been registered at ClinicalTrials.gov (ID: NCT03942198)., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Annals of Translational Medicine. All rights reserved.)

Purpose: Ovarian cancer is one of the leading causes of death for women worldwide. The present study aims to investigate the role of G protein-coupled receptor 137 (GPR137) in the biological activities of ovarian cancer cells., Methods: (QUERY: Please supply Methods for Abstract), Results: G protein-coupled receptor 137 was highly expressed in clinical ovarian cancer tissues and exhibited the highest protein levels in SKOV3 cells and OVCAR3 cells. Knockdown of GPR137 caused significant decreases in cell proliferative rates and colony formation abilities in SKOV3 cells and OVCAR3 cells and also inhibited the in vivo tumorigenesis in a xenograft model. It was observed that knockdown of GPR137 inhibited cell motility by up to 40% in SKOV3 cells and approximately 65% in OVCAR3 cells in wound-healing assay. Cell migration abilities were consistently inhibited by 68.2% in SKOV3 cells and 59.3% in OVCAR3 cells, whereas cell invasion abilities were inhibited by 64.0% and 74.2% in SKOV3 and OVCAR3 cells, respectively, after knockdown of GPR137. When GPR137 was depleted, epithelial markers were increased, while mesenchymal markers decreased., Conclusions: Our data suggest that GPR137 plays pro-oncogenic roles in ovarian cancer via regulation of the PI3K/AKT pathway. These observations might pave new insights into therapeutic strategies against human ovarian cancer.

Objective: To investigate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) content and activity in lung adenocarcinoma cell lines and its correlation with radiosensitivity., Methods: The content and activity of DNA-PKcs were analyzed in two lung adenocarcinoma cell lines A549 and H1299 by Western blotting and the Signa TECT DNA-PK assay kit. The dose-survival relationship for two cell lines was analyzed using clonogenic formation assay., Results: A549 was more radiosensitive than H1299. The survival fractions at 2 Gy (SF2) were 0.7412 in A549 cell line and 0.2473 in H1299 cell line. The content of DNA-PKcs was significantly higher in A549 cells than in H1299 cells (t=10.37, P<0.001). The integrated optical densities were 3.29-/+0.44 in A549 cells and 0.50-/+0.17 in H1299 cells. DNA-PKcs activities in A549 and H1299 cells were 8.29-/+1.37 and 2.47-/+1.09, respectively, showing a significant difference between them (t=5.76, P=0.005)., Conclusion: DNA-PKcs is an important factor to affect the radiosensitivity of lung adenocarcinoma cell lines.

Objective: To explore the association between XAGE-1b gene expression and the clinical characteristics of non-small cell lung cancer (NSCLC)., Methods: Tumor tissue and adjacent normal lung tissue specimens were obtained surgically from 30 patients with resectable NSCLC, from which the total RNA was extracted for RT-PCR to amplify full-length XAGE-1b gene. The products of RT-PCR were identified by electrophoresis and sequencing. The expression of XAGE-1b gene and its association with the clinical characteristics of the patients were analyzed., Results: In the 30 tumor tissue specimens, the expression rate of XAGE-1b gene was 40%, but none of the normal lung tissues expressed this gene. The gene expression was not related to the patients' age, gender, tumor differentiation or clinical stages, but showed significant correlation to their pathological classification. The expression rate of XAGE-1b gene in adenocarcinoma was much higher than that in tumors of other pathological types (61.1% vs 8.3%, P=0.015). XAGE-1b gene expression tended to increase with the TNM stages, which, however, failed to find statistical data support (P>0.05)., Conclusions: XAGE-1b gene is highly expressed in lung adenocarcinoma, and can be an ideal target for tumor immunotherapy.