BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Skin modeling of transdermal drug delivery system refers to experimental models that mimic the structure and function of human skin to explore and evaluate absorption,penetration,and efficacy of medicines in transdermal drug delivery.It provides an alternative to traditional human skin experiments and reduces the use of human skin in medical research,which is convenient,controllable,and cost effective.For skin models of transdermal drug delivery systems,this article introduces commonly used animal skin models,artificial skin models,and recombinant human skin models from the perspective of the transdermal absorption pathway of medicines,and analyzes their advantages,disadvantages,and applications so provide references the research and development of transdermal formulations and topical therapies.

OBJECTIVE To investigate the expression and clinical significance of tissue inhibitor of matrix metalloproteinase-3(TIMP-3)and fibronectin 1(FN1)in nasopharyngeal carcinoma patients.METHODS A total of 102 nasopharyngeal cancer patients admitted to Taihe Hospital from May 2018 to May 2019 were selected as the observation subjects(case group),and another 102 patients with chronic nasopharyngitis were selected as the control group.Immunohistochemistry was applied to determine the expression of TIMP-3 and FN1 in both groups.The prognosis of the patient is followed up.Kaplan-Meier method was applied to analyze the relationship between the expression levels of TIMP-3 and FN1 in nasopharyngeal carcinoma tissue with the 3-year prognostic survival of patients.The influencing factors were analyzed using Cox risk regression method.RESULTS The positive rate of TIMP-3 protein in the case group(25.49%,26/102)was lower than that in the control group(82.35%,84/102),with a statistically significant difference(χ2=66.369,P<0.05);the positive rate of FN1 protein(71.57%,73/102)was higher than that in the control group(20.59%,21/102),with a statistically significant difference(χ2=53.348,P<0.05).The expression of TIMP-3 and FN1 was related to lymph node metastasis and TNM staging(P<0.05).During the 5-year follow-up period,64 of 102 nasopharyngeal cancer patients with disease-free survival were categorized into the survival group,and 38 nasopharyngeal cancer patients who experienced death were categorized into the death group.The 5-year survival rate(56.58%,43/76)of patients with TIMP-3 negative expression in nasopharyngeal carcinoma tissue was lower than that of patients with TIMP-3 positive expression(80.77%,21/26)(χ2=8.921,P<0.05).The 5-year survival rate(23/29,79.31%)of patients with FN1 negative expression in nasopharyngeal carcinoma tissue was higher than that of patients with FN1 positive expression(41/73,56.16%)(χ2=8.596,P<0.05).FN1 positive,TNM staging,and lymph node metastasis were independent risk factors for mortality in nasopharyngeal carcinoma patients,while TIMP-3 was a protective factor for mortality in nasopharyngeal carcinoma patients(P<0.05).CONCLUSION TIMP-3 expression decreases and FN1 expression increases in tissues of nasopharyngeal carcinoma patients.Both are closely related to the progression and prognosis of nasopharyngeal carcinoma,and may serve as potential prognostic markers for nasopharyngeal carcinoma.

OBJECTIVE To prepare spider fibroin membrane loaded with Periplaneta americana extract， and investigate its characterization， in vitro drug release property and cytotoxicity. METHODS Using natural spider silk collected from Chilobrachys guangxiensis as raw material， P. americana extract as model drug， the drug-loaded spider fibroin membrane （hereinafter referred to as drug-loaded membrane） was prepared by solvent casting method. The material matrix spider fibroin membrane without P. americana extract （hereinafter referred to as blank membrane） was prepared with same method. The membrane structure was characterized by static water contact angle， Fourier infrared chromatography， X-ray diffraction and scanning electron microscopy from different angles； drug release characteristics in artificial saliva were simulated in vitro to evaluate the drug sustained-release performance. MTT assay was adopted to validate the cytotoxicity of drug-loaded membrane. RESULTS The drug-loaded membrane was prepared， and the static water contact angle was less than 90°， which was less than that of blank membrane. The drug-loaded membrane showed the characteristic absorption peak to polypeptide of P. americana extract at 1 500-1 700 cm－1. X-ray diffraction and scanning electron microscopy also proved that the drug was successfully loaded into the pellicle. The release time of the pellicle in artificial saliva was more than 200 min. The MTT test results showed that the cell proliferation rates of blank membrane and drug-loaded membrane were 84.6% and 79.4% （both greater than 70%）， respectively， without significant potential cytotoxicity. CONCLUSIONS Drug-loaded membrane prepared with natural spider silk has a certain sustained-release effect in artificial saliva， which can be further developed as a drug sustained-release carrier with excellent biological characteristics and biocompatibility.

Objective:To investigate the expression of human epidermal growth factor receptor 2(HER2)and P53 and their relationship with microsatellite instability(MSI)in gastric cancer tissues.Methods:A total of 103 patients diagnosed with gastric cancer between January 2018 and October 2020 at Yueyang Hospital were enrolled in this study.HER2, P53 and mismatch repair proteins in gastric cancer tissues were detected with immunohistochemical(IHC)methods, and MSI screening was conducted at 7 sites with a new Idylla MSI(multiple fluorescent PCR)method.Results:Of 103 gastric cancer patients in this study, 77(74.8%)showed microsatellite stability(MSS)and 26(25.2%)showed MIS via IHC, and PCR also detected 77 MSS cases and 26 MSI cases.In MSI, there was more low HER2 expression than high HER2 expression, and the rate of low HER2 expression in MSI was higher than the rate of high HER2 expression in MSI( P<0.05).Also in MSI, there was more low P53 expression than high P53 expression, and the rate of low P53 expression in MSI was higher than the rate of high expression in MSI( P<0.05). Conclusions:MSS may exist in the process of gastric carcinogenesis and in gastric cancer it may be accompanied by low expression of HER2 and p53 in cancer tissues.There may be a mutually exclusive relationship between MSI and expressions of HER2 and p53, suggesting that carcinogenic mechanisms involving MSI may be very different from those involving HER2 and p53.MSI detection is very valuable in guiding treatment drug selection and prognosis assessment.

Background:Serum pepsinogens (PGs),as a serologic marker for gastric mucosal lesions,can reflect the functional status of gastric mucosa. Helicobacter pylori (Hp)infection can cause pathological changes in gastric mucosa,and has been reported to influence the serum level of PGs. Aims:To explore the influence of Hp infection on diagnostic performance of serum PGs for gastric mucosal lesions. Methods:The endoscopic findings,biopsy pathology (including Giemsa staining) and serum PGs test in 1216 cases of patients from July 2014 to June 2015 at the First Affiliated Hospital of Jiaxing University were collected. Patients were categorized according to the pathological diagnosis and Hp status,and the results of serum PGs test were analyzed between different groups. Results:When patients were classified by gastric mucosal lesion,no significant differences were found in serum levels of PGⅠ,PGⅡ,ratio for PGⅠ/ Ⅱ (PGR)and proportion of PG-positive (PGⅠ≤70 μg/ L and PGR < 3. 0)patients of different mucosal lesion groups with Hp-positive status (P >0. 05),whereas significant differences were observed in serum levels of PGⅠ,PGⅡ,PGR and proportions of patients with PGⅠ≤70 μg/ L or PGR < 3. 0 of different mucosal lesion groups with Hp-negative status (P < 0. 05). When patients were classified by Hp status,PGⅠ level and PGR were lower and PGⅡ level and proportion of PG-positive patients were higher in Hp-positive patients than in Hp-negative patients in any of the gastric mucosal lesion groups (P < 0. 05 in part of the comparisons). Conclusions:Hp infection is strongly associated with the alterations in serum PGs test,which narrows the differences in PGs between groups with different gastric mucosal lesions and expands that within the same mucosal lesion, subsequently decreasing PGR and increasing the proportion of PG-positive patients. Patients negative for Hp infection may need new cut-off value of serum PGs test to improve the sensitivity for diagnosis of gastric mucosal lesion.

This study aimed at exploring a fast method to accurately identify the medicinal insect Vespa mandarinia Smith from its adulterants using DNA barcode and COI sequences.The extracted DNAs from V.mandarinia and its adulterants V.soror were amplified by polymerase chain reaction (PCR) and sequenced bilaterally based on COI barcode sequence investigation.The information of the COI sequences of V.mandarinia and V.soror were gathered from GenBank.All the sequences were compared and analyzed,and their intraspecific and interspecific genetic distances were calculated using MEGA 6.06.In addition,the phylogenetic tree was established with neighbor-joining (NJ) method.As a result,the COI sequences of V.mandarinia and V.soror were successfully amplified.The minimum interspecific distance between V.mandarinia and its adulterants was 0.152 ± 0.017,being considerably larger than the maximal intraspecific distance between V.mandarinia,0.009±0.004.The constructed phylogenetic tree showed an independent branch for each species.It was concluded that the DNA barcode based on COI sequence can efficiently identify V.mandarinia and its adulterants.This study provided an innovative tool for the quality control and market regulation of Chinese materia medica,securing the safe medication of V.mandarinia.

OBJECTIVE: To systematically review the efficacy and safety of taxane, cisplatin, and fluorouracil (Tax-PF) as induction chemotherapy for advanced head and neck cancer. METHOD: Literature about the efficacy and safety of Taxane-cisplatin-fluorouracil as induction chemotherapy for advanced head and neck cancer was retrieved from digital databases of PubMed, Embase, SpringerLink, MEDLINE and the Cochrane Library before February 2015. Data extraction and quality assessment of included studies were conducted by two reviewers independently. Stata 13.0 was then used to perform Meta-analysis. RESULT: A total 7 randomized controlled trials involving 2,702 were included. The 3-year OS rate [HR = 1.14, 95% CI (1.03, 1.25), P < 0.01], 3-year PFS rate [HR = 1.24, 95% CI (1.08, 1.43), P < 0.01], 5-year OS rate [HR = 1.30, 95% CI (1.09, 1. 55), P < 0. 01], 5-year PFS rate [HR = 1.39, 95% CI (1.14, 1.70), P < 0.01] and ORR to chemotherapy [OR = 1.66, 95% CI (1.35, 2.05), P < 0.01] of the patients in the Tax-PF group were statistically superior to those in the PF group. In terms of toxicities, the incidence of febrile neutropenia [OR = 2.36, 95% CI (1.62, 3.46), P < 0.01], alopecia [OR = 8.22, 95% CI (3.99, 16.92), P < 0.01], diarrhea [OR = 1.57, 95% CI (1.05, 2.36), P< 0.05] and leucopenia [OR = 2.79, 95% CI (1.86, 4.21), P < 0.01] was higher in the Tax-PF group than that in the PF group. CONCLUSION The Tax-PF induction chemotherapy improved PFS and OS, and the ORR was better as compared to PF-based therapy regimens at the cost of a higher incidence of adverse events.
Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Cisplatin ; therapeutic use ; Fluorouracil ; therapeutic use ; Head and Neck Neoplasms ; drug therapy ; Humans ; Induction Chemotherapy ; Randomized Controlled Trials as Topic ; Taxoids ; therapeutic use

OBJECTIVE: To analyze and explore the association between the 1607(1G/2G) single nucleotide polymorphism (SNP) in promoter of matrix metalloproteinase-1 (MMP-1) gene and susceptibility of head and neck cancer (HNC) by Meta-analysis. METHOD: By the end of January 2014, the published literatures were collected for the case-control studies evaluating the relationship between HNC and -1607 SNP of MMP-1 gene from English and Chinese literature databases according to the inclusion and exclusion criteria. Then the meta-analysis, the heterogeneity, bias and sensitivity of the results of the eligible literatures were conducted by Stata 10. 0. RESULT: A total of 9 studies including 2049 patients with HNC and 2158 controls were extracted for systematic review on the association of MMP-1 (-1607) 1G/2G SNP with the risk of HNC. Meta-analysis which based on random effects model showed that MMP-1 (-1607) 1G/2G SNP can significantly increase the risk of HNC[1G2G + 2G2G vs. 1G1G: OR = 1.45, 95% CI 1.25-1.68, P < 0.01; 2G2G vs. 1G1G + 1G2G:OR = 1.77, 95% CI 1.37-2.30, P < 0.01; 2G vs. 1G: OR = 1.52, 95% CI 1.26-1.85, P < 0.01; 2G2G vs. 1G1G: OR = 2.06, 95% CI 1.41-3.01, P < 0.01). CONCLUSION MMP-1 (-1607) 1G/2G SNP has close relationship with HNC susceptibility, people who with 2G2G genotype carriers are susceptible to HNC.
Asia ; Asian Continental Ancestry Group ; Case-Control Studies ; Genotype ; Head and Neck Neoplasms ; enzymology ; ethnology ; genetics ; Humans ; Matrix Metalloproteinase 1 ; genetics ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic