MiRNAs can function as oncogenes or tumor suppressor genes. The abnormal expression of miRNAs leads to tumor malignant phenotypes, such as cell proliferation, apoptosis, invasion and metastasis, through which it is involved in the process of tumor initiation, progression and transcriptional regulation network. Therefore, it is important to clarify the mechanism of miRNA involved in the process of tumor initiation and progression. MiRNA regulation mechanism in tumor initiation and progression includes one-to-many and many-to-one regulation between TF-to-miRNA and miRNA-to-target gene, which increases the complexity of miRNA regulation, thus affecting the biological behavior of the tumor, The expression and activity of Drosha and Dicer in the process of miRNA affect the synthesis of mature miRNA and involve in the process of tumor initiation and progression;ceRNA may bind with miRNA by competing with miRNA targeting genes and affect biological function of miRNA as miRNA inhibitor. Therefore the abnormal expression and structure of ceRNA is an important molecular mechanism of tumor initiation and progression. This complicated regulation network comprised by multi-dimensional regulation model and specific regulation of tumor initiation and progression provides impetus to exploring the functional restoration of miRNA as a novel target for cancer diagnosis and therapy.

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose

Objective To compare the dosimetry difference among three-dimensional conformal radiotherapy (3 DCRT),simplified intensity-modulated radiotherapy (sIMRT) and intensity-modulated radiotherapy (IMRT) in whole pelvic irradiation in postoperative rectal carcinoma,in order to optimize the protocol for clinical practice.Methods From 2006 to 2008,10 patients with stage II and ID rectal cancer after radical resection (Dixon surgery) participated in this study.3DCRT,sIMRT and IMRT were performed for each patient.The dose distribution of target volume and normal tissues,conformal index (CI) and HI were analyzed using the dose-volume histogram (DVH).Results The CI for PTV of IMRT and sIMRT was superior to that of 3DCRT.3DCRT had the best HI in PTV target area dose distribution,while IMRT was similar with sIMRT,however,there were no significant difference among them.As regarded as the protection on organs at risk,for bladder,IMRT was superior to 3DCRT and slightly better than sIMRT;for small intestine,sIMRT showed better performance than 3DCRT while IMRT was better than sIMRT but with no significant difference;for colon,no dosimetry difference was found among three plans;for caput femoris,IMRT and sIMRT were better than 3DCRT.Additionally,sIMRT was similar to 3DCRT in MU of segments,but significantly lower than IMRT.The mean values of total MU for 3DCRT,sIMRT and IMRT were 569.73 ±48.69,542.97 ±69.78,and 770.25 ±73.12,respectively.Conclusions All of 3DCRT,sIMRT and IMRT could provide target area with sufficient and accurate dose,meanwhile they could also protect organs at risk well on rectal cancer after radical resection.Compared with 3DCRT plan and IMRT plan,sIMRT plan might be the optimal plan for clinical practice.

To investigate theological properties of common hydrophilic gel excipients such as Carbopol based on viscosity, the viscosity was determined by rotation method and falling-ball method. Linear regression was made between ln(eta) and concentration, the slope of which was used to explore the relation between viscosity and concentration of different excipients. The viscosity flow active energy (E(eta)) was calculated according to Arrhenius equation and was used to investigate the relation between viscosity and temperature of different excipients. The results showed that viscosities measured by two methods were consistent. Concentration of guargum (GG) and hydroxypropylmethyl cellulose (HPMC) solution had a great influence on the viscosity, k > 5; while concentration of polyvinylpyrrolidone-K30 (PVP-K30) and polyethylene glycol 6000 (PEG6000) exerted a less effect on viscosity, k < 0.2; viscosity flow active energy of different excipients were close, which ranged from 30 to 40 kJ x mol(-1). Therefore, theological properties study could provide the basis for application of excipients and establish a foundation for the research of relation between excipients structure, property and function.

Alcoholic liver disease is liver disease caused by heavy and/or chronic alcohol consumption.Bile acids are synthesized in the liver and regulate the body through liver-intestinal circulation.Many studies have shown that bile acid is closely related to alcoholic liver disease.Alcohol intake can cause liver damage by affecting bile acid synthesis,hepato-enteric circulation and intestinal flora.This article summarizes the mechanism of action of bile acids in alcoholic liver disease and the current research status of improving alcoholic liver disease based on bile acid regulation,in order to provide new ideas for future research on the prevention and treatment of alcoholic liver disease.

Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.

OBJECTIVE: To localize and define the region of nucleus export signal (NES) on BRD7, and determine the role of this region in nucleus export of the external protein. METHODS: Based on an in vitro expressed model of green fluorescence protein (GFP), we performed DNA walking analysis to set BRD7 into several sections according to the structural characteristics of BRD7, investigated the effect of different sections of BRD7 on nucleus export of GFP, defined the region of nucleus export signal sequence of BRD7, and further ascertained the content of amino acids in BRD7 and potential localization of BRD7 NES by bioinformatics. RESULTS: B7C1 fragments ranged from aa219 to aa450 in BRD7 were found to target the external protein GFP into the cytoplasm detected by GFP direct fluorescence, which could be inhibited by NES inhibitor Leptomycin B (LMB). This region was rich in hydrophobic amino acid residues but no typical NES with characteristics of leucine-rich sequence by bioinformatics. CONCLUSION The region from aa219 to aa450 is primarily defined as an atypical NES in BRD7.
Animals ; Base Sequence ; COS Cells ; Cell Nucleus ; metabolism ; Chlorocebus aethiops ; Chromosomal Proteins, Non-Histone ; genetics ; metabolism ; Cytoplasm ; metabolism ; Escherichia coli ; genetics ; metabolism ; Green Fluorescent Proteins ; genetics ; Humans ; Molecular Sequence Data ; Nuclear Export Signals ; Recombinant Proteins ; genetics ; metabolism

Background:The musk glands of adult male Chinese forest musk deer(Moschus berezovskii Flerov,1929)(FMD),which are considered as special skin glands,secrete a mixture of sebum,lipids,and proteins into the musk pod.Together,these components form musk,which plays an important role in attracting females during the breeding season.However,the relationship between the musk glands and skin of Chinese FMD remains undiscovered.Here,the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing(RNA-seq),and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin.Methods:A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted.Then,based on the anatomical structure of the musk gland,skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD.These tissues were used for RNA-seq,hematoxylin-eosin(HE)staining,immunohistochemistry(IHC),western blot(WB),and quantitative real-time polymerase chain reaction(qRT-PCR)experiments.Results:Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod,while juvenile FMD did not have any well-developed musk pods.Transcriptomic data revealed that 88.24%of genes were co-expressed in the skin and musk gland tissues.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis found that the genes co-expressed in the abdomen skin,back skin,and musk gland were enriched in biological development,endocrine system,lipid metabolism,and other pathways.Gene Ontology(GO)enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division.Moreover,the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific.qRT-PCR and WB revealed that sex-determining region Y-box protein 9(Sox9),Caveolin-1(Cav-1),and androgen receptor(AR)were expressed in all three tissues,although the expression levels differed among the tissues.According to the IHC results,Sox9 and AR were expressed in the nuclei of sebaceous gland,hair follicle,and musk gland cells,whereas Cav-1 was expressed in the cell membrane.Conclusions:The musk gland of Chinese FMD may be a derivative of skin tissue,and Sox9,Cav-1,and AR may play significant roles in musk gland development.

PURPOSE: The long non-coding RNA H19, a conservatively imprinted gene, acts as a molecular sponge for the let-7 family, which has been identified as a set of tumor suppressors. However, the combined prognostic value of H19 and let-7a signature in breast cancer patients remains unclear. METHODS: In this research we assessed the prognostic value of the combined H19 and let-7a signature in breast cancer patients by retrospectively reviewing that data of 79 patients who underwent neoadjuvant chemotherapy; we also investigated the expression and function of H19 in breast cancer cell lines in vitro. Survival data were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression method. As determined using X-tile, the optimal cutoff value for the risk score to assess progression-free survival (PFS) based on the combined signature was –0.1. RESULTS: Patients with an overall positive treatment response had higher let-7a and lower H19 levels. In addition, let-7a expression was negatively correlated with H19 expression. Patients with a risk score of >–0.1 had shorter overall survival and PFS. In vitro data showed that chemoresistant cell lines exhibit higher H19 and lower let-7a levels and knockdown H19 restores paclitaxel sensitivity. CONCLUSION: Our results suggest that the combined let-7a and H19 signature is a novel prognostic factor for breast cancer patients treated with neoadjuvant chemotherapy.
Breast Neoplasms* ; Breast* ; Cell Line ; Disease-Free Survival* ; Drug Therapy ; Humans ; In Vitro Techniques ; Methods ; Neoadjuvant Therapy ; Paclitaxel ; Porifera ; Prognosis ; Retrospective Studies ; RNA, Long Noncoding

Objective To observe the alterations in functional complexity of brain regions in autism spectrum disorder(ASD)patients and correlations with the predicted brain age.Methods Open brain resting-state functional MRI(rs-MRI)data of 93 ASD patients and 96 typically developing adolescents(healthy subjects)were downloaded.The functional complexity in brain regions were extracted with self-developed virtual digital brain software,and the alterations in functional complexity of brain regions in ASD patients and correlations with their ages were analyzed.Two networks were prospectively trained with data of 65 ASD patients and 67 healthy subjects as the training set to predict brain age,and the results were evaluated,and the predicting errors were compared using test set,i.e.the other 28 ASD patients and 29 healthy subjects.Results Compared to healthy subjects,on the basis of anatomical automatic labeling(AAL)atlas,ASD patients exhibited significantly reduced functional complexity based on Shannon entropy in the left precuneus,left cuneus and right parahippocampal gyrus.Conversely,functional complexity of ASD patients based on permutation entropy significantly increased in the left cuneus and right cerebellar Crus Ⅱ region.The left hippocampus showed reduced functional complexity based on Pearson correlation coefficient,while the left middle temporal gyrus showed increased functional complexity based on Pearson correlation coefficient.The functional complexity in brain regions of ASD patients were not closely correlated with ages(all|r|＜0.4).According to the trained fully connected network,the predicted brain ages of ASD patients and healthy subjects in test set were all lower than their physiological ages,but no significant difference was found between the prediction errors of ASD patients and healthy subjects(P=0.283).Conclusion Functional complexity changed in some brain region functions in ASD patients.The predicted brain ages of ASD patients based on the obtained fully connected network were on the low side,but not obviously affected by the alterations of functional complexity in brain regions.