Microarray gene expression analysis of chemosensitivity for docetaxel,cisplatin and 5-fluorouracil(TPF)combined chemotherapeutic regimen in hypopharyngeal squamous cell carcinoma

Objective: To screen out a set of candidate genes which could help to determine whether patients with hypopharyngeal squamous cell carcinoma (HSCC) could benefit from docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy. Methods: Gene-expression profiles in 12 TPF-sensitive patients were compared to 9 resistant controls by microarray analysis. Subsequently, expression levels of potential biomarkers in chemosensitive cell line FaDu after TPF treatment were observed by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Through microarray analysis, 1,579 differentially expressed genes were identified, of which 815 were up-regulated in TPF chemotherapy-responsive tissues whereas 764 were down-regulated. Gene ontology (GO) analysis suggested these genes participating in physiological processes including transcription and its regulation, cellular signal transduction and metabolic process. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) database revealed that MAPK and Jat/STAT signaling pathways occupied important roles in TPF chemotherapeutic sensitivity. Moreover, in vitro cell culture experiments revealed the expression alternations of IL-6, MAPK14, JUN, CDK5 and CAMK2A exposed to TPF treatment by qRT-PCR, whilst providing an insight into the mechanism underlying TPF chemotherapeutic response in HSCC. Conclusions: These results provided a battery of genes related to TPF chemotherapeutic sensitivity and might act as molecular targets in HSCC treatment. Moreover, these candidate biomarkers could contribute to HSCC individualized treatment.

Uncovering the multi-target pharmacological mechanism of Xuebijing injection against sepsis by a systems pharmacology approach

Sepsis is a life-threatening organ dysfunction that is associated with a high risk of death.Xuebijing(XBJ)injection,a Chinese herbal compound preparation,has been widely used for the treatment of sepsis in China.The purpose of this research is to decipher the underlying multi-target pharmacological mechanism of XBJ in the treatment of sepsis using a systems pharmacology approach.Compounds in XBJ were collected by literature retrieval.The corresponding putative targets of XBJ were screened from the Traditional Chinese Medicine Systems Pharmacology(TCMSP),Swiss Target Prediction(STP),and Search Tool for Interacting Chemicals(STITCH)databases.Sepsis-related targets were summarized using the Genecards,DrugBank,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection targets were obtained with Venny 2.1.Subsequently,protein-protein interaction(PPI)networks were constructed with the STRING database and Cytoscape 3.7.1.Then,degree,betweenness,and closeness were calculated to recognize the core targets in the PPI network.Moreover,the pharmacological mechanism of XBJ against sepsis was predicted via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.After the literature review,the 33 most commonly cited chemical ingredients,were screened out as major compounds.Bioinformatics analysis revealed that the major compounds of XBJ modulated 218 common targets associated with sepsis.Through PPI network analysis,41 genes,including IL-6,AKT1,STAT3,TP53,and MAPK1,were identified as core targets.The results of GO and KEGG enrichment revealed that the potential biological functions of XBJ against sepsis were mainly involved in cytokine receptor binding,cytokine activity,growth factor receptor binding,growth factor activity,and chemokine activity.The crucial pathways were closely associated with initial immune activation(CLR/TLR4-NF-κB/MAPK pathway),the acute inflammatory response(TNFMAPK/caspase and IL-MAPK/STAT pathways),and the late inflammation and coagulation process(HMGB1-RAGE and HIF-1 signaling pathways).This study revealed that the multiple components of XBJ exert multitarget effects against sepsis by regulating initial immune activation,the acute inflammatory response,and the late inflammation and coagulation process.

Miniaturized and highly sensitive fiber-optic Fabry–Perot sensor for mHz infrasound detection

Infrasound detection is important in natural disasters monitoring,military defense,underwater acoustic detection,and other domains.Fiber-optic Fabry–Perot(FP)acoustic sensors have the advantages of small structure size,long-distance detection,immunity to electromagnetic interference,and so on.The size of an FP sensor depends on the transducer diaphragm size and the back cavity volume.However,a small transducer diaphragm size means a low sensitivity.Moreover,a small back cavity volume will increase the low cut-off frequency of the sensor.Hence,it is difficult for fiber-optic FP infrasound sensors to simultaneously achieve miniaturization,high sensitivity,and extremely low detectable frequency.In this work,we proposed and demonstrated a miniaturized and highly sensitive fiber-optic FP sensor for m Hz infrasound detection by exploiting a Cr-Ag-Au composite acoustic-optic transducer diaphragm and a MEMS technique-based spiral micro-flow hole.The use of the spiral micro-flow hole as the connecting hole greatly reduced the volume of the sensor and decreased the low-frequency limit,while the back cavity volume was not increased.Combined with the Cr-Ag-Au composite diaphragm,a detection sensitivity of-123.19 dB re 1 rad∕μPa at 5 Hz and a minimum detectable pressure(MDP)of1.2 mPa∕Hz^(1∕2)at 5 Hz were achieved.The low detectable frequency can reach 0.01 Hz and the flat response range was 0.01–2500 Hz with a sensitivity fluctuation of±1.5 d B.Moreover,the size of the designed sensor was only 12 mm×Φ12.7 mm.These excellent characteristics make the sensor have great practical application prospects.