1.High expression of CRTAC1 promotes proliferation, migration and immune cell infiltration of gastric cancer by regulating the PI3K/AKT signaling pathway.
Fuxing ZHANG ; Guoqing LIU ; Rui DONG ; Lei GAO ; Weichen LU ; Lianxia GAO ; Zhongkuo ZHAO ; Fei LU ; Mulin LIU
Journal of Southern Medical University 2024;44(12):2421-2433
OBJECTIVES:
To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC.
METHODS:
Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism.
RESULTS:
Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (P<0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (P<0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (P<0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells.
CONCLUSIONS
High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition via modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.
Stomach Neoplasms/metabolism*
;
Humans
;
Cell Proliferation
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Phosphatidylinositol 3-Kinases/metabolism*
;
Signal Transduction
;
Cell Movement
;
Cell Line, Tumor
;
Prognosis
;
Apoptosis
;
Tumor Microenvironment
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Female
;
Male
;
Epithelial-Mesenchymal Transition/genetics*
2.Research Status of Endothelialization of Poly (ε-caprolactone) Small-Caliber Vascular Graft Implanted in Animals
Jiali YANG ; Jinyan LU ; Weichen ZHANG ; Xiaoyan DENG ; Hongyan KANG
Journal of Medical Biomechanics 2021;36(2):E317-E323
The most serious problem facing the implantation of vascular graft in the body is the formation of blood clots. In order to solve this problem, various attempts have been made by the scientific community for many years. However, endothelialization is the fundamental method to solve thrombosis and keep vascular graft open for a long time. Poly (ε-caprolactone) (PCL) has the advantages of biodegradability, low cost and good mechanical properties. In recent years, it has been widely used as tissue engineering scaffolds, drug deliverys and so on. This article mainly reviews the endothelialization of small-caliber vascular graft based on PCL after implanted in different animal models, as well as the endothelialization of the same animal model but under different implantation conditions, and trying to find the reasons why small-caliber vascular grafts are still not ideal in clinical applications at different angles such as the different animal models and the different way about endothelialization, and provide references for future animal model selection.
3.Efficacy of bupivacaine pamoate for sciatic nerve block in rats
Jingjing LIU ; Dengjun CHEN ; Yihua WANG ; Xin JIN ; Hongxiu PAN ; Xiaorong LU ; Weichen ZHOU
Chinese Journal of Anesthesiology 2021;41(10):1242-1246
Objective:To evaluate the efficacy of bupivacaine pamoate for sciatic nerve block in rats.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, weighing 300-400 g, were divided into 6 groups using a random number table method: bupivacaine pamoate vehicle group (group VE), bupivacaine HCl group (group BH), liposomal bupivacaine group (group BL), low-dose bupivacaine pamoate group (group HL), moderate-dose bupivacaine pamoate group (group HM) and high-dose bupivacaine pamoate group (group HH), with 8 animals in each group.In VE, BH, BL, HL, HM and HH groups, bupivacaine pamoate vehicle 0.4 ml, bupivacaine HCl solution 0.4 ml, liposomal bupivacaine suspension 0.4 ml, and 1, 3 and 10 mg/ml bupivacaine pamoate suspension 0.4 ml were injected around the left sciatic nerve, respectively.The thermal paw withdrawal latency were measured before administration (T 0) and at 0.5, 1.5, 3, 5, 8, 12, 16, 24 and 48 h after injection (T 1-9). The percentage of maximum possible effect (MPE) of thermal paw withdrawal latency was calculated, and motor function score was simultaneously performed to evaluate the efficacy of sensory and motor block.Five and three rats in each group were sacrificed at 2 and 7 days after administration (T 9, 10), respectively, and the sciatic nerve at the injection site and the surrounding muscle tissues were harvested for microscopic examination (with a light microscope) after Luxol fast blue and HE staining.Nerve damage and inflammatory responses were assessed and scored to evaluate neurotoxicity. Results:Compared with group VE, the MPE was significantly increased at T 1-4 in group HL, at T 1-8 in group HM and at T 1-8 in group HH, the motor function scores were decreased at T 1-4 in group HL, at T 1-5 in group HM and at T 1-7 in group HH ( P<0.05), and no significant change was found in inflammatory response scores for the sciatic nerve and surrounding muscles at each time point in HL, HM and HH groups ( P>0.05). Compared with group BH, the MPE was significantly increased at T 3-8, motor function scores were decreased at T 3-5, and inflammatory response scores for the muscles around the sciatic nerve were decreased at T 9 in group HM ( P<0.05). Compared with group BL, the MPE was significantly increased at T 3-7, motor function scores were decreased at T 4, 5, and inflammatory response scores for the sciatic nerve and surrounding muscles were decreased at T 9 in group HM ( P<0.05). The nerve damage score was 0 in the six groups. Conclusion:Bupivacaine pamoate can block the sciatic nerve of rats, the duration of block is prolonged with the increase in the concentration, and the duration of motor block is not longer than that of sensory block; compared with the same concentration and equal volume of bupivacaine HCl and liposomal bupivacaine, bupivacaine pamoate produces longer duration of sciatic nerve block and less neurotoxicity.
4. Experimental study on the inhibitory effect of soap solution on rabies viruses
Shuqing LIU ; Qian WANG ; Yanrong LI ; Xiaoyan TAO ; Pengcheng YU ; Xuexin LU ; Weichen WU ; Jianghong YAN ; Wuyang ZHU
Chinese Journal of Experimental and Clinical Virology 2017;31(3):227-231
Objective:
To investigate the inactivating effect of soap solution on rabies virus and to explore the concentration of soap solutions which could be effective in post-exposure prophylaxis (PEP) of rabies virus infection.
Methods:
The BSR and N2a cells were respectively infected by the mixture of different concentrations of soap solution and rabies virus CVS-11. Based on the direct immunofluorescent method (DFA) and reverse transcription PCR (RT-PCR), the inactivating effects of soap solutions on rabies viruse in BSR and N2a cells were detected, respectively.
Results:
This experiment established the BSR or N2a cells model in 24 well cell culture plates, and we found that the upper limit of soap solution concentration which BSR or N2a cells could tolerate was 1%. The inhibitory effect test of different soap solution on rabies virus showed that the 0.5% concentration of soap solution could completely inhibit the survival of CVS-11 strain in both the BSR and N2a cells, but the 0.1% concentration of soap solution could not inhibit the rabies viruses completely.
Conclusions
The 0.5%-1% concentration of soap solutions could inhibit the survival of CVS-11 strain in three minutes in vivo experiment.
5.Genome Architecture and Its Roles in Human Copy Number Variation.
Lu CHEN ; Weichen ZHOU ; Ling ZHANG ; Feng ZHANG
Genomics & Informatics 2014;12(4):136-144
Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs), are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.
Base Sequence
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DNA
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DNA Copy Number Variations
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DNA Replication
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DNA Replication Timing
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Genome*
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Genome, Human
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Genomic Instability
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Humans
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Mutagenesis
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Recombination, Genetic
6.Localizing the focus of ischemic stroke with near infrared spectroscopy.
Weiguo CHEN ; Guang LU ; Wemara LICHTY
Chinese Medical Journal 2002;115(1):84-88
OBJECTIVETo evaluate the changes in near infrared spectroscopy (NIRS) absorptive properties induced by cerebral ischemia.
METHODSA dual wavelength (760 nm and 850 nm) NIRS system measuring total hemoglobin concentration changes was constructed. Twenty Sprague-Dawley rats were used to set up middle cerebral artery occlusion (MCAO) model that had a stable ischemia focus on the cortex. We used NIRS to localize the ischemia focus that was confirmed with magnetic resonance imaging (MRI) and triphenyltetrazonlium chloride brain staining. The cortical ischemia area and the geometric configuration of the NIRS topograms were compared with those from MRI and the anatomical samples for the same rat.
RESULTSThe reconstructed NIRS topograms showed that there was an optical density decreased area on the left cortex of the rats with MCAO model. The mean ischemia area as shown in NIRS images was 19.50 mm2 (19.50 +/- 0.35 mm2, n = 20). Anatomical samples showed that the mean ischemic area located in the NIRS measurement area was 18.46 mm2 (18.46 +/- 0.38 mm2, n = 20). For MRI, the mean ischemia area located in the NIRS measurement area was 20.71 mm2 (20.71 +/- 0.27 mm2, n = 20). There were no significant differences among NIRS, MRI and anatomical samples (F(2,57) = 2.47, P > 0.05) for defining the ischemia area. The results showed that there was a significant correlation among NIRS, MRI (r = 0.782, P < 0.05) and anatomical sample (r = 0.851, P < 0.05) for the same cortical ischemia area. Meanwhile, the location and geometric configuration of the ischemia focus shown by NIRS were identified by MRI and anatomical samples, though the NIRS images had worse spatial resolution.
CONCLUSIONSNIRS showed a good agreement with MRI and anatomical samples in the ischemic area and location determination of the infarction focus for the rat MCAO model. The study suggests that NIRS can non-invasively trace cortical hemodynamic changes induced by ischemia in real time.
Animals ; Brain Ischemia ; diagnosis ; Magnetic Resonance Imaging ; Male ; Rats ; Rats, Sprague-Dawley ; Spectroscopy, Near-Infrared

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