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ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer (PLGC) and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine (MNNG) solution (150 mg·L-1) for free drinking and gavage and ranitidine solution (0.03 g·kg-1) daily for 12 weeks. According to the random control table, mice were divided into a model group, a Qi-invigorating group (3.5 g·kg-1 of Astragali Radix), a blood-activating group (0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder), a Qi-invigorating and blood-activating group (3.5 g·kg-1 of Astragali Radix + 0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder), and a folic acid group (2 mg·kg-1). The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin (HE) staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 (LC3)Ⅰ, LC3Ⅱ, and Beclin1. Real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group, the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group, which were improved in all treatment groups, and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group, the content of LC3Ⅰ, LC3Ⅱ, LC3Ⅱ/LC3Ⅰ, and Beclin1 protein in gastric tissues of the model group was significantly decreased (P<0.05). As compared with the model group, the content of LC3Ⅰ, LC3Ⅱ, LC3Ⅱ/LC3Ⅰ, and Beclin1 protein in gastric tissues of each treatment group was increased (P<0.05, P<0.01). The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group, the mRNA expression of Beclin1 in the model group was decreased (P<0.05), and that of miR216b was increased (P<0.05). As compared with the model group, the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group (P<0.05), and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy, represented by Astragali Radix and Notoginseng Radix et Rhizoma, in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1, thus promoting autophagy and repairing gastric mucosa.
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OBJECTIVE@#To analyze clinical and genetic features of a family affected with Van der Woude syndrome.@*METHODS@#The umbilical cord blood of the proband and the peripheral blood of the parents were used for the whole exon sequencing to find the candidate gene.Peripheral blood of 9 members of the family were collected for Sanger sequencing verification, bioinformatics analysis and genotype-phenotype correlation analysis.@*RESULTS@#The proband was diagnosed with cleft lip and palate by ultrasound. His father and grandmother had hollow lower lip and all other family members did not have the similar phenotype. A missense c.263A>G (p.N88S) mutation was found in exon 4 of gene in the proband, his father and his grandmother.The mutation was not found in other family members.@*CONCLUSIONS@#A missense c.263A>G (p.N88S) mutation in gene probably underlies the pathogenesis of Van der Woude syndrome in the family and the mutation has been firstly discovered in China.
Subject(s)
Female , Humans , Male , Abnormalities, Multiple , Genetics , China , Cleft Lip , Diagnostic Imaging , Genetics , Cleft Palate , Diagnostic Imaging , Genetics , Cysts , Genetics , Interferon Regulatory Factors , Genetics , Lip , Congenital Abnormalities , Mutation , Pedigree , UltrasonographyABSTRACT
Immunotherapy has become an important treatment for melanoma.The anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor is safe and effective for melanoma patients with autoimmune disease (AD).However, when such patients are treated with anti-CTLA-4 antibody or PD-1/PD-L1 inhibitors, their condition changes should be closely monitored to prevent and avoid possible AD progression and immune-related adverse events.
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Targeted therapy such as the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)has made huge progress in treatment of non-small cell lung cancer (NSCLC).However,the emergence of acquired drug resistance is an inevitable result of the targeted therapy.The hepatocyte growth fac-tor/c-mesenchymal-epithelial transition factor (HGF /c-Met)signaling pathway participates in cell formation, migration,angiogenesis and other important cellular processes of multiple tumors.The abnormal activation of this signaling pathway plays the pivotal role in the acquired resistance to EGFR-TKI.Recently,some clinic tri-als prove that HGF /c-Met inhibitors can make clinical benefit of some NSCLC patients with acquired drug re-sistance of EGFR-TKI.
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<p><b>OBJECTIVE</b>To study the effect and mechanism of bevacizumab on proliferation and invasion of human lung cancer A549 cells.</p><p><b>METHODS</b>A549 cells were treated with bevacizumab. Proliferation and invasion of the bevacizumab-treated A549 cells were detected using cell counting kit CCK-8 and Transwell assay, respectively. The expression of the mRNA and protein of MMP-2, MMP-9 and c-Met were detected by real-time PCR and Western blotting, respectively.</p><p><b>RESULTS</b>Proliferation activity was inhibited at the concentration of 10 µg/ml and promoted at the concentration of 100 µg/ml bevacizumab. Bevacizumab in the concentration of 50 µg/ml had a stronger inhibitory effect on the invasion of A549 cells (16 406.19 ± 5 674.23 penetrated cells) than that of control group (36 108.68 6 263.83, P<0.05). The real-time PCR showed that bevacizumab had a stronger inhibitory effect on the expression of MMP-2 and MMP-9 mRNA at the concentration of 50 µg/ml and on the expression c-Met mRNA at the concentration of 10 µg/ml bevacizumabin the A549 cells. However bevacizumab at the concentration of 100 µg/ml showed a promoting effect on the expression of MMP-2, MMP-9 and c-Met mRNA (1.82 ± 0.31, 1.60 ± 0.25, 2.63 ± 0.48), significantly higher than that of the control group (1.00 ± 0.19, 1.00 ± 0.23, 1.00 ± 0.22, P<0.05). The expression of MMP-2, MMP-9 and c-Met mRNA and protein was inhibited by 10 µg/ml bevacizumab in a time-dependent manner. The Western blot assay showed that bevacizumab had a bi-directional effect on the expression of MMP-2 and c-Met proteins in the A549 cells: a promoting effect at 100 µg/ml and inhibitory effect on the expression of MMP-2 at 50 µg/ml bevacizumab, and inhibitory effect on the expression of c-Met protein at 10 µg/ml bevacizumab.</p><p><b>CONCLUSIONS</b>Our findings indicate that in a certain range of concentrations, bevacizumab has prominent inhibitory effect on the proliferation and invasion of A549 cells. However,over the concentration of 100 µg/ml, bevacizumab shows a weakening anti-invasion effect, even has a promoting effect on cell proliferation. This phenomenon may be related to the inhibiting effect on the expression of MMP-2 and c-Met proteins in a non-concentration-dependent manner by bevacizumab.</p>
Subject(s)
Humans , Angiogenesis Inhibitors , Pharmacology , Bevacizumab , Pharmacology , Blotting, Western , Cell Line, Tumor , Cell Movement , Cell Proliferation , Enzyme Inhibitors , Pharmacology , Lung Neoplasms , Metabolism , Pathology , Matrix Metalloproteinase 2 , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Neoplasm Invasiveness , Proto-Oncogene Proteins c-met , Metabolism , RNA, Messenger , Metabolism , Real-Time Polymerase Chain ReactionABSTRACT
To establish the HPLC fingerprints of Eucommia ulmoides at different ages of different varieties with pi-noresinol diglucoside as the reference material to provide the basis for the HPLC fingerprints in the enterprise quality standards of Eu-commia ulmoides from the GAP base of Chenzhou Dacheng Chinese Herbal Medicine Co. Ltd. . Methods: A column of ZORBAX E-clipse XDB-C18 (250 mm × 4. 6 mm, 5μm) was used. The mobile phase consisted of methanol-0. 1% phosphoric acid with gradient e-lusion. The detection wavelength was 277 nm, the column temperature was 25℃,the flow rate was 1. 0 ml·min-1 , and the injection volume was 5 μl. Results:The Eucommia ulmoides HPLC fingerprints including 14 common peaks were established with pinoresinol diglucoside as the reference material. The similarity of the HPLC fingerprints of 10 samples was over 0. 939. Conclusion:The method is accurate and reliable. The HPLC fingerprints can be used as the enterprise quality standards of Eucommia ulmoides for Chenzhou Dacheng Chinese Herbal Medicine Co. Ltd. .
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Livin,a novel member of human inhibitor of apoptosis protein family,is highly expressed in various malignant tumors. It plays an important role in the initiation,development,treatment and prognosis of tumors.Many studies have proved that down-regulation of Livin expression using RNA interference technique can reduce tumor growth,increase the apoptotic rate,and sensitize tumor cells to radiotherapy and chemo therapy.Full-length Livin is cleaved by the effector caspases to produce a truncated form (tLivin) with apoptosis-promotion activity.tLivin provides a new direction for the treatment of the malignant tumors.
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Matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) are gelatinases of matrix metalloproteinase family,which play a crucial role in the cancer cell growth,differentiation,invasion,migration,the regulation of tumour angiogenesis and immune surveillance because of their ability to degrade extracellular matrix proteins.So they are significantly associated with development and progression of various tumors.In recent years,the inhibitors and drugs against MMP-2 and MMP-9 arouse wide concern.
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Livin, a novel human inhibitor of apoptosis protein family member, participates in the regulation of apoptosis through inhibition of caspases and activation of mitogen activated protein kinase ( MAPK )and other pathways. Livin is over-expressed in many tumors and plays an important role in the initiation and development of tumor, providing a promising new field of cancer research.
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Dendritic cells(DC)present telomerase reverse transcriptase(hTERT)to T lymphocytes, stimulating specific reactions of cytotoxic T cells and CD4 + T cells. Researches on the relationship between natural killer(NK)cells and telomerase of tumor cells are scarce. DC and NK cells act together promoting antitumor responses and possibly participate in anti-tumor immune responses with telomerase.
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Objective To incestigate the fetures of cranial CT and MRI in the patients with hypertensive encephalopathy. Methods The CT and MRI findings of ten cases of hypertensive encephalopathy with the charge of CT,MRI appearance of FLAIR (fluid attenvated inversion-recovery), DWI(difussion weighted imaging),ADC(apparent diffusion coefficient) were analyzed retrospectively. Results Of ten patients,3 cases had abnormal finding in the cranial CT;10 cases had abnormal finding in the cranial MRI,the lesions were demonstrated as slightly hypointensity on T1WI and slightly hyperintensity on T2WI and remarkably hyperintensity on FLAIR,and iso or slightly hyperintensity on DWI,and remarkably hyperintensity on ADC.The lilateral parietal occipital lobes and cerebellar hemisphere and Brain Stem were the more common sites. Conclusions The only characteristric finding of hypertensive encephalopathy in MRI and CT imaging studies is vasogenic edema,especially in the subcortical white matter of the parietal and occipital lobes bilaterally,and cereballar hemisphere et al;especially FLAIR,DWI and ADC of MRI can be helpful for diagnosis and diffenential diagnosis,prognosis and curative effect of hypertensive encephalopathy.
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Background and purpose:Nowadays, the golden standard of diagnosis for malignant hydrothorax or ascites is exfoliocytology examination, but the missed diagnosis rate is too high. Other methods including immunologic test, telomerase activation test, conjugation of chromosome analysis with cytological examination test, and RT-PCR test. But none of them was widely used due to high cost or high false positive rate. Immunomagnetic beads (IMB) technique is a popular method all over the world in recent years. It was mainly used in isolating and purifying cells, but it was rarely used to detect cancer cells in patients with hydrothorax or ascites so far. Our aim was to fi nd an effi cient way to detect the cancer cells in patients with cancer related hydrothorax or ascites and to improve the corresponding diagnosis rate. Methods:In the experiments, both the traditional exfoliocytology examination method and IMB technique were used to detect the cancer cells in the hydrothorax or the ascites for comparison. Results:Using IMB technique and exfoliocytology method, the positive rates in 30 patients with cancers were 63.3% (19/30) and 23.3% (7/30), respectively, and the false positive rates in 30 patients without cancers were 3.3% (1/30) and 0.0% (0/30), respectively. It could be observed that the positive rate using IMB technique was much higher than that using exfoliocytology method (P0.05). Conclusions:The present study demonstrated that IMB technique is an accurate, sensitive, fast and economic method in detecting the cancer cells in patients with cancer related hydrothorax or ascites, especially for diagnosis and therapy in the early clinical stage. Due to the high effi ciency, IMB technique could be used after exfoliocytology examination to improve the diagnosis rate..
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AIM: Shengdeye is a kind of medicinal wine. It is fermented with 30 kinds of medicinal herbs such as glossy ganoderma, pilose antler, panax, medlar and sorghum. This study aimed to observe the effects of Shengdeye on anti-fatigue and memory in mice.METHODS: The mice were fed with Shengdeye 5 ml*kg-1 and 2.5 ml*kg-1 2 times per day. After 7 days, the mice were examined on anoxia-resistant and swimming test for anti-fatigue and step down test for memory.RESULTS: The anoxia-resistant of shengdege group was apparently longer than that of the control group [(29.60±1.36) min vs (24.40±3.13) min, P<0.01], and the swimming time was sharply increased [(142.6±53.8) min for 2.5 ml*kg-1 and (162.9±43.5) min for 5 ml*kg-1 vs (94.9±39.1) min, P<0.05]. The error times of shengdege group was lower than that of the control [(1.5±1.4) times and (2.3±1.3) times vs (3.7±1.1) times, P<0.01]. The delitescence of two group were sharply prolonged [(136.8±50.1) s, and (128.0±41.5) s vs (50.2±42.9) s, P<0.01].CONCLUSION: The results indicated that Shengdeye had an anti-fatigne effect and increased the faculty of memory. The experiment of acute toxicity showed that the medicinal herbs in Shyengdeye were safe.