ABSTRACT
Objective To explore the differentially expressed mRNAs and related biological processes and pathways in fractional low-dose ionizing radiation (LDIR)-induced senescence of normal human bronchial epithelial (HBE) cells by high-throughput mRNA sequencing and bioinformatics techniques. Methods Senescence-associated β-galactosidase staining and senescence-associated secretion phenotype gene mRNA and protein expression levels were measured at 24 and 48 h after irradiating HBE cells 7 times at doses of 0, 50, 100, and 200 mGy, respectively. The differentially expressed genes were screened by high-throughput sequencing for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results The senescence-positive area of fractional low-dose irradiated HBE cells increased in a dose-dependent manner (P < 0.05). The mRNA levels and protein expression of transforming growth factor-β1(TGF-β1) and matrix metalloproteinase-9(MMP-9) genes were increased in the 100 mGy × 7 and 200 mGy × 7 groups at 24 and 48 h after the end of irradiation compared with the control group. High-throughput sequencing showed that there were 882, 475, and 1205 differentially expressed mRNAs in each dose group compared with the control group. GO analysis showed that the differentially expressed mRNAs in each dose group were mainly enriched in biological processes such as cell cycle regulation, regulation of nitrogen compound metabolic process, regulation of cell division and response to stimulus. KEGG analysis showed that the differentially expressed mRNAs were mainly enriched in the pathways of cell cycle, cell senescence, and ferroptosis. Conclusion Fractional LDIR induced senescence in HBE cells, and differentially expressed mRNA-associated biological processes and pathways in senescent cells are related to cell cycle and cell senescence.
ABSTRACT
In recent years, endovascular therapy has become the most important progress in the field of the treatment of acute ischemic stroke caused by large vessel occlusion. However, the vascular recanalization shown by imaging after endovascular treatment cannot fully translate into effective tissue reperfusion and functional outcome, a phenomenon known as "futile recanalization". Combined neuroprotective therapy after vascular recanalization is expected to reduce the occurrence of futile recanalization and improve the outcome of patients. This article briefly summarizes the main application progress of commonly used neuroprotective therapies in clinical practice (edaravone dexborneol, glucocorticoids, hypothermia, and remote ischemic conditioning). It explores the trend and direction of combining endovascular therapy and neuroprotective therapy for patients with acute ischemic stroke caused by large vessel occlusion, and provides further reference and suggestions for intervention measures after endovascular therapy.
ABSTRACT
Objective To investigate the mechanism of fractionated low-dose ionizing radiation (LDIR) in the induction of EA.hy926 cell senescence. Methods EA.hy926 cells were irradiated with X-ray at 0, 50, 100, and 200 mGy × 4, respectively, and cultured for 24, 48, and 72 h. Several indicators were measured, including the levels of cellular senescence-associated β-galactosidase (SA-β-gal) staining, mRNA levels of senescence-associated cell cycle protein-dependent kinase inhibitor genes CDKN1A and CDKN2A, reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and phosphorylated H2A histone family member X (γ-H2AX). Results After 4 fractionated LDIR, compared with the control group, the treatment groups showed increased nucleus area, blurred cell edge, and increased SA-β-gal positive area (P < 0.05) at 24, 48 and 72 h. After 4 fractionated LDIR, the mRNA level of CDKN1A increased in the 100 and 200 mGy × 4 groups at 24 and 48 h (P < 0.05), and CDKN2A mRNA level increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). The fluorescence intensity of ROS increased in treatment groups at 24, 48, and 72 h after 4 fractionated LDIR (P < 0.05). After 4 fractionated LDIR, the T-AOC level increased in the 100 and 200 mGy × 4 groups at 24 h (P < 0.05), and T-AOC level increased in all treatment groups at 48 and 72 h (P < 0.05). After 4 fractionated LDIR, γ-H2AX fluorescence intensity increased in all treatment groups at 24 h (P < 0.05), and the fluorescence intensity increased in the 100 and 200 mGy × 4 groups at 48 and 72 h (P < 0.05). Conclusion Fractionated LDIR can induce cellular senescence in EA.hy926 cells by impacting the cellular oxidation-antioxidation and oxidative damage levels, and the effects were relatively evident at 100 and 200 mGy.
ABSTRACT
Background Radiation-induced liver damage is a major complication for primary liver cancer and other upper abdominal tumors during radiation therapy. The early biological effects of radiation-induced liver damage at different doses of radiation and its mechanisms of action have not yet been elucidated. Objective To establish X-ray-induced radioactive mouse liver damage model and explore the level of oxidative stress and its correlation with nuclear factor-κB (NF-κB) and transforming growth factor-β1 (TGF-β1). Methods A total of 24 male C57BL/6J mice aged 6 weeks were randomly divided into 4 groups (control, 0.8 Gy, 1.6 Gy, and 4 Gy), with 6 mice in each group. X-rays irradiated the whole body of mice singly in each dose group. At 24 h after radiation, histopathological changes in mouse liver were evaluated; peripheral blood cell count, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as liver tissue superoxide dismutase (SOD) activity, malondialdehyde (MDA) level, reduced glutathione (GSH) level, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) level were measured; real-time fluorescence quantitative PCR was used to detect liver tissue NF-κB p65 and TGF-β1 mRNA expression levels; the correlations of oxidative stress indicators with NF-κB p65 and TGF-β1 mRNA expression levels were analyzed by Pearson correlation. Results Compared with the control group, at 24 h after different doses of X-ray radiation, early injury-related histopathological changes were observed in liver, and the serum levels of AST and ALT were significantly increased in the 4 Gy group (P<0.05); the numbers of peripheral blood leukocytes and lymphocytes were decreased in the radiation exposure groups (P<0.05), showing a decreasing trend with increasing radiation doses; the levels of liver oxidative stress indicators (MDA, SOD, and GSH) in exposed mice were significantly increased (P<0.05), showing an increasing trend with increasing radiation doses. The liver 8-OHdG were significantly increased in the 1.6 Gy and 4 Gy groups compared with the control and the 0.8 Gy groups, respectively (P<0.05). The NF-κB p65 and TGF-β1 mRNA expression levels in the liver of mice were significantly increased in the 1.6 Gy and 4 Gy groups compared with the control group (P<0.05). The TGF-β1 mRNA expression level also exhibited an increasing trend with increasing radiation doses. The results of correlation analysis showed that the levels of MDA, SOD, GSH, and 8-OHdG in liver tissues were significantly and positively correlated with the expression levels of NF-κB p65 and TGF-β1 mRNA (P<0.05). Conclusion X-rays of various doses can affect the degree of liver injury, peripheral blood cell count, serum levels of AST and ALT, and liver oxidative stress levels in mice. The level of oxidative stress induced by X-ray is positively correlated with NF-κB and TGF-β1 in liver tissues, and it may participate in the process of radiation-induced liver injury.
ABSTRACT
Background The thyroid gland is one of the organs sensitive to ionizing radiation, and there are few studies on the effects of long-term exposure to low doses of ionizing radiation on the thyroid gland of radiation workers. Objective To investigate thyroid abnormalities in workers in medical radiology departments in Guangdong Province and to identify potential influencing factors of thyroid abnormalities. Methods A total of 1657 radiation workers from 48 hospitals in Guangdong Province were selected as survey subjects using convenience sampling, and their personal dose monitoring results and health examination information were retrospectively analyzed to determine the factors affecting thyroid abnormalities. Results The M (P25, P75) of thyroid absorbed dose (DT) was 1.55 (0.65, 3.96) mGy in the 1657 investigated workers. The attribute-specific medians of DT were 1.29, 1.38, 1.99, and 3.51 mGy for departments of diagnostic radiology, interventional radiology, radiotherapy, and nuclear medicine, respectively; and 1.10, 1.55, and 1.80 mGy for job titles of nurse, technician, and physician, respectively. Differences in DT by gender, age, years of radiological work, age of radiation exposure onset, occupational category, and job title were statistically significant (Z=−6.35, H=708.52, 918.20, 31.19, 95.64, 39.28, P<0.05). The positive rate of thyroid abnormalities in investigated workers was 46.53% (771/1657). Among them, the positive rate of abnormal thyroid function was 22.87% (379/1657), that of abnormal thyroid morphology was 33.98% (563/1657), and that of thyroid nodule was 26.55% (440/1657). The differences in thyroid abnormality rates by gender, age, years of radiation work, age of radiation exposure onset, DT, and job title of radiation workers were statistically significant (χ2=51.89, 49.64, 20.54, 18.29, 12.07, 16.16, P<0.05). The differences in abnormal thyroid function positive rate by gender, age of radiation exposure onset, and job title were statistically significant (χ2=26.21, 6.21, 8.32, P<0.05). The differences in the positive rates of abnormal thyroid morphology and nodules were statistically significant by gender, age, years of radiological work, age of radiation exposure onset, DT, and job title (abnormal thyroid morphology, χ2=40.24, 64.17, 37.63, 15.17, 19.28, 15.05; nodules, χ2=31.41, 77.98, 42.11, 19.16, 21.70, 13.52, P<0.05). The positive rates of thyroid abnormality, thyroid morphology abnormality, and nodules all showed a linear increasing trend with increasing age, years of radiation work, and age of radiation exposure onset (P<0.05). The results of logistic regression analysis indicated that the factors influencing thyroid abnormalities were female (OR=2.17, 95%CI: 1.72-2.74), increased years of radiological work (OR=1.04, 95%CI: 1.03-1.06), onset of radiation exposure in age groups of 30-34 and ≥35 years (OR=1.63, 95%CI: 1.12-2.37; OR=2.58, 95%CI: 1.74-3.29), and working in department of diagnostic radiology (OR=1.40, 95%CI: 1.07-1.84). Conclusion Long-term exposure to low doses of ionizing radiation has an effect on thyroid abnormalities in medical radiation workers. Among them, being female, physicians, and working in department of diagnostic radiology are at a higher risk of abnormal thyroid function; being female, increased years of radiation work, and radiation exposure onset at age ≥30 years are associated with a higher risk of reporting abnormal thyroid morphology.
ABSTRACT
@#<b>Objective</b> To investigate the effects of lowdose ionizing radiation (LDIR) on oxidative stress and damage repair in human bronchial epithelial (HBE) cells. <b>Methods</b> HBE cells were divided into 0, 50, 100, and 200 mGy groups, and cultured for 24 and 48 h after X-ray irradiation, respectively. The cell viability, levels of glutathione (GSH), malondialdehyde (MDA), and 8-hydroxy-2’-deoxyguanosine (8-OHdG), and transcriptional levels of DNA damage repair genes <i>PPP2R2D</i> and <i>TP53</i> were measured. <b>Results</b> At 24 h after irradiation, there was no significant difference in the cell viability between the dose groups and the control group (<i>P</i> > 0.05); all dose groups had significantly increased MDA level, dose-dependently decreased GSH level, dose-dependently increased 8-OHdG level, and significantly increased mRNA level of <i>PPP2R2D</i> gene (all <i>P</i> < 0.05); the mRNA expression level of <i>TP53</i> gene was significantly increased in the 50 mGy group (<i>P</i> < 0.05). At 48 h after irradiation, there were the highest cell viability, significantly decreased MDA and 8-OHdG levels, and significantly increased mRNA expression levels of <i>PPP2R2D</i> and <i>TP53</i> genes in the 50 mGy group compared with the control group (all <i>P</i> < 0.05); the GSH level in the 100 mGy group was significantly increased (<i>P</i> < 0.05). <b>Conclusion</b> LDIR, especially radiation at 50 mGy, can affect the oxidative-antioxidant level in HBE cells and the transcript-level differential expression of DNA damage repair genes.
ABSTRACT
ObjectiveTo establish a method for seahorse identification based on graphene oxide fluorescence sensing technology, and to provide a new research idea for identification of traditional Chinese medicine. MethodThe fluorophore FAM was labeled at the 5' end of the specificity upstream primer Ja-F of Hippocampus japonicus as the nucleic acid probe FAM-ssDNA (single strand DNA). The recognition site of RNA polymerase Ⅱ was added to its specific downstream primer Ja-R as Ja-R1. The seahorse samples were amplified with Ja-F/Ja-R1 primers, and the ssDNA of H. japonicus was obtained by reverse transcription of the amplification products using vitro transcription method. The 20 μL nucleic acid probe FAM-ssDNA (500 nmol·L-1) was incubated at 90 ℃ for 5 min, and was gradually cooled to room temperature. Different volume of graphene oxide solution (100 mg·L-1) and Tris hydroxymethyl amino methane HCl (Tris-HCl) buffer (50 mmol·L-1) were added into each probe solution to make a final reaction volume of 1 mL. The fluorescence intensity of each sample was measured after mixing and placing different times at room temperature away from the light. So that the most appropriate graphene oxide concentration and reaction time were screened for constructing the best nucleic acid probe-graphene oxide biosensor. Adding probe complementary sequence FAM-ssDNA-match solution into the nucleic acid probe-graphene oxide solution, the fluorescence intensity of the reaction mixture was measured after being placed different times at room temperature. Therefore, the optimal reaction time of fluorescence recovery was screened and the feasibility of the sensor was tested. The sensitivity was detected via adding ddH2O as the blank control and different concentration H. japonicus ssDNA into each nucleic acid probe-graphene oxide solution, respectively. Finally, the commercial hippocampal were identified using the optimal experimental condition, and the feasibility of this method for the identification of Chinese medicinal materials was verified. ResultThe fluorescence of 1 mL reaction mixture including 10 nmol·L-1 nucleic acid probe FAM-ssDNA and 12 mg·L-1 go solution for 20 min at room temperature away from the light could be completely quenched. Feasibility test of the biosensor showed that when probe complementary sequence FAM-ssDNA-match solution (final concentration 90 nmol·L-1) was added to the biosensor solution and reacted 1 h reaction at room temperature, the fluorescence signal was significantly enhanced. Sensitivity test showed that the minimum concentration of ssDNA detected by this method was about 10 mg·L-1. This method was used to detect commercial seahorses, and only H. japonicus samples had obvious fluorescence signal. ConclusionThe graphene oxide-based fluorescent sensing technology could be used for zoological origin survey of commercial hippocampus.
ABSTRACT
[Objective]To explore the connotation and feasibility of prevention and treatment of monkeypox by traditional Chinese medicine(TCM),in order to reduce the public health pressure and economic loss caused by the transmission of monkeypox virus,and to formulate effective prevention and treatment strategies.[Methods]Based on the outbreak of monkeypox in several non-monkeypox endemic areas in the world,with reference to the relevant reports and research results of monkeypox at home and abroad,the epidemic prevention experience of TCM in the past thousand years was sorted out.According to the pathogenesis and clinical manifestations of monkeypox,the category of monkeypox in TCM was analyzed.This paper analyzed the related literature of ancient and modern diseases,and explored the methods of preventing monkeypox with TCM.[Results]TCM believes that monkeypox belongs to the category of sore rash and pox rash.It is believed that the pathogenesis of monkeypox focuses on the deficiency of healthy Qi,weak Wei Qi(the deficiency),because of bad behavior or other contact conditions touching the evil,that is,the sense of"improper Qi",hidden within the body and develops later.The pathogenesis of monkeypox is divided into cold and heat,and heat is still the main pathogenic factor.In the course of disease prevention and treatment,it should be based on"clear rash and remove pathogenic factor",with stage differentiation and treatment,adopting the method of clearing plague and detoxification,emphasizing the importance of strengthening the root,paying attention to prognosis,paying attention to emotional therapy and careful protection.[Conclusion]TCM does have advantages in the prevention and treatment of epidemic rash.It can further promote scientific research,give full play to the unique advantages of TCM,provide reference for the prevention and control of monkeypox epidemic,reduce public health pressure,and promote the progress of disease research.
ABSTRACT
Objective @# To investigate the role of Epac1 / CaMK Ⅱ signaling pathway in myocardial ischemia reper- fusion injury (MIRI) in mice,and to investigate the protective effect of vitexin ( VT) on acute MIRI.@*Methods@#C57 / BL mice were randomly divided into 5 groups : Sham surgery group ( Sham) ,ischemia reperfusion group ( I / R) ,and ischemia reperfusion + vitexin group ( function 3,6,12 mg / kg groups) .Ligation of the left anterior descending coronary artery (LAD coronary artery) in mice resulted in ischemia of part of the heart tissue for 30min and reperfusion of the blood for 120min.Mouse myocardial ischemia reperfusion injury ( MIRI) model was established.In the sham operation group,only the LAD was not ligated.Serum LDH levels of mice were detected.Hema- toxylin-eosin (H&E) staining was performed on the left ventricular myocardium of mice to observe the histopatho- logical changes.The expression level of Epac1 in myocardial tissue was observed by immunohistochemistry.The protein expressions of Epac1,Rap1,CaMK Ⅱ and ERK / p-ERK were determined by Western Blot. @*Results @# Compared with Sham group,serum LDH level of mice in I / R group was significantly increased,protein expressions of Epac1, Rap1 and CaMK Ⅱ in myocardial tissue were significantly up-regulated,and ERK1 /2 phosphorylation level was decreased.Compared with I / R group,vitexin (3,6,12 mg / kg) pretreatment group decreased serum LDH level,inhib- ited Epac1,Rap1 and CaMK Ⅱ protein expression in mouse myocardial tissue,and promoted ERK1 /2 phosphoryla- tion(P<0. 05 or P<0. 01) .The histopathological results showed that the myocardial fibers in the I / R group were disordered and broken,with increased gaps and obvious inflammatory cell infiltration.In the vitexin treatment group,the myocardial fibers were arranged more neatly and inflammatory cells were infiltrated less.@*Conclusion@#Vitexin may regulate Epac1 / CaMK Ⅱ signaling pathway,down-regulate CaMK Ⅱ protein expression,increase ERK phosphorylation,and effectively reduce MIRI.
ABSTRACT
Purulent meningitis(PM)is the main reasons of infectious diseases in the central nervous system of children.It is one of the leading causes of neurological sequelae in children.Pathogens are related to region, socioeconomic status, environment, age, etc.The epidemiology has been changing owing to the increasing vaccination coverage rate.Streptococcus pneumoniae, Staphylococcus epidermidis, Escherichia coli and group B Streptococcus are the main pathogens of PM in children.Antibiotics are the main treatment.Corticosteroids are controversial in the treatment of PM.Vaccination is the main method to prevent PM and its complications.With the development of genetics, the genetic variation of immune system has been proved to be related to the susceptibility of PM.This article reviews recent advances in epidemiological changes, treatment, and genetic associations of PM in children.It is helpful for the diagnosis and treatment of PM.
ABSTRACT
Multiple system atrophy (MSA) is a rare and rapidly-progressive neurodegenerative disorder, characterized by the combination of dysautonomia, poor levodopa responsive parkinsonism, cerebellar ataxia, and pyramidal tract signs. Insidious onset, clinical heterogeneity and progression of the disease complicate the difficulty of early diagnosis and challenge, the development of neuroprotective drugs. In order to improve the knowledge of diagnosis and treatment of the disease, this paper reviews advances in its diagnostic criteria, biomarkers of early diagnosis and management of the disease.
ABSTRACT
Neurofilament light chain (NfL), a sensitive biomarker of axonal damage, was found increasing in several neurological diseases. Parkinsonism is a group of clinical syndromes characterized by cardinal symptoms of bradykinesia, rigidity, and tremor, including Parkinson′s disease (PD) and parkinsonism plus syndrome (PPS). It is difficult in the diagnosis and differential diagnosis of PD and PPS, especially in the early stage. Evidence suggests that NfL in the cerebrospinal fluid and blood is a promising biomarker for the differential diagnosis of PD and PPS. This article reviewed and summarized the research progress of value of NfL in PD and PPS, and proposed future research directions.
ABSTRACT
Objective:The causes of infertility are complex and diverse, and congenital adrenal hyperplasia (CAH) is often overlooked in screening for infertility. In this study, CAH was diagnosed in women with high androgenemia who were infertile during childbearing age, and the diagnosis and treatment of CAH in pregnant women was investigated.Methods:This study included 20 women with high androgenemia and infertility in the childbearing age who were referred to the Endocrinology Department after visiting the Reproductive Medicine Center of the First Affiliated Hospital of Nanjing Medical University from December 2016 to April 2019. All patients were tested for blood hormone levels, glucose, and lipid metabolism, underwent ACTH stimulation test, uterus and bilateral ovarian B-ultrasound, adrenal computed cosmography (CT), etc. Full-length sequencing of the CYP21A2 gene was performed as necessary.Results:Among the 20 women with hyperandrogenism who were infertile, there were 7 cases of CAH (35.0%), including 6 cases of 21-hydroxylase deficiency (21-OHD) confirmed by gene sequencing; 10 cases of polycystic ovary syndrome (PCOS); 3 cases of idiopathic hyperandrogenemia (IHA). Sex hormone results showed that testosterone in CAH group was significantly higher than that in PCOS group and IHA group [(4.4±2.0 vs 2.9±0.4, 2.8±0.8) nmol/L, P<0.05]; ACTH stimulation test showed that the 17-hydroxyprogesterone (17-OHP) in CAH group was significantly higher than that in PCOS group [(101.0±100.8 vs 1.4±0.8) ng/ml, P<0.05]. There was no significant difference between CAH group and IHA group [(101.0±100.8 vs 3.0±1.8)ng/ml, P>0.05]. However, the 17-OHP (60 min) in CAH group was significantly higher than that in PCOS group and IHA group [(200.1±80.8 vs 3.1±1.2, 3.4±0.2) ng/ml, P<0.05]. Glucocorticoid therapy was given to patients with CAH, and 4 patients had successful pregnancy. No clinical symptoms of CAH and external genital malformations were found in the offspring of patients who had been delivered. Conclusions:The ACTH stimulation test is of great significance in the differential diagnosis of CAH, especially 21-OHD. Genetic testing helps to identify the type of mutation in CAH patients. On the one hand, glucocorticoid therapy may improve the pregnancy rate of CAH patients, on the other hand, it can help to reduce the status of maternal high androgen and avoid masculine manifestation of female offspring.
ABSTRACT
Objective To investigate the effect of low salt diet on vascular remodeling of rat induced by high fructose(HF).Methods Wistar male rats weighed 180-200 g were fed for 8 weeks and randomly divided into 6 groups:(1) control group was given the normal fodder and distilled water;(2) high fructose group(HF) was given normal fodder (0.5 % NaCl,w/w) and fructose water(10 %,w/v);(3) high-salt group (HNa) was given high salt fodder (7 % NaCl,w/w) and distilled water;(4) high fructose combined with high salt diet group(HFNa) was simultaneously given high salt fodder and 10 % fructose water;(5)high fructose combined low salt group(HFLNa) was simultaneously given low salt fodder and 10% fructose water;(6) high fructose combined with spirotaclone group(HFE) was given 10% fructose water for 4 weeks and then added with spirotaelone(50 mg · kg-1 · d-1 by tube feeding) for continuous 4 weeks.The changes of arterial blood pressure,vascular wall histological evaluation and expression of α-SMA and fibronectin in vascular wall were detected in each group.Results (1) Compared with the blood pressure[(111.03 ±9.17) mm Hg] in the control group,the blood pressure in the HF and HNa groups were (133.94± 5.86) mm Hg and (128.09±7.56) mm Hg respectively,which were significantly increased(P<0.05);(2) HF mainly caused the hyperplasia of vascular wall middle layer smooth muscle.The a-SMA expression results in the HF group was (0.006 3 ±0.000 21),which in the control group was (0.004 6 ± 0.000 31),the difference was statistically significant(P<0.05),moreover which promoted the elastic fibers increase;while HNa mainly stimulated the elastic fibers to thicken and extracellular matrix deposition,the fibronectin expression was 0.002 6 ± 0.000 2 in the HNa group and (0.004 7±0.000 2)in the HF group,compared with(0.001 3±0.000 1)in the normal group,which were significantly increased(P<0.001);(3) the blood pressure was (106.04±9.59) mm Hg in the HFLNa group,(103.99±7.12) mm Hg in the HFE group,compared with(133.94±5.86) mm Hg in the HF group,showing that the blood pressure in the HFLNa group and HFE group was significantly decreased compared with the HF group (P<0.05);moreover the vascular remodeling in the HFLNa group(0.006 8±0.000 2) and HFE group (0.004 2±0.000 4) was improved,and compared with the HF group(0.006 3±0.000 2),α-SMA expression was significantly decreased (P<0.05).Conclusion Low salt diet can effectively improve vascular remodeling induced by HEF.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of long non-coding RNA(lncRNA) RP11-770J1.3 and transmembrane protein 25 (TMEM25) on paclitaxel resistance in human breast cancer MCF-7/PR cell line.</p><p><b>METHODS</b>The expression of lncRNA RP11-770J1.3 and TMEM25 in human breast cancer MCF-7(paclitaxel sensitive) and MCF-7/PR(paclitaxel resistant) cells were detected by quantitative RT-PCR. The synthetic interfering fragments of lncRNA RP11-770J1.3 and TMEM25 were transfected into MCF-7/PR cells. Sulforhodamine B assay was used to detect the sensitivity of MCF-7/PR cells to paclitaxel after interference of lncRNA RP11-770J1.3 and TMEM25. The expression of multidrug-resistance genes and proteins were detected by qRT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>lncRNA RP11-770J1.3 and TMEM25 were highly expressed in MCF-7/PR cells, and were significantly down-regulated after transfection of synthetic interfering fragments. Down-regulation of lncRNA RP11-770J1.3 and TMEM25 enhanced the sensitivity of MCF-7/PR cells to paclitaxel, and inhibited the expression of MRP, BCRP and MDR1/P-gp (all<0.05). Such effects were more significant when lncRNA RP11-770J1.3 and TMEM25 were both down-regulated (all<0.05).</p><p><b>CONCLUSIONS</b>lncRNA RP11-770J1.3 and TMEM25 are highly expressed in MCF-7/PR cells, and the down-regulation of lncRNA RP11-770J1.3 and TMEM25 can enhance paclitaxel sensitivity in MCF-7/PR cells.</p>
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of CXC chemokine receptor 4 (CXCR4) on cell cycle of breast cancer and its molecular mechanisms.</p><p><b>METHODS</b>The expression of CXCR4 and S phase kinase associated protein 2 (Skp2) was detected by real-time fluorescence quantitative PCR (fqRT-PCR) and Western blot in breast cancer cells. The expression of signal proteins and the downstream genes of Skp2 was detected by Western blot. The effect of CXCR4, PI3K/Akt pathway inhibitor LY294002 and ERK pathway inhibitor U0126 on cell cycle of breast cancer was detected by propidium iodide staining.</p><p><b>RESULTS</b>Skp2 was significantly down-regulated in CXCR4-downregulated cells and up-regulated in CXCR4-upregulated cells. CXCR4 also regulated the expression of Skp2 and other downstream genes by signaling protein. The proportion of cells in G/Gphase increased and that in S phase declined in CXCR4-downregulated cell, and the effect was more significant when combined with the use of LY294002 or U0126.</p><p><b>CONCLUSIONS</b>CXCR4 can affect cell cycle and inhibit the proliferation of breast cancer cells by regulating Skp2 gene expression through PI3K/Akt and ERK signaling pathway.</p>
ABSTRACT
Objective To explore the relationship between angiogenin-1/2 (Ang-1/2) and clinical parameters of idiopathic pulmonary fibrosis (IPF), and to assess the value of Ang-1/2 in predicting the prognosis of patients with IPF.Methods A retrospective analysis was conducted. Ninety-one patients diagnosed as IPF by high resolution CT (HRCT) and lung biopsy admitted to Daqing Oil Field General Hospitalfrom March 2014 to January 2015 were enrolled. The general data, serum parameters and pulmonary function parameters of all patients were collected. After treatment, all of the 91 patients were followed-up to 2 years. The patients were divided into favorable prognosis group and unfavorable prognosis group according to follow-up results. The differences in all parameters between the two groups werecompared. The relationship between Ang-1, Ang-2 and lung function parameters was analyzed by Pearson correlation analysis. Cox proportional hazard regression model was used to evaluate the effect of clinical parameters on the prognosis of patients with IPF. The effect of Ang-2 in predicting prognosis of patients with IPF was analyzed by receiver operating characteristic (ROC) curve.Results During the 2-year follow-up period, 30 of 91 patients showed a favorable prognosis, and 55 showed an unfavorable prognosis with a poor prognosis rate of 64.71%, and 6 patients withdrew from the study due to loss of follow-up and death. Compared with the favorable prognosis group, Ang-2 level in the unfavorable prognosis group was significantly increased (μg/L: 2.88±1.63 vs. 1.89±1.22,t = 2.909,P= 0.005), but Ang-1 only showed a slight increase (μg/L: 28.70±14.26 vs. 25.62±11.95,t = 1.005,P = 0.318). The results of Pearson correlation analysis showed that Ang-2 level was negatively correlated with forced expiratory volume in 1 second (FVC1) and the percentage of carbon monoxide diffusing capacity accounting for the expected value (DLCO%;r value was -0.227 and -0.206, andP value was 0.147 and 0.253, respectively), but no significant correlation between the level of Ang-1 and FVC1 as well as DLCO% was found (r value was -0.153 and -0.121, andP value was 0.147 and 0.253, respectively). Cox proportional hazard regression model analysis showed that the prognosis of patients with IPF was significantly affected by smoking time and Ang-2 (bothP 0.05). Prognostic analysis showed that the area under ROC curve (AUC) of Ang-2 for predicting prognosis of patients with IPF was 0.692, and the best diagnostic point was 0.35μg/L, the sensitivity was 61.8%, the specificity was 73.3%, the positive predictive value was 69.8%, and the negative predictive value was 65.7% which indicated that Ang-2 could predict the prognosis of patients with IPF.Conclusion Ang-2 could assess the prognosis of patients with IPF, which is expected to be used as an indicator of predicting the prognosis of patients with IPF.
ABSTRACT
Objective To evaluate the correlations of emphysema and airway wall thickness to chronic obstructive pulmonary disease(COPD) of airflow limitation by quantitative CT.Methods 40 COPD patients and other 40 normal controls underwent pulmonary function tests and following MSCT exams with inspiration.The square root of wall area of an airway with an internal area of 8 mm2 (Ai8) and the percentage of low attenuation volume(LAV%) of the whole lung and each lobes at the threshold of-950 HU were measured by a software of Thoracic VCAR.The Ai8 between the observation group and the control one was compared using SPSS2.2.The contributions of LAV% and Ai8 to predictions of FEV1/FVC and FEV1% were also evaluated.Results There was a significantly statistical difference in the Ai8 between the observation group and the control one.There were correlations between airflow limitation markers and all of LAV% as well as Ai8 (P<0.05 for all standardized coefficients).Only the Ai8 of right inferior lobar made a significant contribution to airflow limitation in the whole lung bronchus, and the LAV% of each lobes made a stronger contribution to airflow limitation than the Ai8 of right inferior lobe.Conclusion There is a significantly statistical difference in the Ai8 between the observation group and the control one.The LAV% may make a greater contribution to airflow limitation than Ai8 in COPD group.The influential factors of airflow limitation in order were LAV%, Ai8 of right inferior lobe and Ai8 of the other lobes.
ABSTRACT
Objective To evaluate the value of spectral CT imaging for the differential diagnosis of squamous cell carcinoma (SQCC) and adenocarcinoma (ADC) of the esophagogastric junction. Methods Forty-five patients with a mass in the esophagogastric junction proved by pathology underwent enhanced scan with spectral CT, including 20 cases of SQCC and 25 cases of ADC. Iodine concentration (IC) , water concentration (WC) , effective atomic number (Eff-Z) and spectral curve slope (λHU) of arterial phase (AP) and venous phase (VP) in the ROI of the mass were measured with gemstone spectral imaging post-processing software. The independent samples t test was used to compare the quantitative parameters above between two groups on the premise of satisfying normal distribution. ROC curves were drawn for the parameters which showed statistical differences and area under the curve (AUC) was used to measure and compare their respective differential diagnostic performance as well as the best threshold value. Results In AP,the average IC, Eff-Z, andλHU of ADC were (1.75±0.40) mg/ml, 8.65±0.22, and 3.33±0.74, respectively. The corresponding parameters of SQCC were (1.40 ± 0.35) mg/ml, 8.50 ± 0.20, and 2.71 ± 0.66, respectively. These parameters of ADC were significantly higher than that of SQCC (t=-2.833,-2.879,-2.678;P<0.05) . In VP, the average IC, Eff-Z, and λHU of ADC were (2.17 ± 0.23) mg/ml, 8.87 ± 0.11, and 4.10 ± 0.44, respectively. The corresponding parameters of SQCC were (1.67 ± 0.20) mg/ml, 8.60 ± 0.11, and 3.19 ± 0.41, respectively. The difference between ADC and SQCC was statistically significant (t=-6.963,-7.218,-6.521;P<0.05). For the average WC, No difference between the two groups in AP and VP was found. ROC curve analysis showed that IC, Eff-Z, andλHU in VP had better differential diagnostic performances than IC, Eff-Z, and λHU in AP, especially Eff-Z in VP. The AUC for it was 0.97. Using 8.72 as a threshold value, the sensitivity and specificity for diagnosis were 88.9% and 94.7% , respectively. Conclusion Multi-parameters quantitative analysis with spectral CT could be useful in the differential diagnosis of SQCC and ADC of the esophagogastric junction.
ABSTRACT
BACKGROUND:Numerous diseases like cardiac hypertrophy and intervertebral disc degeneration are known to be implicated in the changes of mechanical stress acting on surrounding tissues or cells, and autophagy contributes to the pathogenesis of these diseases. OBJECTIVE:To review the effects of mechanical factors on autophagy in different tissues and the underlying molecular mechanisms, thereby providing references for the research of autophagy and the prevention and treatment of related diseases. METHODS:A search of Web of Science and PubMed databases was performed for the literatures addressing the effects of mechanical factors on autophagy using the English keywords ofautophagy, mechanicaland the articles were summarized systematically. Finally, 52 literatures were enrolled according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:Mechanical factors make great effects on autophagy of various cells, such as myocardial cells, endothelial cells, chondrocytes and skeletal muscle cells. Autophagy is a self-protective reaction, and the mechanical stress of physiological conditions induces autophagy to maintain cellhomeostasis, normal function and survival. The mechanism of autophagy induced by mechanical stress may involve PI3K-AKT-mTOR, oxygen free radical, AKT-FoxO and other pathways, and the definite mechanism needs to be further studied.