E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a mo...E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.展开更多
Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeut...Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.展开更多
BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC...BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.展开更多
In the new period, the physical education in colleges and universities is of greater and greater significance for the enhancement of students' learning efficiency. In this paper, the current situation of the current ...In the new period, the physical education in colleges and universities is of greater and greater significance for the enhancement of students' learning efficiency. In this paper, the current situation of the current physical education is analyzed, and also related suggestions on the optimization of the P.E. course teaching plan are proposed.展开更多
Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic ac...Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.展开更多
Objective: This study aimed to investigate the anti-inflammatory and analgesic mechanisms of a breast lump resolution detergent in a rat model of breast hyperplasia. Methods: A rat model of breast hyperplasia was esta...Objective: This study aimed to investigate the anti-inflammatory and analgesic mechanisms of a breast lump resolution detergent in a rat model of breast hyperplasia. Methods: A rat model of breast hyperplasia was established using injections of estradiol benzoate combined with progesterone. The effects of the breast lump resolution detergent on nipple height and diameter in the rat model were observed, along with its impact on serum levels of estradiol (E2), prolactin (PRL), and progesterone (P). Additionally, the study examined the morphological changes in breast tissue. The impact of the breast nodule detergent on blood rheology parameters was also observed. Furthermore, the anti-inflammatory effect of the breast nodule detergent was assessed using the cotton ball granuloma experiment, and the analgesic effect was observed using the writhing test. Results: The breast lump resolution detergent reduced nipple height and diameter in the rat model, decreased serum levels of E2, PRL, and P, and alleviated pathological changes in breast tissue. It also lowered hemorheological parameters including whole blood high, medium, and low shear viscosity, plasma viscosity, red blood cell hematocrit, red blood cell aggregation index, red blood cell deformability index, red blood cell electrophoresis time, and erythrocyte sedimentation rate in the acute “blood stasis” rat model. The detergent reduced the weight of cotton ball granulomas in mice and decreased the number of writhing episodes caused by acetic acid. Conclusion: The breast lump resolution detergent demonstrates favorable therapeutic effects in treating breast hyperplasia, promoting blood circulation and removing blood stasis, exerting anti-inflammatory properties, and providing analgesic effects. The downregulation of serum E2 and PRL levels and the upregulation of P levels may be critical mechanisms underlying its efficacy.展开更多
The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theor...The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theory which comes towards the end. Various general considerations as well as specific examples are given to illustrate and support our arguments. These examples range from the practical aspect to almost esoteric considerations but at the end, everything converges towards a unity of theory and computation presented in the form of modern fractal logic and transfinite quantum field theory in a Cantorian spacetime. It is true that all our examples are taken from physics but our discussion is applicable in equal measure to a much wider aspect of life.展开更多
The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accu...The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell’s fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ‘‘Letter to the Editor’’, we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.展开更多
Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm...Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm﹣1. The band due to C-H band and called hydrocarbon band was found only in paralytic and Alzheimer diseased along with normal healthy controls. Carbide band (C=C) is found only in Duchenne muscular dystrophy, paralytic and Alzheimer’s disease patients. Amide I was intact in all disorders with normal persons. Peroxide band (O-O) was found in all the cases of study. Amide IV band was found in paralytic, muscular dystrophy, Alzheimer’s diseases and normal controls. The amide V band was found in Alzheimer’s diseases only. The appearance or disappearance of the bands is a good sign to understand the mechanisms at the molecular level. FTIR spectroscopy may help in the diagnosis of the disease at the early stage of the onset. This spectroscopy can be used nicely for the study of hair, vaginal fluid, nails, urine, mucus, semen, synovial fluid, blood, hemoproteins, skin, and tears for human beings. We can also use it to understand the effect of adulteration on food and paint technology. FTIR is an indicator to explore the changes occurring at molecular level.展开更多
AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subject...AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.展开更多
AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the ...AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.展开更多
AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CY- P4502E1), environment risk factors with esophageal cancer (EC...AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CY- P4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China. METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 populationor hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis. RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502EIC1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502EIC1/ C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone. CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.展开更多
文摘E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.
文摘Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related sepsis.The research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and prevention.Methods:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related genes.Gene interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking potential.Techniques such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and MMP9.Results:The study identified 2,006 differentially expressed genes and 616 miRNAs.Key genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive state.Licorice glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating diabetes.The constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic cells.Conclusion:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes pathophysiology.Licorice glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER stress.The study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific understanding.Our study has limitations.It focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical trials.Despite strong in vitro findings,in vivo studies are needed to confirm licorice glycoside E’s therapeutic potential and understand the microRNA-149-5p-MMP9 dynamics in real conditions.
文摘BACKGROUND MicroRNAs(miRNAs)regulate gene expression and play a critical role in cancer physiology.However,there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer(GC).AIM To investigate the role and molecular mechanism of miRNA-145-5p(miR145-5p)in the progression of GC.METHODS Real-time polymerase chain reaction(RT-PCR)was used to detect miRNA expression in human GC tissues and cells.The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays,respectively.Cell proliferation was measured using cell counting kit-8 and colony formation assays,and apoptosis was evaluated using flow cytometry.Expression of the epithelial-mesenchymal transition(EMT)-associated protein was determined by Western blot.Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system.Serpin family E member 1(SERPINE1)expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining.The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis.The association between SERPINE1 and GC progression was also tested.A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p.The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice.RESULTS GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA.Overexpression of miR-145-5p was associated with decreased GC cell proliferation,invasion,migration,and EMT,and these effects were reversed by forcing SERPINE1 expression.Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression.Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2(ERK1/2).CONCLUSION This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC.MiR-145-5p was found to affect GC cell proliferation,migration,and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.
文摘In the new period, the physical education in colleges and universities is of greater and greater significance for the enhancement of students' learning efficiency. In this paper, the current situation of the current physical education is analyzed, and also related suggestions on the optimization of the P.E. course teaching plan are proposed.
基金financially supported by National Natural Science Foundation of China(81700524)Natural Science Foundation of Fujian Province(2022J01866)from Fujian Provincial Department of Science and Technology+1 种基金Key Project of Fujian University of Traditional Chinese Medicine(X2021019)Collaborative Innovation and Platform Establishment Project of Department of Science and Technology of Guangdong Province(2019A050520003)。
文摘Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.
文摘Objective: This study aimed to investigate the anti-inflammatory and analgesic mechanisms of a breast lump resolution detergent in a rat model of breast hyperplasia. Methods: A rat model of breast hyperplasia was established using injections of estradiol benzoate combined with progesterone. The effects of the breast lump resolution detergent on nipple height and diameter in the rat model were observed, along with its impact on serum levels of estradiol (E2), prolactin (PRL), and progesterone (P). Additionally, the study examined the morphological changes in breast tissue. The impact of the breast nodule detergent on blood rheology parameters was also observed. Furthermore, the anti-inflammatory effect of the breast nodule detergent was assessed using the cotton ball granuloma experiment, and the analgesic effect was observed using the writhing test. Results: The breast lump resolution detergent reduced nipple height and diameter in the rat model, decreased serum levels of E2, PRL, and P, and alleviated pathological changes in breast tissue. It also lowered hemorheological parameters including whole blood high, medium, and low shear viscosity, plasma viscosity, red blood cell hematocrit, red blood cell aggregation index, red blood cell deformability index, red blood cell electrophoresis time, and erythrocyte sedimentation rate in the acute “blood stasis” rat model. The detergent reduced the weight of cotton ball granulomas in mice and decreased the number of writhing episodes caused by acetic acid. Conclusion: The breast lump resolution detergent demonstrates favorable therapeutic effects in treating breast hyperplasia, promoting blood circulation and removing blood stasis, exerting anti-inflammatory properties, and providing analgesic effects. The downregulation of serum E2 and PRL levels and the upregulation of P levels may be critical mechanisms underlying its efficacy.
文摘The present paper is basically written as a non-apologetic strong defence of the thesis that computation is part and parcel of a physical theory and by no means a mere numerical evaluation of the prediction of a theory which comes towards the end. Various general considerations as well as specific examples are given to illustrate and support our arguments. These examples range from the practical aspect to almost esoteric considerations but at the end, everything converges towards a unity of theory and computation presented in the form of modern fractal logic and transfinite quantum field theory in a Cantorian spacetime. It is true that all our examples are taken from physics but our discussion is applicable in equal measure to a much wider aspect of life.
文摘The E2F proteins comprise a family of 8 members that function as transcription factors. They are key targets of the retinoblastoma protein (RB) and were initially divided into groups of activators and repressors. Accumulating data suggest that there is no specific role for each individual E2F member. Instead, each E2F can exert a variety of cellular effects, some of which represent opposing ones. For instance, specific E2Fs can activate transcription and repression, promote or hamper cell proliferation, augment or inhibit apoptosis, all being dependent on the cellular context. This complexity reflects the importance that these transcription factors have on a cell’s fate. Thus, delineating the specific role for each E2F member in specific malignancies, although not easy, is a challenging and continuously pursued task, especially in view of potential E2F targeted therapies. Therefore, several reviews are continuously trying to evaluate available data on E2F status in various malignancies. Such reviews have attempted to reach a consensus, often in the simplistic form of oncogenes or tumor suppressor genes for the E2Fs. However they frequently miss spatial and temporal alterations of these factors during tumor development, which should also be considered in conjunction with the status of the regulatory networks that these factors participate in. In the current ‘‘Letter to the Editor’’, we comment on the flaws, misinterpretations and omissions in one such review article published recently in the World Journal of Gastroenterology regarding the role of E2Fs in digestive system malignancies.
文摘Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm﹣1. The band due to C-H band and called hydrocarbon band was found only in paralytic and Alzheimer diseased along with normal healthy controls. Carbide band (C=C) is found only in Duchenne muscular dystrophy, paralytic and Alzheimer’s disease patients. Amide I was intact in all disorders with normal persons. Peroxide band (O-O) was found in all the cases of study. Amide IV band was found in paralytic, muscular dystrophy, Alzheimer’s diseases and normal controls. The amide V band was found in Alzheimer’s diseases only. The appearance or disappearance of the bands is a good sign to understand the mechanisms at the molecular level. FTIR spectroscopy may help in the diagnosis of the disease at the early stage of the onset. This spectroscopy can be used nicely for the study of hair, vaginal fluid, nails, urine, mucus, semen, synovial fluid, blood, hemoproteins, skin, and tears for human beings. We can also use it to understand the effect of adulteration on food and paint technology. FTIR is an indicator to explore the changes occurring at molecular level.
基金Supported by Theodor Bilharz Research Institute(Grant# 74D) in collaboration with the American University of Cairo
文摘AIM:To investigate cell cycle proteins in chronic hepatitis C virus infection in order to analyze their role in the process of hepatocyte transformation and to characterize their prognostic properties. METHODS:Subjects of the current study included 50 cases of chronic hepatitis C(CHC) without cirrhosis,30 cases of CHC with liver cirrhosis(LC) ,and 30 cases of hepatitis C-related hepatocellular carcinoma(HCC) admitted to the Department of Hepato-Gastroenterology,Theodor Bilharz Research Institute(TBRI) ,Giza,Egypt.Fifteen wedge liver biopsies,taken during laparoscopic cholecystectomy,were also included as normal controls.Laboratory investigations including urine and stool analysis,liver function tests and prothrombin concentration;serologic markers for viral hepatitis and ultrasonography were done for all cases of the study together with immunohistochemical analysis using primary antibodies against Cyclin D1,Cyclin E,p21,p27 and Rb/p105 proteins. RESULTS:Normal wedge liver biopsies didn't express Cyclin E or Rb/p105 immunostaining but show positive staining for Cyclin D1,p21 and p27.Cyclin D1 expressed nuclear staining that was sequentially increased from CHC to LC(P<0.01) to HCC(P<0.001) cases;meanwhile,Cyclin E revealed nuclear positivity only in the case of HCCs patients that was directly correlated to Rb/p105 immuno-reactivity.The expression of p21 and p27 was significantly increased in CHC and LC cases compared to normal controls and HCCs with no significant difference between well-and poorlydifferentiated tumors.p21 showed only a nuclear pattern of staining,while,p27 presented with either cytoplasmic and/or nuclear reactivity in all studied cases.Correlation analysis revealed a direct relation between Cyclin D1 and p21 in CHC cases(P<0.001) ,between Cyclin D1 and Cyclin E in HCCs(P<0.01);however,an inverserelationship was detected between Cyclin D1 and p21 or p27(P<0.001) and between p21 and Rb/p105(P<0.05) in HCCs. CONCLUSION:Upregulation of Cyclin D1 in CHC plays a vital role in the development and differentiation of HCC;while,Cyclin E may be a useful marker for monitoring tumor behavior.p21 and p27 can be used as predictive markers for HCC.Furthermore,higher expression of Rb/p105 as well as inverse relation with p21 and histologic grades suggests its important role in hepatic carcinogenesis.
文摘AIM:To investigate the correlation of hyperlipemia(HL) and acute cerebral ischemia/reperfusion(I/R) injury on liver damage and its mechanism.METHODS:Rats were divided into 4 groups:control,HL,I/R and HL+I/R.After the induction of HL via a high-fat diet for 18 wk,middle cerebral artery occlusion was followed by 24 h of reperfusion to capture I/R.Serum alanine transaminase(ALT) and aspartate aminotransferase(AST) were analyzed as part of liver function tests and liver damage was further assessed by histological examination.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling(TUNEL) assay.The expression of genes related to apoptosis(caspase-3,bcl-2) was assayed by immunohistochemistry and Western blotting.Serum tumor necrosis factor-(TNF-),interleukin-1(IL-1) and liver mitochondrial superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA) and Ca 2+ levels were measured to determine inflammatory and oxidative/antioxidative status respectively.Microsomal hydroxylase activity of the cytochrome P450 2E1(CYP2E1)-containing enzyme was measured with aniline as the substrate,and CYP2E1 expression in the liver tissue and microsome was determined by immunohistochemistry and Western blotting respectively.RESULTS:HL alone induced by high-fat diet for 18 wk resulted in liver damage,indicated by histopathological analysis,and a considerable increase in serum ALT(25.13 ± 16.90 vs 9.56 ± 1.99,P < 0.01) and AST levels(18.01 ± 10.00 vs 11.33 ± 4.17,P < 0.05) compared with control.Moreover,HL alone induced hepatocyte apoptosis,which was determined by increased TUNEL-positive cells(4.47 ± 0.45 vs 1.5 ± 0.22,P < 0.01),higher caspase-3 and lower bcl-2 expression.Interestingly,compared with those in control,HL or I/R groups,massive increases of serum ALT(93.62 ± 24.00 vs 9.56 ± 1.99,25.13 ± 16.90 or 12.93 ± 6.14,P < 0.01) and AST(82.32 ± 26.92 vs 11.33 ± 4.17,18.01 ± 10.00 or 14.00 ± 6.19,P < 0.01) levels in HL+I/R group were observed suggesting severe liver damage,which was confirmed by liver histology.In addition,HL combined with I/R also caused significantly increased hepatocyte apoptosis,as evidenced by increased TUNEL-positive cells(6.20 ± 0.29 vs 1.5 ± 0.22,4.47 ± 0.45 or 1.97 ± 0.47,P < 0.01),elevated expression of caspase-3 and lower expression of bcl-2.Furthermore,when compared to HL or I/R alone,HL plus I/R enhanced serum TNF-,IL-1,liver mitochondrial MDA and Ca 2+ levels,suppressed SOD and GSH-Px in liver mitochondria,and markedly up-regulated the activity(11.76 ± 2.36 vs 4.77 ± 2.31 or 3.11 ± 1.35,P < 0.01) and expression(3.24 ± 0.38 vs 1.98 ± 0.88 or 1.72 ± 0.58,P < 0.01) of CYP2E1 in liver.CONCLUSION:The coexistence of HL and acute cerebral I/R induces severe liver damage,suggesting that cerebral ischemic stroke would exaggerate the damage of liver caused by HL.This effect is possibly due to en-hanced CYP2E1 induction which further promotes oxidative damage,inflammation and hepatocyte apoptosis.
基金Supported by The National Natural Science Foundation of China, No. 30660161Prophase Basic Research Project of Ministry of Science and Technology of China, No. 2005CCA03700, No. 2007CB516804+1 种基金Science and Technology Research Project of Ministry of Education of China, No. 206167Laboratory of Endemic and Ethnic Diseases Program of Xinjiang, No. 200416
文摘AIM: To evaluate the association and interaction of genetic polymorphisms in methylenetetrahydrofolate reductase (MTHER) and cytochrome P4502E1 (CY- P4502E1), environment risk factors with esophageal cancer (EC) in Kazakh, a high EC incidence area of Xinjiang Uygur Autonomous Region, China. METHODS: A 1:2 matched case-control study was conducted with 120 cases of EC and 240 populationor hospital-based controls. The controls were matched for sex, nationality, area of residence and age within a 5-year difference. MTHER and CYP4502E1 genotypes were identified by PCR-based restriction fragment length polymorphism (RFLP). A conditional logistic regression model was established to identify risk factors. The strata method was adopted in interaction analysis. RESULTS: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) were found to be the risk factors for EC. Individuals with the MTHFR677 (C/T + T/T) genotype had a 2.62-fold (95% CI: 1.61-4.28) risk of developing EC compared with those who carried the C/C genotype. Individuals with the CYP4502EIC1/C1 genotype had a 3.00-fold (95% CI: 1.82-4.96) risk compared with those who carried the CYP4502E1 (C1/C2 + C2/C2) genotype. Gene-environment interaction analysis showed that MTHFR677 gene polymorphism was correlated with consumption of green vegetables and fresh fruit, while CYP4502E1 C1/C1 was correlated with alcohol drinking and unsafe drinking water. MTHFR and CYP4502E1 analysis of gene-gene interaction showed that individuals with the MTHFR677 (C/T + T/T) and CYP4502EIC1/ C1 genotypes had a 7.41-fold (95% CI: 3.60-15.25) risk of developing EC compared with those who carried the MTHFR677C/C and CYP4502E1 RsaI C1/C2 + C2/C2 genes, and the interaction rate was higher than that of the two factors alone. CONCLUSION: Low consumption of green vegetables and fresh fruits, alcohol drinking, and unsafe water (shallow well, or river) and polymorphisms in MTHFR and CYP4502E1 genes are important risk factors for EC. There is a synergistic interaction among polymorphisms in MTHFR and CYP4502E1 genes and environment factors. MTHFR and CYP4502E1 genes can be used as biomarkers for prevention of EC in Kazakh, Xinjiang Uygur Autonomous Region, China.