AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS: This prospective study was conducted on...AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-na?ve chronic hepatitis C(CH)(n = 30), post-hepatitis C compensated cirrhosis(LC)(n = 30) and treatment-naive HCC(n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miR NA expression by RT-PCR.RESULTS: There was a significant fold change in serum mi RNA expression in the different patient groups when compared to normal controls; mi R-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, mi R-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group(P = 0.01). Comparing fold changes in miR NAs in HCC group vs non HCC group(CH and Cirrhosis), there was non-significant fold elevation in miR-122(P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC(P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.展开更多
AIM: To investigate the association of the functional monocyte chemotactic protein-1(MCP-1) promoter polymorphism(A-2518G) with spontaneous bacterial peritonitis(SBP).METHODS: Fifty patients with post-hepatitis C live...AIM: To investigate the association of the functional monocyte chemotactic protein-1(MCP-1) promoter polymorphism(A-2518G) with spontaneous bacterial peritonitis(SBP).METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group Ⅰ included 25 patients with SBP and group Ⅱ included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin(IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups Ⅰ and Ⅱ(P = 0.001 and 0.02 respectively). Group Ⅰ was associated with a significantly higher frequency of AG genotype [control 8(40%) vs SBP 19(76.0%), P < 0.001], and group Ⅱ was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1(5%) vs cirrhotic 16(64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups(Ⅰ and Ⅱ) [control 10(25%) vs SBP 27(54%), P < 0.001 and vs cirrhotic 37(74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group Ⅰ than in group Ⅱ. Group Ⅰ showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.展开更多
AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represe...AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P < 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P < 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P < 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P < 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P < 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P <0.01,P < 0.001 and P < 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P < 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P < 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P < 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.展开更多
Gastric cancer(GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging Ⅱ-Ⅳ. Unfortunately, while the majority of GC patient...Gastric cancer(GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging Ⅱ-Ⅳ. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.展开更多
BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat mode...BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.展开更多
<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for in...<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.展开更多
AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson's disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propa...AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson's disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1(89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF(3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA(874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH(1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin(1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin(293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.展开更多
The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such ...The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such as this one.Stem cells have the capacity for self-renewal and differentiation into certain cell lineages.The present study was aimed to find out the most beneficial route of bone marrow-derived mesenchymal stem cells(BMSCs)administration for the attenuation of experimentally induced HIE in neonatal rats.Sixty neonatal rats were divided randomly into four groups.Group 1:control group.Group 2:rats were exposed to bilateral ligation of cephalic arteries.Group 3:rats were exposed to bilateral ligation of cephalic arteries and then underwent intravenous(IV)BMSC injection.Group 4:rats were exposed to bilateral ligation of cephalic arteries and then underwent intracerebroventricular(ICV)BMSC injection.The animals were evaluated by(a)neurobehavioral tests;(b)histopathology,i.e.,histological and immuno-histochemical studies;and(3)gene expression studies.The BMSC treated groups(3 and 4)showed improvement in neurobehavioral tests,histopathological studies,and gene expression,as compared to non-injected lesioned rats(Group 2)with better improvement in Group 4(ICV injections)than in Group 3(IV injections).展开更多
The incidence of bladder cancer(BC) continues to rise with high recurrence and mortality rate, especially in the past three decades. The development of accurate and successful BC treatment relies mainly on early diagn...The incidence of bladder cancer(BC) continues to rise with high recurrence and mortality rate, especially in the past three decades. The development of accurate and successful BC treatment relies mainly on early diagnosis. BC is a heterogeneous disease reflected by the presence of many potential biomarkers associated with different disease phenotypes. Nowadays, cystoscopy and urinary cytology are considered the gold standard diagnostic tools for BC. There are many limitations to cystoscopy including being invasive, labor-intensive and carcinoma in situ of the bladder may easily be missed. Urinary cytology is still a noninvasive technique with high accuracy in high-grade BC with a median sensitivity of 35%. Furthermore, the need for a sensitive, specific, non invasive, easily accessible BC biomarker is a major clinical need. The field of urinary BC biomarkers discovery is still a rapidly evolving discipline in which more recent technologies are evaluated and often optimized if they are not clinically significant to the urologists. Most of the current strategies for BC urinary biomarker detection depend on integration of information gleaned from the fields of genomics, transcriptomics, proteomics, epigenetics, metabolomics and bionanotechnology. Effort is currently being made to identify the most potentially beneficial urinary biomarkers. The purpose of this review is to summarize and explore the efficacy of gathering the information revealed from the cooperation of different omic strategies that paves the way towards various urinary markers discovery for screening, diagnosis and prognosis of human BC.展开更多
Current estimates indicate that the hepatitis C(HCV)is the leading cause of mortality around the world,with infection rates steadily increasing in Egypt.The dual therapy for this silent epidemic with pegylated-interfe...Current estimates indicate that the hepatitis C(HCV)is the leading cause of mortality around the world,with infection rates steadily increasing in Egypt.The dual therapy for this silent epidemic with pegylated-interferon-a2b/ribavirin has markedly improved the success rates in genotype-4 patients.It was reported that apoptosis plays a vital mechanistic role in limiting viral replication.P53,a key regulator of apoptosis,induces CD95 gene expression and subsequently initiates apoptotic cascade to be activated.The current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment response.Three groups of 240 volunteers were enrolled in this study;86 in sustained virological responders group,74 in non-responders group,and 80 in control group.All patients had HCV genotype-4a and were interferon treatment naı¨ve.Quantizations of HCV-RNA by qRT-PCR and histological scores were performed for all patients.In addition,genotyping of HCV-RNA,P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all subjects.It was resulted that P53 Pro/Pro homozygous genotype has high significant increase,while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with responders.Finally,it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness,while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection.In addition,low prolactin,high total testosterone,and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.展开更多
The study of circadian rhythm performance is prominent in chronic diseases, such as multiple sclerosis(MS). Circadian rhythm dysregulation has been observed in several neurodegenerative disorders, including MS, Alzhei...The study of circadian rhythm performance is prominent in chronic diseases, such as multiple sclerosis(MS). Circadian rhythm dysregulation has been observed in several neurodegenerative disorders, including MS, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease(Videnovic et al., 2014;Hedstr om et al.,2015). In addition, subjects who work in shifts have an increased risk of developing MS(Hedstr om et al., 2015). Furthermore, impaired sleep and alertness are common symptoms of MS and neurodegenerative disorders(Videnovic et al., 2014).展开更多
文摘AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus(HCV)-related hepatocellular carcinoma(HCC).METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-na?ve chronic hepatitis C(CH)(n = 30), post-hepatitis C compensated cirrhosis(LC)(n = 30) and treatment-naive HCC(n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miR NA expression by RT-PCR.RESULTS: There was a significant fold change in serum mi RNA expression in the different patient groups when compared to normal controls; mi R-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, mi R-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group(P = 0.01). Comparing fold changes in miR NAs in HCC group vs non HCC group(CH and Cirrhosis), there was non-significant fold elevation in miR-122(P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC(P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82. CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.
文摘AIM: To investigate the association of the functional monocyte chemotactic protein-1(MCP-1) promoter polymorphism(A-2518G) with spontaneous bacterial peritonitis(SBP).METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group Ⅰ included 25 patients with SBP and group Ⅱ included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin(IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups Ⅰ and Ⅱ(P = 0.001 and 0.02 respectively). Group Ⅰ was associated with a significantly higher frequency of AG genotype [control 8(40%) vs SBP 19(76.0%), P < 0.001], and group Ⅱ was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1(5%) vs cirrhotic 16(64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups(Ⅰ and Ⅱ) [control 10(25%) vs SBP 27(54%), P < 0.001 and vs cirrhotic 37(74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group Ⅰ than in group Ⅱ. Group Ⅰ showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.
文摘AIM To assess the levels of different immune modulators in patients with hepatocellular carcinoma(HCC),in relation to other hepatic diseases.METHODS Eighty-eight patients were included in the current study and represented patients with HCC(20),liver cirrhosis(28) and chronic hepatitis(CH;25),and normal controls(NC;15).Peripheral blood was isolated for immunophenotyping of active myeloid dendritic cells(m DCs;CD1 c and CD40),mature inactive myeloid cells(CD1 c and HLA),active plasmacytoid cells(p DCs;CD303 and CD40),mature inactive p DCs(CD30 and HLA),active natural killer(NK) cells(CD56 and CD161),active NK cells(CD56 and CD314) and inactive NK cells(CD56 and CD158) was done by flow cytometry.Serum levels of interleukin(IL)-2,IL-10,IL-12,IL-1β,interferon(IFN)-α,IFN-γ and tumor necrosis factor(TNF)-αR2 were assessed by ELISA.RESULTS Active m DCs(CD1 C+/CD40+) and inactive m DCs(CD1 c+/HLA+) were significantly decreased in HCC patients in relation to NC(P < 0.001).CD40+ expression on active p DCs was decreased in HCC patients(P < 0.001),and its level was not significantly changed among other groups.Inactive p DCs(CD303+/HLA+),inactive NKs(CD56+/CD158+) and active NKs(CD56+/CD161+) were not statistically changed among the four groups studied;however,the latter was increased in CH(P < 0.05).NKG2 D was statistically decreased in HCC,CH and cirrhosis(P < 0.001),and it was not expressed in 63%(12/20) of HCC patients.There was significant decrease of IL-2,IFN-α and IFN-γ(P < 0.001),and a significant increase in IL-10,IL-1β,and TNF-αR2(P <0.01,P < 0.001 and P < 0.001;respectively) in HCC patients.There was inverted correlation between IL-12 and IL-1β in HCC(r =-0.565,P < 0.01),with a strong correlation between p DCs(CD303+/CD40+) and NKs(CD56+/CD161+;r = 0.512,P < 0.05) as well as inactive m DCs(CD1 c+/HLA+) and inactive NK cells(CD56+/CD158+;r = 0.945,P < 0.001).CONCLUSION NKG2 D,CD40,IL-2 and IL-10 are important modulators in the development and progression of HCC.
文摘Gastric cancer(GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging Ⅱ-Ⅳ. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.
文摘BACKGROUND Diethylnitrosamine(DEN)induces hepatic neoplastic lesions over a prolonged period.AIM To investigate the promotive action of 2-acetylaminofluorene(2-AAF)when combined with DEN in order to develop a rat model for induction of precancerous lesion and investigate the molecular mechanism underlying the activity of 2-AAF.METHODS The pre-precancerous lesions were initiated by intraperitoneal injection of DEN for three weeks consecutively,followed by one intraperitoneal injection of 2-AAF at three different doses(100,200 and 300 mg/kg).Rats were separated into naïve,DEN,DEN+100 mg 2-AAF,DEN+200 mg 2-AAF,and DEN+300 mg 2-AAF groups.Rats were sacrificed after 10 wk and 16 wk.Liver functions,level of alpha-fetoprotein,glutathione S-transferase-P and proliferating cell nuclear antigen staining of liver tissues were performed.The mRNA level of RAB11A,BAX,p53,and Cyclin E and epigenetic regulation by long-noncoding RNA(lncRNA)RP11-513I15.6,miR-1262(microRNA),and miR-1298 were assessed in the sera and liver tissues of the rats.RESULTS 2-AAF administration significantly increased the percent area of the precancerous foci and cell proliferation along with a significant decrease in RAB11A,BAX,and p53 mRNA,and the increase in Cyclin E mRNA was associated with a marked decrease in lncRNA RP11-513I15.6 expression with a significant increase in both miR-1262 and miR-1298.CONCLUSION 2-AFF promoted hepatic precancerous lesions initiated through DEN by decreasing autophagy,apoptosis,and tumor suppression genes,along with increased cell proliferation,in a time-and dose-dependent manner.These actions were mediated under the epigenetic regulation of lncRNA RP11-513I15.6/miR-1262/miR-1298.
文摘<strong>Background:</strong> Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by <em>β</em>-cell dysfunction and resistance for insulin. Vitamin D is necessary for insulin secretion so it is a crucial factor in the development of T2DM. This study was done to investigate the association between serum 25-hydroxy Vitamin D [25(OH)3D], VDR (Vitamin D receptor) and VDBP (Vitamin D binding protein) with type 2 diabetic patients compared to control subjects.<strong> Subjects and Methods:</strong> This study carried out 110 female patients who were previously diagnosed with type 2 diabetes and 110 age, sex and weight matched as controls. All participants were subjected to full history taking, clinical examination and assessment of fasting blood glucose, HbA1c , lipid profile, 25-hydroxy Vitamin D [25(OH)3D], VDR and VDBP. <strong>Results:</strong> Results showed that the level of 25(OH)3D was significantly lower in diabetic group compared to controls and was significantly negatively correlated with glycated hemoglobin, serum total cholesterol and low density lipoprotein cholesterol in type 2 DM. Decreasing Vitamin D level was significantly associated with decreasing VDR. No significant association was found between Vit D and VDBP levels. <strong>Conclusions:</strong> Vitamin D deficiency is frequent in diabetic patients and associated with poor control and outcome. This suggests a role of Vitamin D in the pathogenesis and control of T2DM. Serum VDBP in diabetes may be independent to the level of 25(OH)3D and needs further studies.
文摘AIM: To explore the approaches exerted by mesenchymal stem cells(MSCs) to improve Parkinson's disease(PD) pathophysiology.METHODS: MSCs were harvested from bone marrowof femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group(1) was control, Groups(2) and(3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group(2) was left untreated, while Group(3) was treated with single intravenous dose of bone marrow derived MSCs(BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1(TGF-β1), monocyte chemoattractant protein-1(MCP-1) and brain derived neurotrophic factor(BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase(TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1(489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1(89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF(3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA(874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH(1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin(1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin(293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
文摘The neonatal hypoxic-ischemic encephalopathy(HIE)is an important cause of neurological morbidity and mortality in neonates.Cell therapy is considered a promising method for treating severe neurological disorders such as this one.Stem cells have the capacity for self-renewal and differentiation into certain cell lineages.The present study was aimed to find out the most beneficial route of bone marrow-derived mesenchymal stem cells(BMSCs)administration for the attenuation of experimentally induced HIE in neonatal rats.Sixty neonatal rats were divided randomly into four groups.Group 1:control group.Group 2:rats were exposed to bilateral ligation of cephalic arteries.Group 3:rats were exposed to bilateral ligation of cephalic arteries and then underwent intravenous(IV)BMSC injection.Group 4:rats were exposed to bilateral ligation of cephalic arteries and then underwent intracerebroventricular(ICV)BMSC injection.The animals were evaluated by(a)neurobehavioral tests;(b)histopathology,i.e.,histological and immuno-histochemical studies;and(3)gene expression studies.The BMSC treated groups(3 and 4)showed improvement in neurobehavioral tests,histopathological studies,and gene expression,as compared to non-injected lesioned rats(Group 2)with better improvement in Group 4(ICV injections)than in Group 3(IV injections).
文摘The incidence of bladder cancer(BC) continues to rise with high recurrence and mortality rate, especially in the past three decades. The development of accurate and successful BC treatment relies mainly on early diagnosis. BC is a heterogeneous disease reflected by the presence of many potential biomarkers associated with different disease phenotypes. Nowadays, cystoscopy and urinary cytology are considered the gold standard diagnostic tools for BC. There are many limitations to cystoscopy including being invasive, labor-intensive and carcinoma in situ of the bladder may easily be missed. Urinary cytology is still a noninvasive technique with high accuracy in high-grade BC with a median sensitivity of 35%. Furthermore, the need for a sensitive, specific, non invasive, easily accessible BC biomarker is a major clinical need. The field of urinary BC biomarkers discovery is still a rapidly evolving discipline in which more recent technologies are evaluated and often optimized if they are not clinically significant to the urologists. Most of the current strategies for BC urinary biomarker detection depend on integration of information gleaned from the fields of genomics, transcriptomics, proteomics, epigenetics, metabolomics and bionanotechnology. Effort is currently being made to identify the most potentially beneficial urinary biomarkers. The purpose of this review is to summarize and explore the efficacy of gathering the information revealed from the cooperation of different omic strategies that paves the way towards various urinary markers discovery for screening, diagnosis and prognosis of human BC.
基金This work was supported by Medical Research Division of the National Research Centre(NRC),Cairo,Egypt and the Egyptian Science and Technology Development Fund(STDF)[Grant number 1512 to Olfat G.Shaker].
文摘Current estimates indicate that the hepatitis C(HCV)is the leading cause of mortality around the world,with infection rates steadily increasing in Egypt.The dual therapy for this silent epidemic with pegylated-interferon-a2b/ribavirin has markedly improved the success rates in genotype-4 patients.It was reported that apoptosis plays a vital mechanistic role in limiting viral replication.P53,a key regulator of apoptosis,induces CD95 gene expression and subsequently initiates apoptotic cascade to be activated.The current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment response.Three groups of 240 volunteers were enrolled in this study;86 in sustained virological responders group,74 in non-responders group,and 80 in control group.All patients had HCV genotype-4a and were interferon treatment naı¨ve.Quantizations of HCV-RNA by qRT-PCR and histological scores were performed for all patients.In addition,genotyping of HCV-RNA,P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all subjects.It was resulted that P53 Pro/Pro homozygous genotype has high significant increase,while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with responders.Finally,it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness,while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a infection.In addition,low prolactin,high total testosterone,and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.
文摘The study of circadian rhythm performance is prominent in chronic diseases, such as multiple sclerosis(MS). Circadian rhythm dysregulation has been observed in several neurodegenerative disorders, including MS, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease(Videnovic et al., 2014;Hedstr om et al.,2015). In addition, subjects who work in shifts have an increased risk of developing MS(Hedstr om et al., 2015). Furthermore, impaired sleep and alertness are common symptoms of MS and neurodegenerative disorders(Videnovic et al., 2014).
