In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNC...In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.展开更多
Objective:To make evidence-based decisions based on broad mortality trends for Razavi Khorasan province,Iran.Methods:In order to determine the baseline number of deaths,we used univariate time series analyses for mont...Objective:To make evidence-based decisions based on broad mortality trends for Razavi Khorasan province,Iran.Methods:In order to determine the baseline number of deaths,we used univariate time series analyses for monthly data from the monthly vital statistics reports(From April 2015 to March 2022).For excess mortalities,these baselines were subtracted from reported deaths with a 95%prediction interval.To compare time and causes,a P-score was calculated.Results:From March 2020 to March 2022,there were 61949 registered deaths,and the estimated deaths with a 95%confidence interval(CI)were 43246.16(35718.28,50774.05).So,in 2020-2021 and 2021-2022,the death counts were 35.15%and 51.33%higher than projected.A total of 18666 cardiovascular diseases were reported and a total of 15704.46(12006.95,19401.96)was estimated.The P-score for this duration was 14.49%and 23.23%higher than expected.Infectious and parasitic diseases plus COVID-19 were 16633 and estimated to be 1044.87(456.77,1632.96).A total of 4420 diseases of the respiratory system were reported,and 4564.94 deaths were predicted(2277.43,6852.43).In the first year of the pandemic,the P-score dropped to-35.28%and in the second year,it jumped sharply to 22.38%.Conclusions:Excess mortality,along with cause-specific mortality,can be helpful for monitoring trends and developing public health policies at the local,national,and international levels.展开更多
Liver transplant(LT)outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbid...Liver transplant(LT)outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbidities,including complications of metabolic syndrome and de novo neoplasms,seem to play a key role in determining long-term outcomes in LT recipients.This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation.In particular,the reduction of drug toxicity,the use of tools to identify high-risk patients,and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.展开更多
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched Pub Med, Scopus...AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched Pub Med, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the Clinical Trials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes(recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof-bias. Between-study heterogeneity was assessed, and pooled risk ratio(RR) estimates with their 95% confidence intervals(95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat(NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas(fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20(95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance(fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.展开更多
Phage display is very strong technique in drug discovery and development. Phage display has many applications in improving the immunological studies. Development of monoclonal antibody, peptides, peptidomimetics and e...Phage display is very strong technique in drug discovery and development. Phage display has many applications in improving the immunological studies. Development of monoclonal antibody, peptides, peptidomimetics and epitope mapping are main application of phage display. Selection of monoclonal antibody or peptides that are displayed on the surface of the phages can be occurred through biopanning process. In biopanning process phage library is incubated with antigen and particular phages can be identified and isolated. Increasing the stringency in the biopanning rounds can be help to select phages with high affinity and specificity. Here, we describe an overview of phage display application with focusing on monoclonal antibody production and epitope mapping.展开更多
In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and progression.Within TME,cells from adaptive and innate immune system are one of the main...In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and progression.Within TME,cells from adaptive and innate immune system are one of the main abundant components.The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth.This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer,such as hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).Liver is well-known to be an important immunological organ with unique microenvironment.Here,in normal conditions,the rich immune-infiltrating cells cooperate with non-parenchymal cells,such as liver sinusoidal endothelial cells and Kupffer cells,favoring self-tolerance against gut antigens.The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells,in order to understand how this cross-talk promotes tumor growth.Deeper attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment.In this review,we will examine the key pathways underlying TME cell-cell communications,with deeper focus on the role of natural killer cells in primary liver tumors,such as HCC and iCCA,as new opportunities for immune-based therapeutic strategies.展开更多
Objective: To express human Vascular endothelial growth factor121(VEGF121) in insect cells. Methods: A gene construct containing VEGF was cloned in the p Fast Bac-HTA vector, followed by transformation in DH10 BAC. Th...Objective: To express human Vascular endothelial growth factor121(VEGF121) in insect cells. Methods: A gene construct containing VEGF was cloned in the p Fast Bac-HTA vector, followed by transformation in DH10 BAC. The recombinant bacmid was then extracted, and transfected into Sf9 insect cells. The transfected cells were harvested, and then VEGF expression was confirmed by Western blotting using specific antibodies. The tube formation assay was used for functional assessment of VEGF. Results: Our results showed that VEGF could be successfully expressed in the baculovirus system. Purified VEGF was able to stimulate in vitro tube formation of human endothelial cells. Conclusions: Results from this study demonstrated that the recombinantly-produced VEGF can be considered as a promising candidate for therapeutic purposes.展开更多
Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis ...Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.展开更多
Differential diagnosis of supraventricular tachycardia (SVT) and ventricular tachycardia (VT) is of paramount importance for appropriate patient management. Several diagnostic algorithms for discrimination of VT and S...Differential diagnosis of supraventricular tachycardia (SVT) and ventricular tachycardia (VT) is of paramount importance for appropriate patient management. Several diagnostic algorithms for discrimination of VT and SVT based on surface electrocardiogram (ECG) analysis have been proposed. Following established diagnosis of VT,a specific origination tachycardia site can be supposed according to QRS complex characteristics. This review aims to cover comprehensive and comparative description of the main VT diagnostic algorithms and to present ECG characteristics which permit to suggest the most common VT origination sites.展开更多
Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological h...Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological hallmark of many late-onset NDs called proteinopathies including Parkinson’s disease(PD),Alzheimer’s disease(AD),tauopathies,amyotrophic lateral sclerosis(ALS),and polyglutamine(polyQ)expansion diseases such as Huntington’s disease(HD)and various spinocerebellar ataxias(SCA)such as SCA3(Renna et al.,2010).Misfolded proteins can be generated by posttranslational conjugation(e.g.,hyperphosphorylated tau in AD),or endoproteolytic cleavage(e.g.,amyloidβpeptides)or genetic mutations in specific proteins(such as HTT in HD,α-synuclein in PD,PrPC in prion disease and SOD1 and TDP-43 in ALS)leading to the formation of oligomers.展开更多
Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment ...Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.展开更多
Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,t...Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.展开更多
AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional co...AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.展开更多
BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as ...BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different methods.On the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over time.AIM To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics.METHODS Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed.The diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were measured.The development of worrisome features was evaluated.RESULTS We evaluated exams of 98 patients across a 40.5-mo median follow-up time.Ten patients developed worrisome features.Cysts at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical significance.Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs.Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.展开更多
The antibiotic therapy has many problems, such as antibiotics resistance, hypersensitivity, direct toxicity, antibiotic-induced immunosuppresion and super-infections. This is highlighting the need for a new strategy f...The antibiotic therapy has many problems, such as antibiotics resistance, hypersensitivity, direct toxicity, antibiotic-induced immunosuppresion and super-infections. This is highlighting the need for a new strategy for non-antibiotic therapy through the use of novel immunomodulators as naturally released ones (Lactoferrin). The present study investigates the potential of bovine lactoferrin (bLf), isolated from bovine milk whey, to prevent Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Streptococcus agalactiae (S. agalactiae) and Pseudomonas aeruginosa (P. aerogenosa) growth and then evaluates its immunomodulator effect. First, bLf isolation was attempted from bovine milk whey using a cation exchange chromatography by SP-Sepharose. Second, the antimicrobial activity assays were trailed to study the antimicrobial activity of bLf. Finally, the immune effect of bLf was studied by lymphocyte transformation test. It was found that bLf was separated around molecular weight of 80 kDa and showed significant inhibitory effect against E. coli followed by P. aeruginosa, S. agalactiae and S. aureus. bLf increased lymphocyte transformations mean values in a dose dependant manner. The highest transformations mean value was determined at 50 μg/mL. In conclusion, these results suggest that bLf is a potent natural antimicrobials and immunomodulator agent.展开更多
Background: Growth retardation is a challenge in Bangladesh. School feeding programs with fortified biscuits have been evaluated in Bangladesh. However, the impacts of a school meal program using local foods on the gr...Background: Growth retardation is a challenge in Bangladesh. School feeding programs with fortified biscuits have been evaluated in Bangladesh. However, the impacts of a school meal program using local foods on the growth and nutritional status of children have not been investigated. Objective: To determine whether a school meal program (SMP) using local foods with soybean could improve children’s growth and micronutrient status in rural Bangladesh. Methods: Two primary schools were randomly assigned as intervention (SMP;n = 200) and control (non-SMP;n = 200) schools. Children in the intervention school were supplied a school meal with local foods including soybean, containing more than one-third of the recommended daily allowance of energy and nutrients, 5 days/week for 8 months. The attendance rate and school lunch consumption of the children were monitored. Baseline and final anthropometry, hemoglobin and micronutrient status were assessed. Results: There were no significant differences in anthropometric measurements at baseline between the intervention and control groups, but there were differences in the prevalence of anemia, vitamin A deficiency and zinc deficiency. After the intervention, children in the SMP school showed a larger degree of improvement in the height-for-age Z-score (P Conclusion: A school meal program using local foods with soybean improved the height velocity and hemoglobin concentration of children in rural Bangladesh.展开更多
Colon cancer is the third major cause of cancer deaths,accounting for about 8%in terms of mortality globally.The present study aims to explore the effect of silencing Astrocyte Elevated Gene-1(AEG-1),a metastasis medi...Colon cancer is the third major cause of cancer deaths,accounting for about 8%in terms of mortality globally.The present study aims to explore the effect of silencing Astrocyte Elevated Gene-1(AEG-1),a metastasis mediating factor,and how it interacts with Exostosin-1(EXT-1)protein to inhibit the proliferative and invasive potential in colon cancer cells.Forward siRNA transfection was performed using AEG-1 siRNA in SW480 and SW620 colon cancer cell lines,and the expression levels of mRNA and protein were analyzed by Real-time PCR and Immunofluorescence.A simple bioinformatics approach was carried out to identify the possible interactions between AEG-1 and EXT-1 using Easy Networks and Pathway Commons Database.Cell survival and clonal efficiency were determined using Cell Counting Kit-8 assay and clonogenic assay,apoptosis using flow cytometry analysis,migration and invasion using scratch and Transwell assays,respectively.Forward siRNA transfection significantly suppressed the expression of AEG-1 in mRNA and protein levels on SW480 and SW620 colon cancer cells.From our results,we found that EXT-1 mRNA and protein level was significantly upregulated in AEG-1 siRNA transfected cells.Moreover,treatment with AEG-1 siRNA inhibited the proliferation,clonogenic ability,migration,and invasion and also induced apoptosis.Through the bioinformatic approach,our data analyses pointed towards the crosstalk between AEG-1 and EXT-1 mediated through Patched-1(PTCH-1)protein.Our current results demonstrated that silencing AEG-1 can restrain cell proliferation,migration,and invasion,ultimately leading to apoptosis.In AEG-1 siRNA transfected cells,PTCH-1 activity might be modulated by several genes and,in turn,affects the EXT-1 activity.Collectively,these observations not only provide insight into the interplay between AEG-1 and EXT-1 but also suggest that AEG-1 may represent a possible candidate therapeutic target through interaction with EXT-1 in colon cancer.展开更多
The present study was conducted mainly to establish a new concomitant immunity model to Schistosoma mansoni in mice and assess its effects on the resistance of mice to a challenge infection with a possibility of using...The present study was conducted mainly to establish a new concomitant immunity model to Schistosoma mansoni in mice and assess its effects on the resistance of mice to a challenge infection with a possibility of using as a diagnostic marker. Three groups (A, B and C) of BALB/c mice were infected with a single dose of S. mansoni cercariae obtained from infected Biomphalaria glabrata snail. The group A mice were used as infected control group. The group B mice were intraperitoneally injected with allylthiourea (ATU) 22 days post-primary infection then they were challenged 3 weeks post-ATU treatment. The group C mice were challenged with the same number of cercariae 6 weeks post-primary infection. Perfusion of all mice was done 9 weeks after infection in order to obtain worm burdens. The livers of all mice were obtained for parasitological and pathological assessments. Our results showed that the group B mice had a 29.11% worm reduction rate, 25.37% liver egg reduction rate, and 37.48% granuloma size reduction rate compared to their respective controls. While the group C mice showed superior results and had a 54.66% worm reduction rate, 41.45% liver egg reduction rate, and 51.76% granuloma size reduction rate. It was concluded that these results described novel imaging methods that permit visualization of live schistosomes within their living hosts and may have important implications not only for epidemiological and diagnostic investigations, but also in designing control programs for schistosomiasis including anti-schistosome vaccine.展开更多
Background and Purpose: In Iraq, breast cancer is the common type of female malignancy. Increasing indication in the past 10 years proposes that Epstein-Barr virus (EBV) and cytomegalovirus (HCMV) are related with som...Background and Purpose: In Iraq, breast cancer is the common type of female malignancy. Increasing indication in the past 10 years proposes that Epstein-Barr virus (EBV) and cytomegalovirus (HCMV) are related with some human malignancies including breast cancer. The part of EBV and HCMV in breast cancer is still debatable. Unraveling this relationship is potentially?essential for better understanding of breast cancer etiology, early recognition and possibly inhibition of breast cancer The purpose of the current study is to detect the correlation between EBV,?HCMV and breast cancer in Iraqi women and expression of ERB and IL-6R in breast tissues. Patients and Methods: The study was done on paraffin-embedded?tissues of eighty Iraqi patients with breast cancer in addition to twenty normal breast tissues as controls. Both controls and breast cancer mass?are?divided into two sections, one for DNA extraction and amplification by real time PCR for detect EBV and HCMV occurrence while the other section processed for protein expression (IL-6R, ERB) by immunohistochemistry technique (IHC). Results: The result showed that 18/80 (22.5%) and 5/80 (6.25%) sample from breast cancer were positive for EBV and HCMV respectively, with the?p-value?= 0.062 and 0.597 and the results of IHC for IL-6R and ERB expression in patients with breast cancer were 37/80 (46.25%) and 30/80 (37.5%)?p-value?=?(0.274 and 0.381) respectively. Conclusions: Our findings suggest that EBV might have a role in the pathogenesis of breast cancer and absence this role between HCMV with breast cancer. These findings were based mainly on EBV, HCMV detection by PCR technique. So,?the rolesof these viruses in the development of breast cancer remain unclear.展开更多
基金Zanjan University of Medical Sciences supported the present study(Grant Number:A-12-1244-18).
文摘In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.
基金supported by Mashhad University of Medical Sciencesapproved by the Ethics Committee of Mashhad University of Medical Sciences(Ethics ID:IR.MUMS.REC.1400.144).
文摘Objective:To make evidence-based decisions based on broad mortality trends for Razavi Khorasan province,Iran.Methods:In order to determine the baseline number of deaths,we used univariate time series analyses for monthly data from the monthly vital statistics reports(From April 2015 to March 2022).For excess mortalities,these baselines were subtracted from reported deaths with a 95%prediction interval.To compare time and causes,a P-score was calculated.Results:From March 2020 to March 2022,there were 61949 registered deaths,and the estimated deaths with a 95%confidence interval(CI)were 43246.16(35718.28,50774.05).So,in 2020-2021 and 2021-2022,the death counts were 35.15%and 51.33%higher than projected.A total of 18666 cardiovascular diseases were reported and a total of 15704.46(12006.95,19401.96)was estimated.The P-score for this duration was 14.49%and 23.23%higher than expected.Infectious and parasitic diseases plus COVID-19 were 16633 and estimated to be 1044.87(456.77,1632.96).A total of 4420 diseases of the respiratory system were reported,and 4564.94 deaths were predicted(2277.43,6852.43).In the first year of the pandemic,the P-score dropped to-35.28%and in the second year,it jumped sharply to 22.38%.Conclusions:Excess mortality,along with cause-specific mortality,can be helpful for monitoring trends and developing public health policies at the local,national,and international levels.
文摘Liver transplant(LT)outcomes have markedly improved in the recent decades,even if long-term morbidity and mortality are still considerable.Most of late deaths are independent from graft function and different comorbidities,including complications of metabolic syndrome and de novo neoplasms,seem to play a key role in determining long-term outcomes in LT recipients.This review discusses the main factors associated with late mortality and suggests possible strategies to improve long-term management and follow-up after liver transplantation.In particular,the reduction of drug toxicity,the use of tools to identify high-risk patients,and setting up a multidisciplinary team also for long-term management of LT recipients may further improve survival after liver transplantation.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
文摘AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas.METHODS: We conducted a systematic review and meta-analysis of published studies. We searched Pub Med, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the Clinical Trials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes(recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's riskof-bias. Between-study heterogeneity was assessed, and pooled risk ratio(RR) estimates with their 95% confidence intervals(95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat(NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE.RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas(fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; randomeffects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20(95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance(fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.
文摘Phage display is very strong technique in drug discovery and development. Phage display has many applications in improving the immunological studies. Development of monoclonal antibody, peptides, peptidomimetics and epitope mapping are main application of phage display. Selection of monoclonal antibody or peptides that are displayed on the surface of the phages can be occurred through biopanning process. In biopanning process phage library is incubated with antigen and particular phages can be identified and isolated. Increasing the stringency in the biopanning rounds can be help to select phages with high affinity and specificity. Here, we describe an overview of phage display application with focusing on monoclonal antibody production and epitope mapping.
文摘In the last years,several studies have been focused on elucidate the role of tumor microenvironment(TME)in cancer development and progression.Within TME,cells from adaptive and innate immune system are one of the main abundant components.The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth.This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer,such as hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(iCCA).Liver is well-known to be an important immunological organ with unique microenvironment.Here,in normal conditions,the rich immune-infiltrating cells cooperate with non-parenchymal cells,such as liver sinusoidal endothelial cells and Kupffer cells,favoring self-tolerance against gut antigens.The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells,in order to understand how this cross-talk promotes tumor growth.Deeper attention is,in fact,focused on immune-based therapy for these tumors,as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment.In this review,we will examine the key pathways underlying TME cell-cell communications,with deeper focus on the role of natural killer cells in primary liver tumors,such as HCC and iCCA,as new opportunities for immune-based therapeutic strategies.
基金supported financially by Iran National Science Foundation(INSF)grant number 91004026
文摘Objective: To express human Vascular endothelial growth factor121(VEGF121) in insect cells. Methods: A gene construct containing VEGF was cloned in the p Fast Bac-HTA vector, followed by transformation in DH10 BAC. The recombinant bacmid was then extracted, and transfected into Sf9 insect cells. The transfected cells were harvested, and then VEGF expression was confirmed by Western blotting using specific antibodies. The tube formation assay was used for functional assessment of VEGF. Results: Our results showed that VEGF could be successfully expressed in the baculovirus system. Purified VEGF was able to stimulate in vitro tube formation of human endothelial cells. Conclusions: Results from this study demonstrated that the recombinantly-produced VEGF can be considered as a promising candidate for therapeutic purposes.
文摘Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.
文摘Differential diagnosis of supraventricular tachycardia (SVT) and ventricular tachycardia (VT) is of paramount importance for appropriate patient management. Several diagnostic algorithms for discrimination of VT and SVT based on surface electrocardiogram (ECG) analysis have been proposed. Following established diagnosis of VT,a specific origination tachycardia site can be supposed according to QRS complex characteristics. This review aims to cover comprehensive and comparative description of the main VT diagnostic algorithms and to present ECG characteristics which permit to suggest the most common VT origination sites.
文摘Neurodegenerative diseases(NDs)are a growing health problem associated with a high burden due to destructive and longterm clinical effects.Cellular aggregations of misfolded proteins are the most common pathological hallmark of many late-onset NDs called proteinopathies including Parkinson’s disease(PD),Alzheimer’s disease(AD),tauopathies,amyotrophic lateral sclerosis(ALS),and polyglutamine(polyQ)expansion diseases such as Huntington’s disease(HD)and various spinocerebellar ataxias(SCA)such as SCA3(Renna et al.,2010).Misfolded proteins can be generated by posttranslational conjugation(e.g.,hyperphosphorylated tau in AD),or endoproteolytic cleavage(e.g.,amyloidβpeptides)or genetic mutations in specific proteins(such as HTT in HD,α-synuclein in PD,PrPC in prion disease and SOD1 and TDP-43 in ALS)leading to the formation of oligomers.
文摘Hepatitis C virus(HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells(DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs(pb DCs) that represent the most accessible source of DCs. These alterations include numerical reduction, impaired production of inflammatory cytokines and increased production of immunosuppressive IL10. These changes in DCs are relevant to our understanding the immune mechanisms underlying the propensity of HCV to establish persistent infection. Importantly, the noninvasive accessibility of pb DCs renders the analysis of these cells a convenient procedure that can be serially repeated in patient follow-up. Accordingly, the study of pb DCs in HCV-infected patients during conventional treatment with pegylated interferon and ribavirin indicated that restoration of normal plasmacytoid DC count may represent an additional mechanism contributing to the efficacy of the dual therapy. It also identified the pre-treatment levels of plasmacytoid DCs and IL10 as putative predictors of response to therapy. Treatment of chronic HCV infection is changing, as new generation direct-acting antiviral agents will soon be available for use in interferon-free therapeutic strategies. The phenotypic and functional analysis of pb DCs in this novel therapeutic setting will provide a valuable tool for investigating mechanisms underlying treatment efficacy and for identifying predictors of treatment response.
文摘Wilson’s disease(WD)is a rare inherited disorder of human copper metabolism,with an estimated prevalence of 1:30000-1:50000 and a broad spectrum of hepatic and neuropsychiatric manifestations.In healthy individuals,the bile is the main route of elimination of copper.In WD patients,copper accumulates in the liver,it is released into the bloodstream,and is excreted in urine.Copper can also be accumulated in the brain,kidneys,heart,and osseous matter and causes damage due to direct toxicity or oxidative stress.Hepatic WD is commonly but not exclusively diagnosed in childhood or young adulthood.Adherent,non-cirrhotic WD patients seem to have a normal life expectancy.Nevertheless,chronic management of patients with Wilson’s disease is challenging,as available biochemical tests have many limitations and do not allow a clear identification of non-compliance,overtreatment,or treatment goals.To provide optimal care,clinicians should have a complete understanding of these limitations and counterbalance them with a thorough clinical assessment.The aim of this review is to provide clinicians with practical tools and suggestions which may answer doubts that can arise during chronic management of patients with hepatic WD.In particular,it summarises current knowledge on Wilson’s disease clinical and biochemical monitoring and treatment.It also analyses available evidence on pregnancy and the role of low-copper diet in WD.Future research should focus on trying to provide new copper metabolism tests which could help to guide treatment adjustments.
文摘AIM To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus(HBV)-infected patients in the Tuscan public health care system.METHODS This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS Of 4015 chronic viral hepatitis patients, 1096(27.3%) were HBV infected. The case report form was correctly completed for only 833 patients(64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years(only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures(23%), mother-to-child(17%) and sexual transmission(12%). The most represented HBV genotypes were D(72%) and A(14%). Of the patients, 24.7% of patients were HBe Ag positive, and 75.3% were HBe Ag negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic(35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.
文摘BACKGROUND Branch duct-intraductal papillary mucinous neoplasms(BD-IPMNs)are the most common pancreatic cystic tumours and have a low risk of malignant transformation.Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure,especially when comparing different methods.On the other side,cyst volume is a new parameter with low interobserver variability and is highly reproducible over time.AIM To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics.METHODS Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed.The diameter was measured on three planes,while the volume was calculated by segmentation:The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion;therefore,a threedimensional volume of interest was finally obtained with the calculated value expressed in cm^(3).Changes in size over time were measured.The development of worrisome features was evaluated.RESULTS We evaluated exams of 98 patients across a 40.5-mo median follow-up time.Ten patients developed worrisome features.Cysts at baseline were significantly larger in patients who developed worrisome features(diameters P=0.0035,P=0.00652,P=0.00424;volume P=0.00222).Volume growth rate was significantly higher in patients who developed worrisome features(1.12 cm^(3)/year vs 0 cm^(3)/year,P=0.0001);diameter growth rate was higher as well,but the difference did not always reach statistical significance.Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features(0.46 cm^(3)/year vs 0 cm^(3)/year,P=0.00634).CONCLUSION The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs.Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.
文摘The antibiotic therapy has many problems, such as antibiotics resistance, hypersensitivity, direct toxicity, antibiotic-induced immunosuppresion and super-infections. This is highlighting the need for a new strategy for non-antibiotic therapy through the use of novel immunomodulators as naturally released ones (Lactoferrin). The present study investigates the potential of bovine lactoferrin (bLf), isolated from bovine milk whey, to prevent Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Streptococcus agalactiae (S. agalactiae) and Pseudomonas aeruginosa (P. aerogenosa) growth and then evaluates its immunomodulator effect. First, bLf isolation was attempted from bovine milk whey using a cation exchange chromatography by SP-Sepharose. Second, the antimicrobial activity assays were trailed to study the antimicrobial activity of bLf. Finally, the immune effect of bLf was studied by lymphocyte transformation test. It was found that bLf was separated around molecular weight of 80 kDa and showed significant inhibitory effect against E. coli followed by P. aeruginosa, S. agalactiae and S. aureus. bLf increased lymphocyte transformations mean values in a dose dependant manner. The highest transformations mean value was determined at 50 μg/mL. In conclusion, these results suggest that bLf is a potent natural antimicrobials and immunomodulator agent.
文摘Background: Growth retardation is a challenge in Bangladesh. School feeding programs with fortified biscuits have been evaluated in Bangladesh. However, the impacts of a school meal program using local foods on the growth and nutritional status of children have not been investigated. Objective: To determine whether a school meal program (SMP) using local foods with soybean could improve children’s growth and micronutrient status in rural Bangladesh. Methods: Two primary schools were randomly assigned as intervention (SMP;n = 200) and control (non-SMP;n = 200) schools. Children in the intervention school were supplied a school meal with local foods including soybean, containing more than one-third of the recommended daily allowance of energy and nutrients, 5 days/week for 8 months. The attendance rate and school lunch consumption of the children were monitored. Baseline and final anthropometry, hemoglobin and micronutrient status were assessed. Results: There were no significant differences in anthropometric measurements at baseline between the intervention and control groups, but there were differences in the prevalence of anemia, vitamin A deficiency and zinc deficiency. After the intervention, children in the SMP school showed a larger degree of improvement in the height-for-age Z-score (P Conclusion: A school meal program using local foods with soybean improved the height velocity and hemoglobin concentration of children in rural Bangladesh.
基金supported by a grant from the Department of Science and Technology(DST)–Science and Engineering Research Board(SERB)(EMR/2017/001877)and Lady Tata Memorial Trust(LTMT)for providing the fellowship.
文摘Colon cancer is the third major cause of cancer deaths,accounting for about 8%in terms of mortality globally.The present study aims to explore the effect of silencing Astrocyte Elevated Gene-1(AEG-1),a metastasis mediating factor,and how it interacts with Exostosin-1(EXT-1)protein to inhibit the proliferative and invasive potential in colon cancer cells.Forward siRNA transfection was performed using AEG-1 siRNA in SW480 and SW620 colon cancer cell lines,and the expression levels of mRNA and protein were analyzed by Real-time PCR and Immunofluorescence.A simple bioinformatics approach was carried out to identify the possible interactions between AEG-1 and EXT-1 using Easy Networks and Pathway Commons Database.Cell survival and clonal efficiency were determined using Cell Counting Kit-8 assay and clonogenic assay,apoptosis using flow cytometry analysis,migration and invasion using scratch and Transwell assays,respectively.Forward siRNA transfection significantly suppressed the expression of AEG-1 in mRNA and protein levels on SW480 and SW620 colon cancer cells.From our results,we found that EXT-1 mRNA and protein level was significantly upregulated in AEG-1 siRNA transfected cells.Moreover,treatment with AEG-1 siRNA inhibited the proliferation,clonogenic ability,migration,and invasion and also induced apoptosis.Through the bioinformatic approach,our data analyses pointed towards the crosstalk between AEG-1 and EXT-1 mediated through Patched-1(PTCH-1)protein.Our current results demonstrated that silencing AEG-1 can restrain cell proliferation,migration,and invasion,ultimately leading to apoptosis.In AEG-1 siRNA transfected cells,PTCH-1 activity might be modulated by several genes and,in turn,affects the EXT-1 activity.Collectively,these observations not only provide insight into the interplay between AEG-1 and EXT-1 but also suggest that AEG-1 may represent a possible candidate therapeutic target through interaction with EXT-1 in colon cancer.
文摘The present study was conducted mainly to establish a new concomitant immunity model to Schistosoma mansoni in mice and assess its effects on the resistance of mice to a challenge infection with a possibility of using as a diagnostic marker. Three groups (A, B and C) of BALB/c mice were infected with a single dose of S. mansoni cercariae obtained from infected Biomphalaria glabrata snail. The group A mice were used as infected control group. The group B mice were intraperitoneally injected with allylthiourea (ATU) 22 days post-primary infection then they were challenged 3 weeks post-ATU treatment. The group C mice were challenged with the same number of cercariae 6 weeks post-primary infection. Perfusion of all mice was done 9 weeks after infection in order to obtain worm burdens. The livers of all mice were obtained for parasitological and pathological assessments. Our results showed that the group B mice had a 29.11% worm reduction rate, 25.37% liver egg reduction rate, and 37.48% granuloma size reduction rate compared to their respective controls. While the group C mice showed superior results and had a 54.66% worm reduction rate, 41.45% liver egg reduction rate, and 51.76% granuloma size reduction rate. It was concluded that these results described novel imaging methods that permit visualization of live schistosomes within their living hosts and may have important implications not only for epidemiological and diagnostic investigations, but also in designing control programs for schistosomiasis including anti-schistosome vaccine.
文摘Background and Purpose: In Iraq, breast cancer is the common type of female malignancy. Increasing indication in the past 10 years proposes that Epstein-Barr virus (EBV) and cytomegalovirus (HCMV) are related with some human malignancies including breast cancer. The part of EBV and HCMV in breast cancer is still debatable. Unraveling this relationship is potentially?essential for better understanding of breast cancer etiology, early recognition and possibly inhibition of breast cancer The purpose of the current study is to detect the correlation between EBV,?HCMV and breast cancer in Iraqi women and expression of ERB and IL-6R in breast tissues. Patients and Methods: The study was done on paraffin-embedded?tissues of eighty Iraqi patients with breast cancer in addition to twenty normal breast tissues as controls. Both controls and breast cancer mass?are?divided into two sections, one for DNA extraction and amplification by real time PCR for detect EBV and HCMV occurrence while the other section processed for protein expression (IL-6R, ERB) by immunohistochemistry technique (IHC). Results: The result showed that 18/80 (22.5%) and 5/80 (6.25%) sample from breast cancer were positive for EBV and HCMV respectively, with the?p-value?= 0.062 and 0.597 and the results of IHC for IL-6R and ERB expression in patients with breast cancer were 37/80 (46.25%) and 30/80 (37.5%)?p-value?=?(0.274 and 0.381) respectively. Conclusions: Our findings suggest that EBV might have a role in the pathogenesis of breast cancer and absence this role between HCMV with breast cancer. These findings were based mainly on EBV, HCMV detection by PCR technique. So,?the rolesof these viruses in the development of breast cancer remain unclear.
