BACKGROUND Numerous studies have shown that in Crohn’s disease(CD),the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract.Until recently,studies have ...BACKGROUND Numerous studies have shown that in Crohn’s disease(CD),the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract.Until recently,studies have focused almost exclusively on bacteria in the gut.Lately,more attention has been paid to the role of intestinal fungi.AIM To study the gut mycobiome analysis of pediatric patients with CD(in different stages of disease activity)compared to healthy children.METHODS Fecal samples were collected from patients:With active,newly diagnosed CD(n=50);active but previously diagnosed and treated CD(n=16);non-active CD and who were in clinical remission(n=39)and from healthy volunteers(n=40).Fungal DNA was isolated from the samples.Next,next generation sequencing(MiSeq,Illumina)was performed.The composition of mycobiota was correlated with clinical and blood parameters.RESULTS Candida spp.were overrepresented in CD patients,while in the control group,the most abundant genus was Saccharomyces.In CD patients,the percentage of Malassezia was almost twice that of the control(P<0.05).In active CD patients,we documented a higher abundance of Debaryomyces hansenii(D.hansenii)compared to the non-active CD and control(P<0.05)groups.Moreover,statistically significant changes in the abundance of Mycosphaerella,Rhodotorula,and Microidium were observed.The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population.Moreover,we have documented statistically significant correlations between:D.hansenii and patient age(negative);C.zeylanoides and patient age(positive);C.dubliniensis and calprotectin(positive);C.sake and calprotectin(positive);and C.tropicalis and pediatric CD activity index(PCDAI)(positive).CONCLUSION Mycobiome changes in CD patients,and the positive correlation of some species with calprotectin or PCDAI,give strong evidence that fungi may be of key importance in the development of CD.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to trea...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.展开更多
Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism betwee...Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.展开更多
Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle g...Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.展开更多
AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective ...AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell line.METHODS:UMB-containing niosomes were created,optimized,and characterized.RPE-like cells were treated with free UMB and UMB-containing niosomes.The IC_(50)values of the treatments were determined using an MTT assay.Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis.Niosomes’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were assessed.Free UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/mL.RESULTS:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free UMB.CONCLUSION:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression.However,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual delivery.These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.展开更多
Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and ...Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AI...BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.展开更多
Aim: A standardized preparation of seeds and shells of selected sub-species of Rosa canina L, trade name Hyben Vital, reduces discomfort from osteoarthritis of the knee and hip. This study aims to investigate the impa...Aim: A standardized preparation of seeds and shells of selected sub-species of Rosa canina L, trade name Hyben Vital, reduces discomfort from osteoarthritis of the knee and hip. This study aims to investigate the impact of the same rose-hip powder (RHP) on discomfort and the consumption of rescue medication, in patients with osteoarthritis of the hand. Methods: The double blind, placebo-controlled, crossover trial included 30 patients with osteoarthritis of the dominant hand. Patients were randomly allocated to treatment with either five gram encapsulated RHP or placebo, for three months (Phase 1), after which they switched to the corresponding treatment for a further three months period (Phase 2). Before entering the study, after 3 weeks and following three months of each of the study phases, scores for pain, stiffness and general feeling of discomfort were evaluated using a 10 step categorical scale, focusing on 16 different daily activities of the hand. The consumption of rescue medication was also calculated at the beginning and at the end of each study phase. Data are based on the intention to treat. Results: At the end of Phase 1, 90% of patients in the group receiving RHP first (group A), showed a reduction in pain, as compared to 36% in the group B initially given placebo (p 0.029). In line with this observation, stiffness and the general feeling of discomfort from the disease declined during RHP treatment (p 0.032). In group A, symptom reduction was still indicated by the study subjects 3 weeks after the switch to placebo. The consumption of rescue medication such as paracetamol, codeine and tramadol also declined significantly in group A when compared to group B (p 0.013). Conclusion: The present data suggest that administration of RHP, containing seeds and shells can reduce symptoms of osteoarthritis of the hand and consumption of rescue medication.展开更多
Background: Acanthosis nigricans is a well known cause of facial melanosis in Iraqi males and usually it is a part of ordinary acanthosis nigricans. It is commonly associated with many metabolic derangements. Objectiv...Background: Acanthosis nigricans is a well known cause of facial melanosis in Iraqi males and usually it is a part of ordinary acanthosis nigricans. It is commonly associated with many metabolic derangements. Objectives: To evaluate cases of acanthosis nigricans of the face for all metabolic disturbances including fasting blood sugar, fasting serum insulin, total cholesterol, triglyceride, growth hormone and serum leptin. Patients and Methods: Twenty seven cases of acanthosis nigricans of the face were included in this case descriptive, clinical and biochemical study. This was conducted in Department of Dermatology-Baghdad Teaching Hospital and Department of Clinical Biochemistry, College of Medicine, Baghdad, Iraq during the period from November 2012-August 2014. It consisted of 26 males and one female, their ages ranged from 16 - 58 (39 ± 4.9) years. The diagnosis was established by clinical and histopathological evaluation. Sharquie’s ANSI scoring of acanthosis nigricans of face was carried out for all patients, also body mass index was assessed. Biochemical evaluation was carried out for all patients including total cholesterol, triglyceride, fasting blood sugar and insulin, insulin resistance, growth hormone and leptin enzyme immunoassay. Twenty seven healthy control non obese individuals with comparable ages and gender were assessed for all tests. Results: Biochemical results showed that fasting blood glucose, fasting serum insulin, insulin resistance, fasting serum triglyceride, total cholesterol, growth hormone and serum leptin were statistically significantly high in patients with acanthosis nigricans of the face in comparison with control individuals and all were positively correlated with the scoring of acanthosis nigricans of the face apart from high density lipoprotein was negatively correlated. Conclusion: Acanthosis nigricans of the face is a good marker for the associated metabolic diseases and these metabolic changes were statistically significantly correlated with the severity of acanthosis nigricans.展开更多
Objective:To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome(PCOS)rats.Methods:Fifty female Sprague-Dawley rats were randomly divided int...Objective:To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome(PCOS)rats.Methods:Fifty female Sprague-Dawley rats were randomly divided into five groups:the control group,the ethanol group,the quercetin group(15 mg/kg/day),the PCOS group,as well as the PCOS+quercetin group.After the induction of PCOS,quercetin was administered orally for 30 days.Histological,stereological and real-time PCR analyses were carried out to evaluate the effect of quercetin on PCOS rats.Results:Stereological analysis revealed that quercetin significantly increased the number of ovarian follicles and the volume of corpus luteum and induced a significant decrease in atretic follicles in comparison to the PCOS group.In addition,quercetin markedly increased mTOR gene expression while decreasing Beclin-1 and LC3 gene expression.Conclusions:Quercetin strongly modulates the expression of ovarian autophagy-related genes and stereological parameters in PCOS rats.Therefore,it can be considered as an ameliorative component for ovarian follicular impairments.展开更多
Heat exchanger is an important equipment used in process industries for cooling and heating purposes. Its design configuration which involves the flow of cold and hot fluids within the exchanger subjects it to corrosi...Heat exchanger is an important equipment used in process industries for cooling and heating purposes. Its design configuration which involves the flow of cold and hot fluids within the exchanger subjects it to corrosion attack. The article utilized the principle of mass and energy conservation in the development of weight and temperature models to study the effect of corrosion on mild steel coupon inside the exchanger containing water and Mono ethanol amine (MEA). The models developed were resolved analytically using Laplace Transform and simulated using Excel as simulation tool and data obtained from experiment in the laboratory to obtain profiles of weight loss and temperature as a function of time. The weight loss and performance of mild steel under various corrosive conditions were examined which indicates the effect of corrosion on the mild steel heat exchanger in water and MEA media. The result shows that water is more corrosive than MEA at higher temperatures and at lower temperatures of 35°C and 1 atm, MEA has inhibitive properties than water as indicated by the weight loss result with time. The comparative analysis between the results obtained from the model simulation and experimental results shows that the result obtained from the model is more reliable and demonstrated better performance characteristics as it clearly shows mild steel heat exchanger experiences more corrosive effect in water medium than MEA at higher temperatures. And at lower temperatures, MEA becomes more inhibitive and less corrosive than water. The model simulation results correlate with various literatures and hence, it is valid for future referencing.展开更多
AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rat...AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.展开更多
Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer(CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and veget...Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer(CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase(PI3K) expression, Ak strain transforming phosphorylation,m TOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.展开更多
AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: Th...AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.展开更多
Objective:To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells.Methods:Ellagic acid(10-100 mol/L) treatment(48 h) of human prostate carcinoma PC3 cells was found to res...Objective:To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells.Methods:Ellagic acid(10-100 mol/L) treatment(48 h) of human prostate carcinoma PC3 cells was found to result in a dose-dependent inhibition of cell growth and apoptosis of PC3 cells as assessed by MTT assay,western blotting.flow cytometry and confocal microscopy.Results:We observed that ellagic acid treatment of PC3 cells resulted in a dose dependent inhibition of cell growth/cell viability.This ellagic acid caused cell growth inhibition was found to be accompanied by induction of apoptosis,as assessed by the cleavage of poly (ADP-ribose) polymerase(PARP) and morphological changes.Further,induction of apoptosis accompanied a decrease in the levels of antiapoptotic protein Bcl-2 and increase in proapoptotic protein Bax.thus shifting the Bax:Bcl-2 ratio in favor of apoptosis.Ellagic acid treatment of PC3 cells was also found to result in significant activation of caspases,as shown by the dose dependent decrease in the protein expression of procaspase-3,-6.-8 and -9.This ellagic acid-mediated induction of apoptosis was significantly(80%-90%) inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone(Z-VAD-FMK).Thus these data suggested an essential role of caspases in ellagic acid-mediated apoptosis of PC3 cells.Conclusions:It is tempting to suggest that consumption of tropical pigmented fruits and vegetables could be an effective strategy to combat prostate cancer.展开更多
AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and...AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore(LC-Red 640).Real time quantitative polymerase chain reaction(PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues.In the patients group,carcinoembryonic antigen(CEA) and CA19-9 tumor markers were also measured immunochemically.RESULTS:Wild type survivin mRNA isoform was expressed in 48%of the 52 tumor samples,survivin-2b in 38%and survivin-ΔΕx3 in 29%,while no expression was found in normal tissues.The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b,survivin-ΔΕx3,survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin(P<0.001).The mRNA expression of wildsurvivin and survivin-ΔΕx3 was related with tumor size and invasion(P=0.006 and P<0.005,respectively).A significant difference was found between survivin-2b and morphologic cancer type.Also,the ratio of survivin-ΔEx3/ wild-survivin was significantly associated with prognosis.No association was observed between the three isoforms and grade,metastasis,Dukes stage and gender.The three isoforms were not correlated with CEA and CA19-9.CONCLUSION:Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.展开更多
Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and...Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.展开更多
Objective:To evaluate the possible association between Toll-interleukin 1 receptor(TIR) domain containing adaptor protein(TIRAP;also known as MAI.) rsl893352 and rs8l77374(S180L) gene polymorphisms and pulmonary tuber...Objective:To evaluate the possible association between Toll-interleukin 1 receptor(TIR) domain containing adaptor protein(TIRAP;also known as MAI.) rsl893352 and rs8l77374(S180L) gene polymorphisms and pulmonary tuberculosis(PTB) in a sample of Iranian population.Methods:This case-control study was performed on 174 PTB and 177 healthy subjects.Tetra amplification refractory mutation systetn-polymerase chain reaction(T-AKMS-PCR) was used to detect the polymorphisms.Results:Our finding showed that neither the overall Ckisqaare comparison of PTB and control subjects nor the logistic regression analysis indicated any association between rsl893352 polymorphism and PTB.Regarding rs8l77374 polymorphism,the CT genotype as well as CT+TT increased the risk of PTB in comparison with CC genotype(OR=4.73,95%CI=2.65-8.45,P<0.0001 and OR=6.47,95%C1=3.68-11.38,P<0.0001.respectively).The rs8177374 T allele increased the risk of PTB in comparison with C allele(OR=4.21.95%CI=2.43-7.26,P<0.0001).Conclusions:Our finding indicates that TIRAP rs8177374 polymorphism is associated with PTB in a sample of Iranian population.展开更多
AIM:To investigate the relationship between the metabolism of polyunsaturated fatty acids(PUFAs)andtumor-associated factors for predicting the outcome of colorectal carcinoma(CRC)in Chinese patients.METHODS:Fresh-froz...AIM:To investigate the relationship between the metabolism of polyunsaturated fatty acids(PUFAs)andtumor-associated factors for predicting the outcome of colorectal carcinoma(CRC)in Chinese patients.METHODS:Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography.The levels of vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2),prostaglandin E2 and platelet-derived growth factor(PDGF)were measured by enzyme-linked immunosorbent assay,and the levels of VEGF,p53 and Ki-67 were measured by immunohistochemistry.RESULTS:In malignant tissue,compared with normal tissue,the levels of totalω-6 PUFAs(24.64%±3.41%vs 26.77%±3.37%,P=0.00)and linoleic acid(LA)(15.46%±3.51%vs 18.30%±2.83%,P<0.01)were lower,whereas the levels of totalω-3 PUFAs(1.58%±0.74%vs 1.35%±0.60%,P<0.01)and dihomo-gamma-linolenic acid(DGLA)(1.32%±0.69%vs 0.85%±0.29%,P<0.01)were significantly higher.The ratios of arachidonic acid(AA)/LA(0.53±0.22 vs0.42±0.19,P<0.01)and AA/totalω-6 PUFAs(0.31±0.09 vs 0.27±0.10,P<0.01)were also significantly higher in malignant tissue.The levels of PDGF(353.10±148.85 pg/m L vs 286.09±104.91 pg/m L,P<0.01),COX-2(125.21±70.29 ng/m L vs 67.06±42.22 ng/m L,P<0.01)and VEGF(357.11±128.76 pg/m L vs211.38±99.47 pg/m L,P<0.01)were also higher in malignant tissue compared to normal tissue.COX-2was inversely correlated with LA(R=-0.3244,P<0.05)and positively correlated with AA/totalω-6 PUFAs(R=0.3083,P<0.05)and AA/LA(R=0.3001,P<0.05).The tissue level of LA was highest in poorly differentiated tumors(19.9%±6.3%,P<0.05),while the ratio of AA/ω-3 PUFAs was lowest in these tumors(10.8±2.6,P<0.05).In VEGF-positive tumors,the level of LA was higher(16.2%±3.7%vs 13.9%±2.7%,P<0.01),while the AA/ω-3PUFA,AA/ω-6 PUFA,and AA/LA ratios were lower than in VEGF-negativetumors(5.0±1.8 vs 6.7±3.3,0.30±0.09 vs 0.34±0.09,0.50±0.21 vs 0.61±0.21,P<0.01).CONCLUSION:The metabolism of PUFAs may playan important role in the evolution of inflammationdriven tumorigenesis in CRC and may be considered apotential marker for prognosis.展开更多
Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In...Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.展开更多
基金Supported by National Science Centre(Poland),No.2019/33/N/NZ5/00698.
文摘BACKGROUND Numerous studies have shown that in Crohn’s disease(CD),the gut microbiota is of great importance in the induction and maintenance of inflammation in the gastrointestinal tract.Until recently,studies have focused almost exclusively on bacteria in the gut.Lately,more attention has been paid to the role of intestinal fungi.AIM To study the gut mycobiome analysis of pediatric patients with CD(in different stages of disease activity)compared to healthy children.METHODS Fecal samples were collected from patients:With active,newly diagnosed CD(n=50);active but previously diagnosed and treated CD(n=16);non-active CD and who were in clinical remission(n=39)and from healthy volunteers(n=40).Fungal DNA was isolated from the samples.Next,next generation sequencing(MiSeq,Illumina)was performed.The composition of mycobiota was correlated with clinical and blood parameters.RESULTS Candida spp.were overrepresented in CD patients,while in the control group,the most abundant genus was Saccharomyces.In CD patients,the percentage of Malassezia was almost twice that of the control(P<0.05).In active CD patients,we documented a higher abundance of Debaryomyces hansenii(D.hansenii)compared to the non-active CD and control(P<0.05)groups.Moreover,statistically significant changes in the abundance of Mycosphaerella,Rhodotorula,and Microidium were observed.The analyses at the species level and linear discriminant analysis showed that in each group it was possible to distinguish a specific species characteristic of a given patient population.Moreover,we have documented statistically significant correlations between:D.hansenii and patient age(negative);C.zeylanoides and patient age(positive);C.dubliniensis and calprotectin(positive);C.sake and calprotectin(positive);and C.tropicalis and pediatric CD activity index(PCDAI)(positive).CONCLUSION Mycobiome changes in CD patients,and the positive correlation of some species with calprotectin or PCDAI,give strong evidence that fungi may be of key importance in the development of CD.
基金Supported by the Chongqing Science and Health Joint Medical Research Project,No.2022MSXM133the First Batch of Key Disciplines on Public Health in Chongqing,Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.
文摘Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.
基金supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III(CD21/00138).PLV,DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139)TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Tomas Pinos,Grant No.PI22/00201).
文摘Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.
基金Supported by Stem Cell Research Center of Golestan University of Medical Sciences(No.110480).
文摘AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell line.METHODS:UMB-containing niosomes were created,optimized,and characterized.RPE-like cells were treated with free UMB and UMB-containing niosomes.The IC_(50)values of the treatments were determined using an MTT assay.Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis.Niosomes’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were assessed.Free UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/mL.RESULTS:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free UMB.CONCLUSION:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression.However,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual delivery.These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.
文摘Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. Methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μM) inhibited the production of superoxides and MPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. MPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.
文摘BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.
文摘Aim: A standardized preparation of seeds and shells of selected sub-species of Rosa canina L, trade name Hyben Vital, reduces discomfort from osteoarthritis of the knee and hip. This study aims to investigate the impact of the same rose-hip powder (RHP) on discomfort and the consumption of rescue medication, in patients with osteoarthritis of the hand. Methods: The double blind, placebo-controlled, crossover trial included 30 patients with osteoarthritis of the dominant hand. Patients were randomly allocated to treatment with either five gram encapsulated RHP or placebo, for three months (Phase 1), after which they switched to the corresponding treatment for a further three months period (Phase 2). Before entering the study, after 3 weeks and following three months of each of the study phases, scores for pain, stiffness and general feeling of discomfort were evaluated using a 10 step categorical scale, focusing on 16 different daily activities of the hand. The consumption of rescue medication was also calculated at the beginning and at the end of each study phase. Data are based on the intention to treat. Results: At the end of Phase 1, 90% of patients in the group receiving RHP first (group A), showed a reduction in pain, as compared to 36% in the group B initially given placebo (p 0.029). In line with this observation, stiffness and the general feeling of discomfort from the disease declined during RHP treatment (p 0.032). In group A, symptom reduction was still indicated by the study subjects 3 weeks after the switch to placebo. The consumption of rescue medication such as paracetamol, codeine and tramadol also declined significantly in group A when compared to group B (p 0.013). Conclusion: The present data suggest that administration of RHP, containing seeds and shells can reduce symptoms of osteoarthritis of the hand and consumption of rescue medication.
文摘Background: Acanthosis nigricans is a well known cause of facial melanosis in Iraqi males and usually it is a part of ordinary acanthosis nigricans. It is commonly associated with many metabolic derangements. Objectives: To evaluate cases of acanthosis nigricans of the face for all metabolic disturbances including fasting blood sugar, fasting serum insulin, total cholesterol, triglyceride, growth hormone and serum leptin. Patients and Methods: Twenty seven cases of acanthosis nigricans of the face were included in this case descriptive, clinical and biochemical study. This was conducted in Department of Dermatology-Baghdad Teaching Hospital and Department of Clinical Biochemistry, College of Medicine, Baghdad, Iraq during the period from November 2012-August 2014. It consisted of 26 males and one female, their ages ranged from 16 - 58 (39 ± 4.9) years. The diagnosis was established by clinical and histopathological evaluation. Sharquie’s ANSI scoring of acanthosis nigricans of face was carried out for all patients, also body mass index was assessed. Biochemical evaluation was carried out for all patients including total cholesterol, triglyceride, fasting blood sugar and insulin, insulin resistance, growth hormone and leptin enzyme immunoassay. Twenty seven healthy control non obese individuals with comparable ages and gender were assessed for all tests. Results: Biochemical results showed that fasting blood glucose, fasting serum insulin, insulin resistance, fasting serum triglyceride, total cholesterol, growth hormone and serum leptin were statistically significantly high in patients with acanthosis nigricans of the face in comparison with control individuals and all were positively correlated with the scoring of acanthosis nigricans of the face apart from high density lipoprotein was negatively correlated. Conclusion: Acanthosis nigricans of the face is a good marker for the associated metabolic diseases and these metabolic changes were statistically significantly correlated with the severity of acanthosis nigricans.
基金This work was supported by the Shiraz University of Medical Sciences(grant number:10774).
文摘Objective:To examine the effect of quercetin on stereological parameters and autophagy-related genes in ovaries of polycystic ovary syndrome(PCOS)rats.Methods:Fifty female Sprague-Dawley rats were randomly divided into five groups:the control group,the ethanol group,the quercetin group(15 mg/kg/day),the PCOS group,as well as the PCOS+quercetin group.After the induction of PCOS,quercetin was administered orally for 30 days.Histological,stereological and real-time PCR analyses were carried out to evaluate the effect of quercetin on PCOS rats.Results:Stereological analysis revealed that quercetin significantly increased the number of ovarian follicles and the volume of corpus luteum and induced a significant decrease in atretic follicles in comparison to the PCOS group.In addition,quercetin markedly increased mTOR gene expression while decreasing Beclin-1 and LC3 gene expression.Conclusions:Quercetin strongly modulates the expression of ovarian autophagy-related genes and stereological parameters in PCOS rats.Therefore,it can be considered as an ameliorative component for ovarian follicular impairments.
文摘Heat exchanger is an important equipment used in process industries for cooling and heating purposes. Its design configuration which involves the flow of cold and hot fluids within the exchanger subjects it to corrosion attack. The article utilized the principle of mass and energy conservation in the development of weight and temperature models to study the effect of corrosion on mild steel coupon inside the exchanger containing water and Mono ethanol amine (MEA). The models developed were resolved analytically using Laplace Transform and simulated using Excel as simulation tool and data obtained from experiment in the laboratory to obtain profiles of weight loss and temperature as a function of time. The weight loss and performance of mild steel under various corrosive conditions were examined which indicates the effect of corrosion on the mild steel heat exchanger in water and MEA media. The result shows that water is more corrosive than MEA at higher temperatures and at lower temperatures of 35°C and 1 atm, MEA has inhibitive properties than water as indicated by the weight loss result with time. The comparative analysis between the results obtained from the model simulation and experimental results shows that the result obtained from the model is more reliable and demonstrated better performance characteristics as it clearly shows mild steel heat exchanger experiences more corrosive effect in water medium than MEA at higher temperatures. And at lower temperatures, MEA becomes more inhibitive and less corrosive than water. The model simulation results correlate with various literatures and hence, it is valid for future referencing.
文摘AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.
文摘Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer(CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors.The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site(Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2(CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α(PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase(PI3K) expression, Ak strain transforming phosphorylation,m TOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation.These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.
文摘AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis(NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH.METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome(Met S) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients receivedlifestyle advice and were treated for a 12 mo period with rosuvastatin(10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid(SUA), high sensitivity C reactive protein(hs CRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values.RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20 th, which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3rd treatment month(ANOVA P < 0.001), while alkaline phosphatase activities by the 6th treatment month(ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced(P < 0.001). Lipid values were normalised by the 3rd treatment month. No patient had Met S by the 9th treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group.CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve Met S within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.
基金the College of Medicine Research Center (CMRC), Abha, College of Medicine, King Khalid University, Kingdom of Saudi Arabia for granting this study
文摘Objective:To evaluate the effect of allagic acid treatment on the cell viability of human prostate cancer cells.Methods:Ellagic acid(10-100 mol/L) treatment(48 h) of human prostate carcinoma PC3 cells was found to result in a dose-dependent inhibition of cell growth and apoptosis of PC3 cells as assessed by MTT assay,western blotting.flow cytometry and confocal microscopy.Results:We observed that ellagic acid treatment of PC3 cells resulted in a dose dependent inhibition of cell growth/cell viability.This ellagic acid caused cell growth inhibition was found to be accompanied by induction of apoptosis,as assessed by the cleavage of poly (ADP-ribose) polymerase(PARP) and morphological changes.Further,induction of apoptosis accompanied a decrease in the levels of antiapoptotic protein Bcl-2 and increase in proapoptotic protein Bax.thus shifting the Bax:Bcl-2 ratio in favor of apoptosis.Ellagic acid treatment of PC3 cells was also found to result in significant activation of caspases,as shown by the dose dependent decrease in the protein expression of procaspase-3,-6.-8 and -9.This ellagic acid-mediated induction of apoptosis was significantly(80%-90%) inhibited by the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone(Z-VAD-FMK).Thus these data suggested an essential role of caspases in ellagic acid-mediated apoptosis of PC3 cells.Conclusions:It is tempting to suggest that consumption of tropical pigmented fruits and vegetables could be an effective strategy to combat prostate cancer.
文摘AIM:To investigate three isoforms of survivin in colorectal adenocarcinomas.METHODS:We used the LightCycler Technology(Roche),along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore(LC-Red 640).Real time quantitative polymerase chain reaction(PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues.In the patients group,carcinoembryonic antigen(CEA) and CA19-9 tumor markers were also measured immunochemically.RESULTS:Wild type survivin mRNA isoform was expressed in 48%of the 52 tumor samples,survivin-2b in 38%and survivin-ΔΕx3 in 29%,while no expression was found in normal tissues.The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b,survivin-ΔΕx3,survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin(P<0.001).The mRNA expression of wildsurvivin and survivin-ΔΕx3 was related with tumor size and invasion(P=0.006 and P<0.005,respectively).A significant difference was found between survivin-2b and morphologic cancer type.Also,the ratio of survivin-ΔEx3/ wild-survivin was significantly associated with prognosis.No association was observed between the three isoforms and grade,metastasis,Dukes stage and gender.The three isoforms were not correlated with CEA and CA19-9.CONCLUSION:Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.
文摘Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.
文摘Objective:To evaluate the possible association between Toll-interleukin 1 receptor(TIR) domain containing adaptor protein(TIRAP;also known as MAI.) rsl893352 and rs8l77374(S180L) gene polymorphisms and pulmonary tuberculosis(PTB) in a sample of Iranian population.Methods:This case-control study was performed on 174 PTB and 177 healthy subjects.Tetra amplification refractory mutation systetn-polymerase chain reaction(T-AKMS-PCR) was used to detect the polymorphisms.Results:Our finding showed that neither the overall Ckisqaare comparison of PTB and control subjects nor the logistic regression analysis indicated any association between rsl893352 polymorphism and PTB.Regarding rs8l77374 polymorphism,the CT genotype as well as CT+TT increased the risk of PTB in comparison with CC genotype(OR=4.73,95%CI=2.65-8.45,P<0.0001 and OR=6.47,95%C1=3.68-11.38,P<0.0001.respectively).The rs8177374 T allele increased the risk of PTB in comparison with C allele(OR=4.21.95%CI=2.43-7.26,P<0.0001).Conclusions:Our finding indicates that TIRAP rs8177374 polymorphism is associated with PTB in a sample of Iranian population.
文摘AIM:To investigate the relationship between the metabolism of polyunsaturated fatty acids(PUFAs)andtumor-associated factors for predicting the outcome of colorectal carcinoma(CRC)in Chinese patients.METHODS:Fresh-frozen malignant and normal tissues from 82 Chinese patients with CRC were analyzed for PUFA composition using gas-liquid chromatography.The levels of vascular endothelial growth factor(VEGF),cyclooxygenase-2(COX-2),prostaglandin E2 and platelet-derived growth factor(PDGF)were measured by enzyme-linked immunosorbent assay,and the levels of VEGF,p53 and Ki-67 were measured by immunohistochemistry.RESULTS:In malignant tissue,compared with normal tissue,the levels of totalω-6 PUFAs(24.64%±3.41%vs 26.77%±3.37%,P=0.00)and linoleic acid(LA)(15.46%±3.51%vs 18.30%±2.83%,P<0.01)were lower,whereas the levels of totalω-3 PUFAs(1.58%±0.74%vs 1.35%±0.60%,P<0.01)and dihomo-gamma-linolenic acid(DGLA)(1.32%±0.69%vs 0.85%±0.29%,P<0.01)were significantly higher.The ratios of arachidonic acid(AA)/LA(0.53±0.22 vs0.42±0.19,P<0.01)and AA/totalω-6 PUFAs(0.31±0.09 vs 0.27±0.10,P<0.01)were also significantly higher in malignant tissue.The levels of PDGF(353.10±148.85 pg/m L vs 286.09±104.91 pg/m L,P<0.01),COX-2(125.21±70.29 ng/m L vs 67.06±42.22 ng/m L,P<0.01)and VEGF(357.11±128.76 pg/m L vs211.38±99.47 pg/m L,P<0.01)were also higher in malignant tissue compared to normal tissue.COX-2was inversely correlated with LA(R=-0.3244,P<0.05)and positively correlated with AA/totalω-6 PUFAs(R=0.3083,P<0.05)and AA/LA(R=0.3001,P<0.05).The tissue level of LA was highest in poorly differentiated tumors(19.9%±6.3%,P<0.05),while the ratio of AA/ω-3 PUFAs was lowest in these tumors(10.8±2.6,P<0.05).In VEGF-positive tumors,the level of LA was higher(16.2%±3.7%vs 13.9%±2.7%,P<0.01),while the AA/ω-3PUFA,AA/ω-6 PUFA,and AA/LA ratios were lower than in VEGF-negativetumors(5.0±1.8 vs 6.7±3.3,0.30±0.09 vs 0.34±0.09,0.50±0.21 vs 0.61±0.21,P<0.01).CONCLUSION:The metabolism of PUFAs may playan important role in the evolution of inflammationdriven tumorigenesis in CRC and may be considered apotential marker for prognosis.
基金supported by a grant from the Rafsanjan University of Medical Sciences(20/341/1395)
文摘Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF.