AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis an...AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.展开更多
Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antJoxJdant effects of res...Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antJoxJdant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide ＋ resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.展开更多
Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index(BMI) is associated with increased r...Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index(BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients(BMI ≥ 30 kg/m2) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m2 and those with BMI > 35 kg/m2 with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.展开更多
AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection....AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection.Liver energy metabolism was assessed in terms of lactate,pyruvate,lactate/pyruvate,ATP levels,lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities.In addition,membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products,measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase),catalase (CAT) and superoxide dismutase (SOD) activities.Liver DNA level,glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices.Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups.RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices.Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation.CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA,as well as improving cancer-cell sensitivity to chemotherapy.This is mediated through combating oxidative stress of free radicals,improving the energy metabolic state of the cell,and enhancing the activity of G6Pase,GST and AR enzymes.展开更多
Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes w...Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes were identified using in silico B-cell epitope prediction.A synthetic peptide analog of the predicted epitope was used to induce antipeptide IgY production in hens which was purified using affinity chromatography.Presence of purified IgY and its binding specificity were performed by gel electrophoresis and ELISA,respectively.Results:Out of the nine continuous epitopes identified,the sequence at position 193-208(LKVREDYSLECDPAVI)was selected and used to produce anti-peptide IgY.The produced IgY was found to bind to the synthetic analog of the Zika virus NS1 immunogenic epitope but not to other flaviviruses and random peptides from other pathogens.Conclusions:In this study,we identified an immunogenic epitope unique to Zika virus that can be used to develop a serodiagnostic tool that specifically detect Zika virus infection.展开更多
Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easil...Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easily isolated and cultured for a long time before losing their stem cell characteristics,which are self-renewal and pluripotency.AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics.They are easily accessible,and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells.It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression.These advantages have popularized its use in many fields including plastic reconstructive surgery.However,in the field of hepatology and liver transplantation,the progress is slower.AD-MSC have the potential to modulate inflammation,ameliorate ischemia-reperfusion injury,and support liver and biliary tract regeneration.These are very important for the treatment of various hepatobiliary diseases.Furthermore,the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis.We need alternative therapeutic approaches to treat end-stage liver failure.AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation.Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.展开更多
Objective:To clarify the modulatory effects of daily consumption of pomegranate extract(PE),olive oil(OO)andNagilla sativaoil(NSO)on antioxidant activity,sperm quality and pituitary-testicular axis of adult male wista...Objective:To clarify the modulatory effects of daily consumption of pomegranate extract(PE),olive oil(OO)andNagilla sativaoil(NSO)on antioxidant activity,sperm quality and pituitary-testicular axis of adult male wistar rats.Methods:Thirty-two adult male Wistar rats were dividedinto four equal groups,eight rats each.Using rat gastric tubes,1.0 mL distilled water,1.0 mL PE,0.4mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first,second,third andfourth groups,respectively.Reproductive organs,body weight,sperm criteria,testosterone,FSH,LH,inhibin-B,lipid peroxidation,and antioxidant enzyme activities were investigated.At the endof the study protocol,analyses occurred at the same time.Data were analysed by ANOVA test and P<0.05 was considered to be a significant value.Results:In all studied groups,malondialdehydelevel was significantly decreased accompanied with an increases in glutathione peroxidase andglutathione.Rats treated with PE showed an increase in catalase activities accompanied withan increase in sperm concentration which was also observed in NSO group.In PE treated group,sperm motility was also increased accompanied with decreased abnormal sperm rate.NSO,OOand PE treated groups shows an insignificant effect on testosterone,inhibin-B,FSH and LH incomparison with control group.Conclusions:These results show that administration of PE,NSOand OO could modify sperm characteristics and antioxidant activity of adult male wistar rats.展开更多
Breast cancer(BC)is the most common heterogeneous disease in women and one of the leading causes of cancer-related death.Surgery,chemotherapy,radiotherapy,hormone,and targeted therapy are the gold standards for BC tre...Breast cancer(BC)is the most common heterogeneous disease in women and one of the leading causes of cancer-related death.Surgery,chemotherapy,radiotherapy,hormone,and targeted therapy are the gold standards for BC treatment.One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics,resistance that severely limits the use and effectiveness of the drugs used for BC treatment.Therefore,it is essential to develop new strategies to improve therapeutic efficacy.Circular RNAs(circRNAs)are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′,and 3′;ends.Accumulating evidence suggests that circRNAs have a vital role in cancer development,progression,and BC resistance to chemotherapy.The purpose of this review is to discuss the biological properties of circRNAs,and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment,by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance,such as drug efflux,apoptosis dysfunction,autophagy,and DNA damage repair.CircRNAs are associated with drug resistance via ATP-binding cassette(ABC)efflux transporters,while some others by inhibition of cell apoptosis,thus leading to resistance to tamoxifen in BC cells.In contrast,others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy.CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment.CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.展开更多
Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated c...Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.展开更多
Rosa canina is a member of the genus Rosa that has long been used for medical objectives. Several studies have reported cytotoxic effects of different Rosa species, but there has been only limited investigation of the...Rosa canina is a member of the genus Rosa that has long been used for medical objectives. Several studies have reported cytotoxic effects of different Rosa species, but there has been only limited investigation of the cytotoxic effect of R. canina. The purpose of the current study was to examine the potential effect of R.canina extract on cell viability, the cell cycle, apoptosis, and the expression of telomerase in human colon cancer(WiDr) cells. The cytotoxic effect of the extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of the extract was then evaluated in terms of apoptosis and the cell cycle using flow cytometry. Mitochondrial membrane potential(MMP) was investigated using the fluorometric method, and expression levels of telomerase were studied using RT-PCR. R. canina extract exhibited a selective cytotoxic effect on WiDr cells compared with normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. R. canina extract significantly repressed telomerase expressions at treatment times of 48 and 72 h in WiDr cells. Our results suggest that R. canina may have considerable potential for development as a novel natural product-based anticancer agent.展开更多
Objective:The current study investigated the efficacy of total ethanolic extract and various fractions of Gazania rigens to protect against carbon tetrachloride-induced liver and kidney damage in rats and evaluated th...Objective:The current study investigated the efficacy of total ethanolic extract and various fractions of Gazania rigens to protect against carbon tetrachloride-induced liver and kidney damage in rats and evaluated their antioxidant activity.Methods:The antioxidant activity of the total extract and fractions(petroleum ether,ethyl acetate,and aqueous)of Gazania rigens was examined using 2,2’-diphenyl-1-picrylhydrazyl radical scavenging and phosphomolybdate assays,and their total phenolic and flavonoid contents were determined.The hepatoprotective and nephroprotective potentials were studied at a dose of 300 mg/kg for six consecutive days followed by induction of hepatorenal injury using carbon tetrachloride single dose(1.5 mL/kg,1:1 v/v in olive oil,intraperitoneal)the next day.Results:The results revealed the potent hepato and nephroprotective effects of ethyl acetate and aqueous fractions by significantly(P<0.01 or P<0.001)reducing the serum levels of alanine aminotransferase,aspartate aminotransferase,total bilirubin,creatinine,urea,triglycerides,cholesterol,and lactate dehydrogenase,along with elevated serum albumin levels.The improvement of hepatic and renal antioxidant capacities and catalase activities,together with the prominent reduction of hepatic and renal malondialdehyde contents,were confirmed by histopathological examination.Conclusion:The potent hepatoprotective and nephroprotective effects of the total extract and different fractions of Gazania rigens may be attributed to the presence of highly phenolic and flavonoid compounds along with their complementary antioxidant scavenging properties.展开更多
Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individua...Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals.The primary treatment is either supportive or symptomatic.Natural products have an important role in the development of various drugs.Thus,screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses.In the current study,an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents,(e.g.,procyanidin B2,theaflavin,quercetin,ellagic acid,caffeoylquinic acid derivatives,berginin,eudesm-1β,6α,11-triol and arbutin),on the crystal structure of SARS-CoV-2 main protease(PDB ID:6w63)using AutoDock-Vina software.Many of the docked compounds revealed good binding affinity,with procyanidin B2(–8.6 Kcal/mol)and theaflavin(–8.5 Kcal/mol)showing a better or similar binding score as the ligand(–8.5 Kcal/mol).Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin.Procyanidin B2,theaflavin,and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways.Additionally,these phytoconstituents showed good ADME properties and acceptable lipophilicity,as evaluated using WLOGP.Amongst the tested compounds,procyanidin B2 showed the highest lipophilic value.It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.展开更多
6-aminouracil 1 was utilized to introduce different heterocyclic rings at C-6 position through various synthetic strategies. The synthesized compounds bear rings that are either directly attached to the uracil back bo...6-aminouracil 1 was utilized to introduce different heterocyclic rings at C-6 position through various synthetic strategies. The synthesized compounds bear rings that are either directly attached to the uracil back bone as in compounds 6, 12a-c and 15, or attached through an amino bridge as compounds 3a-c, 5a, b, 7a, b, 9 and 10, or through an imino bridge as compound 18. Also, compounds 4, 8, 11a-c, 14, 16 and 17 bearing biologically active side chains were synthesized. In addition to, compounds 13, 19, 20, 21 and 22 bear fused rings to the uracil backbone. All synthesized compounds were evaluated for their anticancer activity against prostate PC3 cell line using in-vitro sulforhodamine-B (SRB) method, from which compounds 3a, c, 4, 5a, b, 6, 7a, b, 11a-c, 12a, b, 17 and 20 were the most active. These active compounds were further evaluated for their ability to inhibit cathepsin B enzyme by using enzyme-linked immunosorbent assay, which revealed that compounds 5a, b, 7a, 11a, 12a and 17 exhibited more than 50% inhibition of cathepsin B. Among which the phenyl thiourea derivative 17 was the most active exhibiting 82.3% inhibition, while the reference doxorubicin exerted 18.7% inhibition.展开更多
Hairdressers are chronically exposed to several occupational hazards during their work including potentially genotoxic chemicals. Hair dying, hair smoothening and straightening products are hazardous chemicals that af...Hairdressers are chronically exposed to several occupational hazards during their work including potentially genotoxic chemicals. Hair dying, hair smoothening and straightening products are hazardous chemicals that affect human health and are frequently used in beauty salons. So, this study aimed to evaluate the genotoxic risk among the studied hairdressers, to estimate the level of p-phenylenediamine (p-PDA) in urine and to assess the degree of adherence of the studied hair- dressers to occupational safety measures at work. A comparative cross sectional study was carried out on 40 hairdressers working in beauty salons in Zagazig city, Egypt and 40 administrative staff at faculty of medicine as a control group. The results of the study revealed a significant increase in mean concentration of urinary p-PDA as well as significant increase in DNA damage assessed by Comet assay in lymphocytes among studied hairdressers than among their controls. Also, there was a statistically significant decrease in adherence to most of the occupational safety precaution measures that should be followed by the studied hairdressers. The significant risk factors of high Comet total mean score among the studied hairdressers were occupational use of hair straightening ≥8 times/week, use of hair dyes at work ≥15 times/week, length of service ≥13 years, negligence of wearing gloves during work, use of bleaching agents ≥12/week and negligence of hand wash after handling chemicals. So, it was concluded that the hairdressers are occupationally exposed to the risk of genotoxic hazards from chemicals frequently used in their work. The lack of commitment to occupational safety measures at beauty salons like wearing gloves during work and hand washing increases the risk of genotoxicity.展开更多
Many countries in the world wide banned hydroquinone in cosmetics skin lightening but it is still used in most of Africa countries, including Sudan. Few studies were carried out on the side effect of hydroquinone on S...Many countries in the world wide banned hydroquinone in cosmetics skin lightening but it is still used in most of Africa countries, including Sudan. Few studies were carried out on the side effect of hydroquinone on Sudanese women. Therefore, the present study was carried out in Khartoum state in April to May/2014 to assess the awareness of Sudanese women about using hydroquinone and its probable risks. The results revealed that, highly using cosmetics containing hydroquinone by women aged between 20 - 29 years (78.3%) as well as by those classified as single (69.6%). The results also showed that the highest percentage of women was using it during evening (81.2%) and a high percentage of them was using it for skin lightening (65.2%), followed by elimination acne (20.3%) and about 10.1% for both skin lightening and elimination of acne and very little (4.3%) for freckle elimination. Moreover, the results showed a very high percentage of women (94.2%) used the chemical without being prescribed by doctors and about (85.5%) of them didn’t know its nature and risks on human health. Consequently, (50.7%) of women have had sides effects, (44.9 %) used more than one and (44.1%) used it regularly. In addition, the results revealed that a wide range of products of this chemical was available in local market with amalico (34.8%) being highly used. The study can conclude that the awareness of Sudanese women about this compound was poor and needs to be raised by health authorities.展开更多
Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in di...Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.展开更多
Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplasti...Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.展开更多
The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the tra...The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the transcriptome and the epigenome, besides enabling genome-wide assessment of genetic variations. With the advent of new drugs that are indicated tissue agnostic, depending on certain mutations, there is a growing demand for fast and cost-effective genetic diagnosis. The method in focus that already became an indispensable tool in viral diagnosis is next-generation sequencing (NGS). This approach allows sequencing of literally every DNA molecule in the sample and can either be used to assess numerous genetic markers of one patient at a time, or to assess fewer markers of many patients in parallel, which reduces costs. We submitted 23 samples of different tumor entities to four diagnostic companies with different analysis profiles. The results as disclosed and discussed in this report indicate that so far, the main application of NGS is rather in cancer research than in diagnosis, as none of the reports had a real impact on the therapeutic scheme. We are perfectly aware that such a small cohort cannot be generalized, but considering the costs vs. benefits, NGS should be engaged upon a very stringent evaluation only. However, in cases where obtaining a tissue biopsy is impossible or unfavorable, analysis of liquid biopsy by NGS provides a vital alternative.展开更多
The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The ...The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.展开更多
Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral ...Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral hypoglycemic drug for controlling type 2 DM(T2DM)patients.Metformin is the ninth most often prescribed drug in the world,and at least 120 million diabetic people are estimated to receive the drug.In the last 20 years,there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients.Many studies have reported that vitamin B12 deficiency is related to the malabsorption of vitamin B12 among metformin-treated T2DM patients.Vitamin B12 deficiency may have a very bad complication for the T2DM patient.In this review,we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption.In addition,the review will describe the clinical outcomes of vitamin B12 deficiency in metformintreated T2DM.展开更多
文摘AIM： To investigate the role of oxidative injury in pancreatitis-induced hepatic damage and the effect of antioxidant agents such as melatonin, ascorbic acid and N-acetyl cysteine on caerulein-induced pancreatitis and associated liver injury in rats. METHODS： Thirty-eight female Wistar rats were used. Acute pancreatitis （AP） was induced by two i.p. injections of caerulein at 2-h intervals （at a total dose of 100 μg/kg b.wt）. The other two groups received additional melatonin （20 mg/kg b.wt） or an antioxidant mixture containing L（＋）-ascorbic acid （14.3 mg/kb.wt.） and N-acetyl cysteine （181 mg/kg b.wt.） i.p. shortly before each injection of caerulein. The rats were sacrificed by decapitation 12 h after the last injection of caerulein. Pancreatic and hepatic oxidative stress markers were evaluated by changes in the amount of lipid peroxides measured as malondialdehyde （MDA） and changes in tissue antioxidant enzyme levels, catalase （CAT） and glutathione peroxidase （GPx）. Histopathological examination was performed using scoring systems. RESULTS： The degree of hepatic cell degeneration, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration showed a significant difference between caerulein and caerulein＋melatonin （P= 0.001）, and careulein and caerulein ＋ L（＋）- ascorbic acid ＋N-acetyl cysteine groups （P= 0.002）. The degree of aciner cell degeneration, pancreatic edema, intracellular vacuolization and inflammatory infiltration showed a significant difference between caerulein and caerulein ＋ melatonin （P=0.004）, and careulein and caerulein ＋ L（＋）-ascorbic acid ＋N-acetyl cysteine groups （P=0.002）. Caerulein-induced pancreatic and liver damage was accompanied with a significant increase in tissue MDA levels （P= 0.01, P= 0.003, respectively） whereas a significant decrease in CAT （P= 0.002, P=0.003, respectively） and GPx activities （P= 0.002, P= 0.03, respectively）. Melatonin and L（＋）-ascorbic acid ＋N-acetyl cysteine administration significantly decreased MDA levels in pancreas （P= 0.03, P= 0.002, respectively） and liver （P= 0.007, P= 0.01, respectively）. Administration of these agents increased pancreatic and hepatic CAT and GPx activities. Melatonin significantly increased pancreatic and hepatic CAT （P= 0.002, P= 0.001, respectively） and GPx activities （P=0.002, P=0.001）. Additionally, L（＋）-ascorbic acid＋N-acetyl cysteine significantly increased pancreatic GPx （P= 0.002） and hepatic CAT and GPx activities （P= 0.001, P= 0.007, respectively） CONCLUSION： Oxidative injury plays an important role not only in the pathogenesis of AP but also in pancreatitis-induced hepatic damage. Antioxidant agents such as melatonin and ascorbic acid＋N-acetyl cysteine, are capable of limiting pancreatic and hepatic damage produced during AP via restoring tissue antioxidant enzyme activities.
基金funded by the Research Fund of Ege University,Project No. 05/ECZ/020
文摘Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antJoxJdant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide ＋ resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.
文摘Obesity is a major and growing health care concern. Large epidemiologic studies that evaluated the relationship between obesity and mortality, observed that a higher body-mass index(BMI) is associated with increased rate of death from several causes, among them cardiovascular disease; which is particularly true for those with morbid obesity. Being overweight was also associated with decreased survival in several studies. Unfortunately, obese subjects are often exposed to public disapproval because of their fatness which significantly affects their psychosocial behavior. All obese patients(BMI ≥ 30 kg/m2) should receive counseling on diet, lifestyle, exercise and goals for weight management. Individuals with BMI ≥ 40 kg/m2 and those with BMI > 35 kg/m2 with obesity-related comorbidities; who failed diet, exercise, and drug therapy, should be considered for bariatric surgery. In current review article, we will shed light on important medical principles that each surgeon/gastroenterologist needs to know about bariatric surgical procedure, with special concern to the early post operative period. Additionally, we will explain the common complications that usually follow bariatric surgery and elucidate medical guidelines in their management. For the first 24 h after the bariatric surgery, the postoperative priorities include pain management, leakage, nausea and vomiting, intravenous fluid management, pulmonary hygiene, and ambulation. Patients maintain a low calorie liquid diet for the first few postoperative days that is gradually changed to soft solid food diet within two or three weeks following the bariatric surgery. Later, patients should be monitored for postoperative complications. Hypertension, diabetes, dumping syndrome, gastrointestinal and psychosomatic disorders are among the most important medical conditions discussed in this review.
文摘AIM: To evaluate the protective effect of diallyl sulfide (DAS) against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis.METHODS: Male Wistar rats received either NDEA or NDEA together with DAS as protection.Liver energy metabolism was assessed in terms of lactate,pyruvate,lactate/pyruvate,ATP levels,lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD) activities.In addition,membrane disintegration of the liver cells was evaluated by measuring lipid-peroxidation products,measured as malondialdehyde (MDA); nitric oxide (NO) levels; glucose-6-phosphatase (G6Pase),catalase (CAT) and superoxide dismutase (SOD) activities.Liver DNA level,glutathione-S-transferase (GST) and cytochrome c oxidase activities were used as DNA fragmentation indices.Aldose reductase (AR) activity was measured as an index for cancer cells resistant to chemotherapy and histopathological examination was performed on liver sections from different groups.RESULTS: NDEA significantly disturbed liver functions and most of the aforementioned indices.Treatment with DAS significantly restored liver functions and hepatocellular integrity; improved parameters of energy metabolism and suppressed free-radical generation.CONCLUSION: We provide evidence that DAS exerts a protective role on liver functions and tissue integrity in face of enhanced tumorigenesis caused by NDEA,as well as improving cancer-cell sensitivity to chemotherapy.This is mediated through combating oxidative stress of free radicals,improving the energy metabolic state of the cell,and enhancing the activity of G6Pase,GST and AR enzymes.
文摘Objective:To identify unique immunogenic epitopes of Zika virus non-structural 1(NS1)antigen and produce immunoglobulin Y(IgY)for potential use in he diagnosis of of Zika virus infection.Methods:Immunogenic epitopes were identified using in silico B-cell epitope prediction.A synthetic peptide analog of the predicted epitope was used to induce antipeptide IgY production in hens which was purified using affinity chromatography.Presence of purified IgY and its binding specificity were performed by gel electrophoresis and ELISA,respectively.Results:Out of the nine continuous epitopes identified,the sequence at position 193-208(LKVREDYSLECDPAVI)was selected and used to produce anti-peptide IgY.The produced IgY was found to bind to the synthetic analog of the Zika virus NS1 immunogenic epitope but not to other flaviviruses and random peptides from other pathogens.Conclusions:In this study,we identified an immunogenic epitope unique to Zika virus that can be used to develop a serodiagnostic tool that specifically detect Zika virus infection.
文摘Determination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved.Adipose-derived mesenchymal stem cells(AD-MSC)are easily isolated and cultured for a long time before losing their stem cell characteristics,which are self-renewal and pluripotency.AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics.They are easily accessible,and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells.It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression.These advantages have popularized its use in many fields including plastic reconstructive surgery.However,in the field of hepatology and liver transplantation,the progress is slower.AD-MSC have the potential to modulate inflammation,ameliorate ischemia-reperfusion injury,and support liver and biliary tract regeneration.These are very important for the treatment of various hepatobiliary diseases.Furthermore,the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis.We need alternative therapeutic approaches to treat end-stage liver failure.AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation.Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.
基金Supported by Deanship of scientific research,King Faisal University,KSA(Grant no.170323-2012)
文摘Objective:To clarify the modulatory effects of daily consumption of pomegranate extract(PE),olive oil(OO)andNagilla sativaoil(NSO)on antioxidant activity,sperm quality and pituitary-testicular axis of adult male wistar rats.Methods:Thirty-two adult male Wistar rats were dividedinto four equal groups,eight rats each.Using rat gastric tubes,1.0 mL distilled water,1.0 mL PE,0.4mL NSO and 0.4 mL OO were orally administered daily for 6 weeks in the first,second,third andfourth groups,respectively.Reproductive organs,body weight,sperm criteria,testosterone,FSH,LH,inhibin-B,lipid peroxidation,and antioxidant enzyme activities were investigated.At the endof the study protocol,analyses occurred at the same time.Data were analysed by ANOVA test and P<0.05 was considered to be a significant value.Results:In all studied groups,malondialdehydelevel was significantly decreased accompanied with an increases in glutathione peroxidase andglutathione.Rats treated with PE showed an increase in catalase activities accompanied withan increase in sperm concentration which was also observed in NSO group.In PE treated group,sperm motility was also increased accompanied with decreased abnormal sperm rate.NSO,OOand PE treated groups shows an insignificant effect on testosterone,inhibin-B,FSH and LH incomparison with control group.Conclusions:These results show that administration of PE,NSOand OO could modify sperm characteristics and antioxidant activity of adult male wistar rats.
文摘Breast cancer(BC)is the most common heterogeneous disease in women and one of the leading causes of cancer-related death.Surgery,chemotherapy,radiotherapy,hormone,and targeted therapy are the gold standards for BC treatment.One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics,resistance that severely limits the use and effectiveness of the drugs used for BC treatment.Therefore,it is essential to develop new strategies to improve therapeutic efficacy.Circular RNAs(circRNAs)are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′,and 3′;ends.Accumulating evidence suggests that circRNAs have a vital role in cancer development,progression,and BC resistance to chemotherapy.The purpose of this review is to discuss the biological properties of circRNAs,and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment,by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance,such as drug efflux,apoptosis dysfunction,autophagy,and DNA damage repair.CircRNAs are associated with drug resistance via ATP-binding cassette(ABC)efflux transporters,while some others by inhibition of cell apoptosis,thus leading to resistance to tamoxifen in BC cells.In contrast,others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy.CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment.CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.
文摘Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.
基金the Foundation of Scientific Research of Gumushane University for financially supporting this research under Project No: 13.F5119.02.1
文摘Rosa canina is a member of the genus Rosa that has long been used for medical objectives. Several studies have reported cytotoxic effects of different Rosa species, but there has been only limited investigation of the cytotoxic effect of R. canina. The purpose of the current study was to examine the potential effect of R.canina extract on cell viability, the cell cycle, apoptosis, and the expression of telomerase in human colon cancer(WiDr) cells. The cytotoxic effect of the extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of the extract was then evaluated in terms of apoptosis and the cell cycle using flow cytometry. Mitochondrial membrane potential(MMP) was investigated using the fluorometric method, and expression levels of telomerase were studied using RT-PCR. R. canina extract exhibited a selective cytotoxic effect on WiDr cells compared with normal colon cells. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in WiDr cells. R. canina extract significantly repressed telomerase expressions at treatment times of 48 and 72 h in WiDr cells. Our results suggest that R. canina may have considerable potential for development as a novel natural product-based anticancer agent.
文摘Objective:The current study investigated the efficacy of total ethanolic extract and various fractions of Gazania rigens to protect against carbon tetrachloride-induced liver and kidney damage in rats and evaluated their antioxidant activity.Methods:The antioxidant activity of the total extract and fractions(petroleum ether,ethyl acetate,and aqueous)of Gazania rigens was examined using 2,2’-diphenyl-1-picrylhydrazyl radical scavenging and phosphomolybdate assays,and their total phenolic and flavonoid contents were determined.The hepatoprotective and nephroprotective potentials were studied at a dose of 300 mg/kg for six consecutive days followed by induction of hepatorenal injury using carbon tetrachloride single dose(1.5 mL/kg,1:1 v/v in olive oil,intraperitoneal)the next day.Results:The results revealed the potent hepato and nephroprotective effects of ethyl acetate and aqueous fractions by significantly(P<0.01 or P<0.001)reducing the serum levels of alanine aminotransferase,aspartate aminotransferase,total bilirubin,creatinine,urea,triglycerides,cholesterol,and lactate dehydrogenase,along with elevated serum albumin levels.The improvement of hepatic and renal antioxidant capacities and catalase activities,together with the prominent reduction of hepatic and renal malondialdehyde contents,were confirmed by histopathological examination.Conclusion:The potent hepatoprotective and nephroprotective effects of the total extract and different fractions of Gazania rigens may be attributed to the presence of highly phenolic and flavonoid compounds along with their complementary antioxidant scavenging properties.
文摘Coronaviruses caused an outbreak pandemic disease characterized by a severe acute respiratory distress syndrome leading to the infection of more than 200 million patients and the death of more than 4 million individuals.The primary treatment is either supportive or symptomatic.Natural products have an important role in the development of various drugs.Thus,screening of natural compounds with reported antiviral activities can lead to the discovery of potential inhibitory entities against coronaviruses.In the current study,an in-silico molecular docking experiment was conducted on the effects of some of these natural antiviral phytoconstituents,(e.g.,procyanidin B2,theaflavin,quercetin,ellagic acid,caffeoylquinic acid derivatives,berginin,eudesm-1β,6α,11-triol and arbutin),on the crystal structure of SARS-CoV-2 main protease(PDB ID:6w63)using AutoDock-Vina software.Many of the docked compounds revealed good binding affinity,with procyanidin B2(–8.6 Kcal/mol)and theaflavin(–8.5 Kcal/mol)showing a better or similar binding score as the ligand(–8.5 Kcal/mol).Molecular dynamics simulations were carried out at 100 ns and revealed that procyanidin B2 forms a more stable complex with SARS-CoV-2 main protease than theaflavin.Procyanidin B2,theaflavin,and 4,5-dicaffeoylquinic acid were evaluated for toxicity by ProTox-II webserver and were non-toxic according to the predicted LD50 values and safe on different organs and pathways.Additionally,these phytoconstituents showed good ADME properties and acceptable lipophilicity,as evaluated using WLOGP.Amongst the tested compounds,procyanidin B2 showed the highest lipophilic value.It is worth mentioning that these natural inhibitiors of SARS-CoV-2 main protease are components of green and black tea that can be used as a supporting supplement for COVID patients or as potential nuclei for further drug design and development campaigns.
文摘6-aminouracil 1 was utilized to introduce different heterocyclic rings at C-6 position through various synthetic strategies. The synthesized compounds bear rings that are either directly attached to the uracil back bone as in compounds 6, 12a-c and 15, or attached through an amino bridge as compounds 3a-c, 5a, b, 7a, b, 9 and 10, or through an imino bridge as compound 18. Also, compounds 4, 8, 11a-c, 14, 16 and 17 bearing biologically active side chains were synthesized. In addition to, compounds 13, 19, 20, 21 and 22 bear fused rings to the uracil backbone. All synthesized compounds were evaluated for their anticancer activity against prostate PC3 cell line using in-vitro sulforhodamine-B (SRB) method, from which compounds 3a, c, 4, 5a, b, 6, 7a, b, 11a-c, 12a, b, 17 and 20 were the most active. These active compounds were further evaluated for their ability to inhibit cathepsin B enzyme by using enzyme-linked immunosorbent assay, which revealed that compounds 5a, b, 7a, 11a, 12a and 17 exhibited more than 50% inhibition of cathepsin B. Among which the phenyl thiourea derivative 17 was the most active exhibiting 82.3% inhibition, while the reference doxorubicin exerted 18.7% inhibition.
文摘Hairdressers are chronically exposed to several occupational hazards during their work including potentially genotoxic chemicals. Hair dying, hair smoothening and straightening products are hazardous chemicals that affect human health and are frequently used in beauty salons. So, this study aimed to evaluate the genotoxic risk among the studied hairdressers, to estimate the level of p-phenylenediamine (p-PDA) in urine and to assess the degree of adherence of the studied hair- dressers to occupational safety measures at work. A comparative cross sectional study was carried out on 40 hairdressers working in beauty salons in Zagazig city, Egypt and 40 administrative staff at faculty of medicine as a control group. The results of the study revealed a significant increase in mean concentration of urinary p-PDA as well as significant increase in DNA damage assessed by Comet assay in lymphocytes among studied hairdressers than among their controls. Also, there was a statistically significant decrease in adherence to most of the occupational safety precaution measures that should be followed by the studied hairdressers. The significant risk factors of high Comet total mean score among the studied hairdressers were occupational use of hair straightening ≥8 times/week, use of hair dyes at work ≥15 times/week, length of service ≥13 years, negligence of wearing gloves during work, use of bleaching agents ≥12/week and negligence of hand wash after handling chemicals. So, it was concluded that the hairdressers are occupationally exposed to the risk of genotoxic hazards from chemicals frequently used in their work. The lack of commitment to occupational safety measures at beauty salons like wearing gloves during work and hand washing increases the risk of genotoxicity.
文摘Many countries in the world wide banned hydroquinone in cosmetics skin lightening but it is still used in most of Africa countries, including Sudan. Few studies were carried out on the side effect of hydroquinone on Sudanese women. Therefore, the present study was carried out in Khartoum state in April to May/2014 to assess the awareness of Sudanese women about using hydroquinone and its probable risks. The results revealed that, highly using cosmetics containing hydroquinone by women aged between 20 - 29 years (78.3%) as well as by those classified as single (69.6%). The results also showed that the highest percentage of women was using it during evening (81.2%) and a high percentage of them was using it for skin lightening (65.2%), followed by elimination acne (20.3%) and about 10.1% for both skin lightening and elimination of acne and very little (4.3%) for freckle elimination. Moreover, the results showed a very high percentage of women (94.2%) used the chemical without being prescribed by doctors and about (85.5%) of them didn’t know its nature and risks on human health. Consequently, (50.7%) of women have had sides effects, (44.9 %) used more than one and (44.1%) used it regularly. In addition, the results revealed that a wide range of products of this chemical was available in local market with amalico (34.8%) being highly used. The study can conclude that the awareness of Sudanese women about this compound was poor and needs to be raised by health authorities.
基金supported by1R01EY030054(MA),NIH-1R01EY029751(AT)supported in part by National Center for Research Resources,National Institutes of Health Grant S10RR027926.
文摘Hyperhomocysteinemia(HHcy)contributes to the incidence of many cardiovascular diseases(CVD).Our group have previously established crucial roles of eicosanoids and homocysteine in the incidence of vascular injury in diabetic retinopathy and renal injury.Using cystathionine-β-synthase heterozygous mice(cβs^(+/-))as a model of HHcy,the current study was designed to determine the impact of homocysteine on circulating levels of lipid mediators derived from polyunsaturated fatty acids(PUFA).Plasma samples were isolated from wild-type(WT)and cβs^(+/-)mice for the assessment of eicosanoids levels using LC/MS.Plasma 12/15-lipoxygenase(12/15-LOX)activity significantly decreased in cβs^(+/-)vs.WT control mice.LOX-derived metabolites from both omega-3 and omega-6 PUFA were also reduced in cβs^(+/-)mice compared to WT control(P<0.05).Contrary to LOX metabolites,cytochrome P450(CYP)metabolites from omega-3 and omega-6 PUFA were significantly elevated in cβs^(+/-)mice compared to WT control.Epoxyeicosatrienoic acids(EETs)are epoxides derived from arachidonic acid(AA)metabolism by CYP with anti-inflammatory properties and are known to limit vascular injury,however their physiological role is limited by their rapid degradation by soluble epoxide hydrolase(sEH)to their corresponding diols(DiHETrEs).In cβs^(+/-)mice,a significant decrease in the plasma EETs bioavailability was obvious as evident by the decrease in EETs/DiHETrEs ratio relative to WT control mice.Cyclooxygenase(COX)metabolites were also significantly decreased in cβs^(+/-)vs.WT control mice.These data suggest that HHcy impacts eicosanoids metabolism through decreasing LOX and COX metabolic activities while increasing CYP metabolic activity.The increase in AA metabolism by CYP was also associated with increase in sEH activity and decrease in EETs bioavailability.Dysregulation of eicosanoids metabolism could be a contributing factor to the incidence and progression of HHcy-induced CVD.
文摘Oxidative stress is involved in chronic and acute pathologies: cardiovascular, neurodegenerative, neoplastic, inflammatory and infectious diseases. Clinical trials focused on prevention of cardiovascular and neoplastic diseases involving antioxidant supplementation have however provided predominantly negative obserations in large-scale studies. Screening of patient cohorts to assess baseline oxidative stress on the basis of a biomarker profile is decisive but lacking. For the first time, we evaluated the level of oxidative stress, testing more than 10 established biomarkers, in a comprehensive initial survey of 617 patients displaying chronic human pathologies. Multiple diseasespecific abnormalities were identified in plasma, whole blood and/or urine. This is the case for vitamins and oligo elements, vitamin C, vitamin E, β-carotene, selenium, zinc and copper;endogenous antioxidants such as reduced and oxidised glutathione, thiols, urate, and glutathione peroxidase activity, and a biomarker of oxidative DNA damage (8-hydroxy-2’-deoxy guanosine). The distinct biomarker profiles suggest the involvment of multiple forms of oxidative insults which arein some way partially specific to each pathological condition. This finding is in favor of the determination of an integrated score to combine contributions of distinct biomarkers, in order to screen patients presenting elevated levels of oxidative stress.
文摘The understanding of how genetic and epigenetic factors influence tumorigenesis, progression and invasion, is vastly growing since new technologies allow the analysis of the functional genome namely the exome, the transcriptome and the epigenome, besides enabling genome-wide assessment of genetic variations. With the advent of new drugs that are indicated tissue agnostic, depending on certain mutations, there is a growing demand for fast and cost-effective genetic diagnosis. The method in focus that already became an indispensable tool in viral diagnosis is next-generation sequencing (NGS). This approach allows sequencing of literally every DNA molecule in the sample and can either be used to assess numerous genetic markers of one patient at a time, or to assess fewer markers of many patients in parallel, which reduces costs. We submitted 23 samples of different tumor entities to four diagnostic companies with different analysis profiles. The results as disclosed and discussed in this report indicate that so far, the main application of NGS is rather in cancer research than in diagnosis, as none of the reports had a real impact on the therapeutic scheme. We are perfectly aware that such a small cohort cannot be generalized, but considering the costs vs. benefits, NGS should be engaged upon a very stringent evaluation only. However, in cases where obtaining a tissue biopsy is impossible or unfavorable, analysis of liquid biopsy by NGS provides a vital alternative.
文摘The coronavirus disease 2019(COVID-19)represents a global health and economic challenge.Hepatic injuries have been approved to be associated with severe acute respiratory syndrome coronavirus(SARS-CoV-2)infection.The viral tropism pattern of SARS-CoV-2 can induce hepatic injuries either by itself or by worsening the conditions of patients with hepatic diseases.Besides,other factors have been reported to play a crucial role in the pathological forms of hepatic injuries induced by SARS-CoV-2,including cytokine storm,hypoxia,endothelial cells,and even some treatments for COVID-19.On the other hand,several groups of people could be at risk of hepatic COVID-19 complications,such as pregnant women and neonates.The present review outlines and discusses the interplay between SARS-CoV-2 infection and hepatic injury,hepatic illness comorbidity,and risk factors.Besides,it is focused on the vaccination process and the role of developed vac-cines in preventing hepatic injuries due to SARS-CoV-2 infection.
文摘Diabetes mellitus(DM)is still one of the most common diseases worldwide,and its prevalence is still increasing globally.According to the American and European recommendations,metformin is considered a first-line oral hypoglycemic drug for controlling type 2 DM(T2DM)patients.Metformin is the ninth most often prescribed drug in the world,and at least 120 million diabetic people are estimated to receive the drug.In the last 20 years,there has been increasing evidence of vitamin B12 deficiency among metformin-treated diabetic patients.Many studies have reported that vitamin B12 deficiency is related to the malabsorption of vitamin B12 among metformin-treated T2DM patients.Vitamin B12 deficiency may have a very bad complication for the T2DM patient.In this review,we will focus on the effect of metformin on the absorption of vitamin B12 and on its proposed mechanisms in hindering vitamin B12 absorption.In addition,the review will describe the clinical outcomes of vitamin B12 deficiency in metformintreated T2DM.
