Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Targeted anti-tumor synergistic effects of Myc decoy oligodeoxynucleotides-loaded selenium nanostructure combined with chemoradiotherapy on LNCaP prostate cancer cells

In the present study,we investigated the synergistic effects of targeted methotrexate-selenium nanostructure containing Myc decoy oligodeoxynucleotides along with X-irradiation exposure as a combination therapy on LNCaP prostate cancer cells.Myc decoy ODNs were designed based on the promoter of Bcl-2 gene and analyzed by molecular docking and molecular dynamics assays.ODNs were loaded on the synthesized Se@BSA@Chi-MTX nanostructure.The physicochemical characteristics of nanostructures were determined by FTIR,DLS,UV-vis,TEM,EDX,in vitro release,and hemolysis tests.Subsequently,the cytotoxicity properties of them with and without X-irradiation were investigated by uptake,MTT,cell cycle,apoptosis,and scratch assays on the LNCaP cell line.The results of DLS and TEM showed negative charge(−9 mV)and nanometer size(40 nm)for Se@BSA@Chi-DEC-MTX NPs,respectively.The results of FTIR,UV-vis,and EDX showed the proper interaction of different parts and the correct synthesis of nanoparticles.The results of hemolysis showed the hemocompatibility of this nanoparticle in concentrations less than 6 mg/mL.The ODNs release from the nanostructures showed a pH-dependent manner,and the release rate was 15%higher in acidic pH.The targeted Se@BSA@Chi-labeled ODN-MTX NPs were efficiently taken up by LNCaP cells by targeting the prostate-specific membrane antigen(PSMA).The significant synergistic effects of nanostructure(containing MTX drug)treatment along with X-irradiation showed cell growth inhibition,apoptosis induction(~57%),cell cycle arrest(G2/M phase),and migration inhibition(up to 90%)compared to the control.The results suggested that the Se@BSA@Chi-DEC-MTX NPs can potentially suppress the cell growth of LNCaP cells.This nanostructure system can be a promising approach for targeted drug delivery and chemoradiotherapy in prostate cancer treatment.

Isoimperatorin alleviates acetic acid-induced colitis in rats

Objective:To investigate the effect of isoimperatorin on histopathological and biochemical changes in acetic acid-induced colitis rats.Methods:Colitis was induced by intracolonic administration of acetic acid solution(4%v/v)in rats.Rats were divided into six groups including the sham group,the negative control group,the dexamethasone-treated group,and the groups treated with isoimperatorin(0.1,1,and 10 mg/kg/d by gavage).The treatments were administered for three days and then colonic status was assessed by macroscopic,histopathological,and biochemical analyses.Results:Isoimperatorin significantly alleviated colonic damage in a dose-dependent manner and improved histological changes in rats with acetic acid-induced colitis.It also significantly reduced myeloperoxidase,TNF-α,IL-1β,and malodialdehyde levels.Conclusions:Isoimperatorin alleviates acetic acid-induced colitis in rats and may be a potential therapeutic agent for the treatment of colitis.

Analytical methodologies for determination of methotrexate and its metabolites in pharmaceutical,biological and environmental samples

Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.

Biopharmaceuticals for prevention of COVID-19:A scoping review

The COVID-19 epidemic caused by SARS-CoV-2 virus has turned into a worldwide pandemic.Therefore,health officials all around the world have strived for developing efficient preventive and treatment methods to deal with this global crisis.Amongst them,monoclonal antibodies,anti-TNFs,and convalescent plasma appear to be effective against this disease.In addition,clinical trials are currently being conducted for viral targeting vaccines.This review summarizes major advances using biopharmaceuticals in the treatment and prevention strategies against COVID-19 that have occurred in the global medicinal system from its introduction until March 2022.

Cardioprotective effects of Pinus eldarica bark extract on adrenaline-induced myocardial infarction in rats

Objective:To investigate the effect of Pinus eldarica bark extract on adrenaline-induced myocardial infarction.Methods:Hydroalcoholic extract was prepared using maceration method and its total phenolic content was determined using the Folin-ciocalteu method.Pretreatment was done by oral administration of 100,200,and 400 mg/kg Pinus eldarica bark extract for 16 days in male Wistar rats.Injection of adrenaline(2 mg/kg,s.c.)was performed on the 15th and 16th days for induction of myocardial infarction.LeadⅡEEG was recorded.Serum cardiac marker enzymes and antioxidative parameters were evaluated and a histopathological examination of heart tissues was performed.Results:Pretreatment with Pinus eldarica bark extract especially at its high doses significantly lowered the ST-segment elevation,improved heart rate,and decreased RR interval in ECG pattern of rats with adrenaline-induced myocardial infarction.It declined serum markers of heart damage including aspartate aminotransferase,lactate dehydrogenase,and creatine phosphokinase-MB,and also decreased lipid peroxidation marker,and heart weight while raising total antioxidant capacity and considerably improved histopathological alterations of the heart induced by adrenaline.Conclusions:Pinus eldarica bark extract shows beneficial cardioprotective and antioxidant effects against adrenaline-induced myocardial infarction.It can be further explored as a potential treatment for myocardial infarction.

Effect of heparin on recurrent IVF-ET failure patients

Objective:To elucidate the possible role of unfractionated heparin in patients with failed repeated in in vitro fertilization and embryo transfer(IVF-ET)and thrombophilia.Methods:This case control study evaluated the efficacy of the unfractionated heparin in increasing the pregnancy and implantation ratio in women with recurrent IVF-ET failures.Eighty-six women received in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)with a record of three or more previous IVF-ET failures.Participants were randomly distributed into two groups.Group A(n=43)received unfractionated heparin 5000 IU twice daily,and group B(n=43)did not take any antithrombotic drugs.Coagulation abnormalities such as factor桋Leiden(FVL)mutation,methylene tetra hydro folate reductase(MTHFR)mutation and prothrombin mutation(F栻)were evaluated.Age,body mass index,basal follicular stimulating hormone,basal estradiol,duration of infertility,and number of IVF-ET failures were compared between two groups.Results:45.0%and 17.4%of women were pregnant with and without MTHFR and prothrombin mutation,respectively,when they received unfractionated heparin treatment.The implantation rate was more in group A(12.5%)than group B(4.3%)and differences in the fertilization rate of the two groups were observed(27.7%vs.35.9%).The clinical pregnancy rate per cycle was remarkably more in group A(30.2%)than group B(14.0%).Conclusions:Heparin is a safe and valuable treatment for patients with repeated IVF-ET failures.The clinical pregnancy and implantation rates are higher in the heparin-treated group in contrast with the control group.

Effectiveness of probiotics in irritable bowel syndrome:Updated systematic review with meta-analysis

AIM:To investigate the efficacy of probiotics in irritable bowel syndrome(IBS) patients.METHODS:Pub Med,Cochrane library,Scopus,Google Scholar,and Clinicaltrial.gov databases were searched for literature published between September 2007 and December 2013.The applied Mesh terms were "probiotics," "irritable bowel syndrome," and "irritable bowel syndrome treatment." The collected data contained24 clinical trials,of which 15 were eligible for meta-analysis and nine were reviewed systematically.All studies were randomized placebo-controlled trials in patients with IBS that investigated the efficacy of probiotics in IBS improvement.The Jadad score was used to assess the methodological quality of trials.The quality scale ranges from 0 to 5 points,with a score ≤ 2 indicating a low quality report,and a score of ≥3 indicating a high quality report.Relative risk(RR),standardized effect size,and 95%CI were calculated using the Der Simonian-Laird method.The Cochran Q test was used to test heterogeneity with P < 0.05.Funnel plots were constructed and Egger's and BeggMazumdar tests were performed to assess publication bias.RESULTS:A total of 1793 patients were included in the meta-analysis.The RR of responders to therapies based on abdominal pain score in IBS patients for two included trials comparing probiotics to placebo was 1.96(95%CI:1.14-3.36;P = 0.01).RR of responders to therapies based on a global symptom score in IBS patients for two included trials comparing probiotics with placebo was 2.43(95%CI:1.13-5.21;P = 0.02).For adequate improvement of general symptoms in IBS patients,the RR of seven included trials(six studies) comparing probiotics with placebo was 2.14(95%CI:1.08-4.26;P = 0.03).Distension,bloating,and flatulence were evaluated using an IBS severity scoring system in three trials(two studies) to compare the effect of probiotic therapy in IBS patients with placebo,the standardized effect size of mean differences for probiotics therapy was-2.57(95%CI:-13.05--7.92).CONCLUSION:Probiotics reduce pain and symptom severity scores.The results demonstrate the beneficial effects of probiotics in IBS patients in comparison with placebo.

Effi cacy of tricyclic antidepressants in irritable bowel syndrome:A meta-analysis

We aimed to evaluate the efficacy of tricyclic antidepressants(TCAs) as a therapeutic option for irritable bowel syndrome(IBS) through meta-analysis of randomized controlled trials.For the years 1966 until September 2008,PubMed,Scopus,Web of Science,and Cochrane Central Register of Controlled Trials were searched for double-blind,placebo-controlled trials investigating the effi cacy of TCAs in the management of IBS.Seven randomized,placebo-controlled clinical trials met our criteria and were included in the metaanalysis.TCAs used in the treatment arm of these trials included amitriptyline,imipramine,desipramine,doxepin and trimipramine.The pooled relative risk for clinical improvement with TCA therapy was 1.93(95% CI:1.44 to 2.6,P<0.0001).Effect size of TCAs versus placebo for mean change in abdominal pain score among the two studies was -44.15(95% CI:-53.27 to -35.04,P<0.0001).It is concluded that low dose TCAs exhibit clinically and statistically signifi cant control of IBS symptoms.

Role of dietary polyphenols in the management of peptic ulcer

Peptic ulcer disease is a multifactorial and complex disease involving gastric and duodenal ulcers.Despite medical advances,the management of peptic ulcer and its complications remains a challenge,with high morbidity and death rates for the disease.An accumulating body of evidence suggests that,among a broad reach of natural molecules,dietary polyphenols with multiple biological mechanisms of action play a pivotal part in the management of gastric and duodenal ulcers.The current review confirmed that dietary polyphenols possess protective and therapeutic potential in peptic ulcer mediated by:improving cytoprotection,re-epithelialization,neovascularization,and angiogenesis; up-regulating tissue growth factors and prostaglandins; down-regulating anti-angiogenic factors; enhancing endothelial nitric oxide synthasederived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance,antacid,and antisecretory activity; increasing endogenous mucosal defensive agents; and blocking Helicobacter pylori colonization associated gastric morphological changes and gastroduodenal inflammation and ulceration.In addition,anti-inflammatory activity due to downregulation of proinflammatory cytokines and cellular and int e r c e llular adhe s ion age nt s,s uppr e s s ing leukocyte-endothelium interaction,inhibiting nuclear signaling pathways of inflammatory process,and modulating intracellular transduction and transcription pathways have key roles in the anti-ulcer action of dietary polyphenols.In conclusion,administration of a significant amount of dietary polyphenols in the human diet or as part of dietary supplementation along with conventional treatment can result in perfect security and treatment of peptic ulcer.Further welldesigned preclinical and clinical tests are recommended in order to recognize higher levels of evidence for the confirmation of bioefficacy and safety of dietary polyphenols in the management of peptic ulcer.

Herbal medicines for the management of irritable bowelsyndrome:A comprehensive review

Irritable bowel syndrome (IBS) is a functional gut disorder with high prevalence.Because of various factors involved in its pathophysiology and disappointing results from conventional IBS medications,the treatment of IBS is challenging and use of complementary and alternative medicines especially herbal therapies is increasing.In this paper,electronic databases including PubMed,Scopus,and Cochrane library were searched to obtain any in vitro,in vivo or human studies evaluating single or compound herbal preparations in the management of IBS.One in vitro,3 in vivo and 23 human studies were included and systematically reviewed.The majority of studies are about essential oil of Menta piperita as a single preparation and STW 5 as a compound preparation.Some evaluated herbs such as Curcuma xanthorriza and Fumaria officinalis did not demonstrate any benefits in IBS.However,it seems there are many other herbal preparations such as those proposed in traditional medicine of different countries that could be studied and investigated for their efficacy in management of IBS.

Systematic review of modulators of benzodiazepine receptors in irritable bowel syndrome:Is there hope?

Several drugs are used in the treatment of irritable bowel syndrome(IBS) but all have side effects and variable efficacy.Considering the role of the gut-brain axis,immune,neural,and endocrine pathways in the pathogenesis of IBS and possible beneficial effects of benzodiazepines(BZD) in this axis,the present systematic review focuses on the efficacy of BZD receptor modulators in human IBS.For the years 1966 to February 2011,all literature was searched for any articles on the use of BZD receptor modulators and IBS.After thorough evaluation and omission of duplicate data,10 out of 69 articles were included.BZD receptor modulators can be helpful,especially in the diarrhea-dominant form of IBS,by affecting the in? ammatory,neural,and psychologic pathways,however,controversies still exist.Recently,a new BZD receptor modulator,dextof isopam was synthesized and studied in human subjects,but the studies are limited to phase □b of BZDs in IBS,but bearing in mind the concentrationdependent effect of BZDs on cytokines and cell proliferation,future studies using pharmacodynamic and pharmacokinetic approaches are highly recommended.

Antioxidant therapy in the management of acute,chronic and post-ERCP pancreatitis:A systematic review

We systematically reviewed the clinical trials which recruited antioxidants in the therapy of pancreatitis and evaluated whether antioxidants improve the outcome of patients with pancreatitis.Electronic bibliographic databases were searched for any studies which investigated the use of antioxidants in the management of acute pancreatitis(AP)or chronic pancreatitis(CP)and in the prevention of post-endoscopic retrograde cholangio-pancreatography(post-ERCP)pancreatitis(PEP)up to February 2009.Twenty-two randomized,placebo-controlled,clinical trials met our criteria and were included in the review.Except for a cocktail of antioxidants which showed improvement in outcomes in three different clinical trials,the results of the administration of other antioxidants in both AP and CP clinical trials were incongruent and heterogeneous.Furthermore,antioxidant therapy including allopurinol and N-acetylcysteine failed to prevent the onset of PEP in almost all trials.In conclusion,the present data do not support a benefit of antioxidant therapy alone or in combination with conventional therapy in the management of AP,CP or PEP.Further double blind,randomized,placebo-controlled clinical trials with large sample size need to be conducted.

A systematic review of effi cacy and tolerability of mebeverine in irritable bowel syndrome

We evaluated the eff icacy and tolerability of mebeverine, a musculotropic antispasmodic agent, in irritable bowel syndrome (IBS) and compared its usual dosages by meta-analysis. Medical databases and all relevant literature were searched from 1965 to June 2009 for any placebo-controlled clinical trials of mebeverine, using search terms such as mebeverine, clinical trials, and IBS. Eight randomized trials met our criteria, including six trials that compared mebeverine with placebo and two that compared mebeverine tablets with capsules. These eight trials included 555 patients randomized to receive either mebeverine or placebo with 352 (63%)women and 203 (37%) men in all subtypes of IBS. The pooled relative risk (RR) for clinical improvement of mebeverine was 1.13 (95% CI: 0.59-2.16, P = 0.7056) and 1.33 (95% CI: 0.92-1.93, P = 0.129) for relief of abdominal pain. The efficacy of mebeverine 200 mg compared to mebeverine 135 mg indicated RRs of 1.12 (95% CI: 0.96-1.3, P = 0.168) for clinical or global improvement and 1.08 (95% CI: 0.87-1.34, P = 0.463) for relief of abdominal pain. Thus, mebeverine is mostly well tolerated with no signif icant adverse effects; however, its eff icacy in global improvement of IBS is not statistically signif icant.

Treatment of Helicobacter pylori infection: Current and future insights

Helicobacter pylori(H.pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide.H.pylori treatment still remains a challenge,since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance,mucosal drug concentration,patient compliance,side-effect profile and cost.While no new drug has been developed,current therapy still relies on different mixture of known antibiotics and anti-secretory agents.A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen.Bismuthcontaining quadruple treatment,sequential treatment or a non-bismuth quadruple treatment(concomitant) are also an alternative therapy.Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H.pylori after defeat of first-line therapy.The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies.Therefore,adding probiotic to the medications,developing anti-H.pylori photodynamic or phytomedicine therapy,and achieving a successful H.pylori vaccine may have the promising to present synergistic or additive consequence against H.pylori,because each of them exert different effects.

A review of the efficacy of traditional Iranian medicine forinflammatory bowel disease

The etiology of inflammatory bowel disease(IBD) is not yet known,but many factors such as defects in the immune system,oxidative stress,microbial content in the gastrointestinal tract,nuclear factor(NF)-κB,nitric oxide(NO),cyclooxygenase-2(Cox-2),and leukotriene B4(LB4) are thought to play a role in its pathogenesis.In traditional Iranian medicine(TIM),several medicinal plants are thought to be effective for the treatment of IBD.In this study,information on all of these remedies were derived from all available old sources such as documents or notes and books and were added to the information derived from modern medical databases covering all in vitro,in vivo and clinical trials.For some of these plants,only one or two mechanisms of action have been found such as in Cassia fistula,Lepidium sativum,and Bunium persicum.However,for some plants various mechanisms of action are known.For example,Commiphora mukul is effective in IBD due to its immunomodulatory,antioxidant,and antibacterial properties and it decreases NF-κB,NO and Cox-2.Another herb,Plantago ovata,has immunomodulatory,antioxidant,anti-inflammatory and wound healing activities and decreases NO and LB4.Considering the mechanisms of action of these plants,the combination of some of them may be useful because of their many mechanisms of action such as Pistacia lentiscus,Bunium persicum,Solanum nigrum,Plantago ovata,Boswellia,Solanum nigrum,Plantago ovata and Commiphora mukul.For some of the herbal products used in TIM such as oleogum resin from Commiphora myrrha,seeds of Ocimum basilicum,seeds of Linum usitatissimum,gum resin of Dracaena cinnabari,seeds of Plantago major,seeds of Lallementia royleana,and seeds of Allium porrum,there is no or not enough studies to confirm their benefits in IBD.It is suggested that an evaluation of the effects of these plants on different aspects of IBD should be performed.

Modification in Media Composition to Obtain Secretory Production of STxB-based Vaccines using Escherichia coli

Shiga toxin B-subunit (STxB) from Shigella dysenteriae targets in vivo antigen to cancer cells, dendritic cells (DC) and B cells, which preferentially express the globotriaosylceramide (Gb3) receptor. This pivotal role has encouraged scientists to investigate fusing STxB with other clinical antigens. Due to the challenges of obtaining a functional soluble form of the recombinant STxB, such as formation of inclusion bodies during protein expression, scientists tend to combine STxB with vaccine candidates rather than using their genetically fused forms. In this work, we fused HPV16 E7 as a vaccine candidate to the recombinantly-produced STxB. To minimize the formation of inclusion bodies, we investigated a number of conditions during the expression procedure. Then various strategies were used in order to obtain high yield of soluble recombinant protein from E. coli which included the use of different host strains, reduction of cultivation temperature, as well as using different concentrations of IPTG and different additives (Glycin, Triton X-100, ZnCl2). Our study demonstrated the importance of optimizing incubation parameters for recombinant protein expression in E. coli; also showed that the secretion production can be achieved over the course of a few hours when using additives such as glycine and Triton X-100. Interestingly, it was shown that when the culture mediums were supplemented by additives, there was an inverse ratio between time of induction (TOI) and the level of secreted protein at lower temperatures. This study determines the optimal conditions for high yield soluble E7-STxB expression and subsequently facilitates reaching a functionally soluble form of STxB-based vaccines, which can be considered as a potent vaccine candidate for cervical cancer.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.METHODS: Rats were divided into seven groups. Fourgroups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha(TNF-α) and interlukin-1β(IL-1β), myeloperoxidase(MPO), thiobarbituric acid reactive substances(TBARS), and ferric reduced ability of plasma(FRAP) were determined in the colon.RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α(114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β(24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS(0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO(15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP(23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.

Antidepressants can treat inflammatory bowel disease through regulation of the nuclear factor-κB/nitric oxide pathway and inhibition of cytokine production:A hypothesis

Inflammatory bowel disease (IBD) is a group of inflammatory disorders mainly affecting the colon and small intestine. The main types of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). UC is restricted to the large intestine whereas CD can affect any part of the gastrointestinal tract. Treating this disorder depends on the form and level of severity. Common treatment involves an anti-inflammatory drug, such as mesalazine, and an immunosuppressant, such as prednisone. Several signaling pathways, including nuclear factor (NF)-κB and nitric oxide (NO), and genetic and environmental factors are believed to play an important role in IBD. Amitriptyline is a commonly used antidepressant with known anti-inflammatory activities. Amitriptyline also acts on the NF-κB/NO pathway or cytokine production. Therefore, we hypothesize that antidepressants like amitriptyline can be pioneered and considered effective as an innovative and effective therapeutic in the treatment and attenuation of development of IBD in adjusted doses.

Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats

AIM: To study the combinative effects of nanocerium and selenium in a murine model of diabetes. METHODS: Cerium oxide (CeO2) nanoparticles (60 mg/kg per day) and sodium selenite (5 μmol/kg per day) aloneor in combination, or the metal form of CeO2 (60 mg/kg) were administered for 2 wk by intraperitoneal injection to streptozotocin-induced diabetic rats. At the end of treatment blood was collected, liver tissue dissected and then oxidative stress markers, extent of energy depletion and lipid prof ile were evaluated.RESULTS: Antioxidant enzymes and high density lipoprotein decreased whereas oxidative stress, adenosine diphosphate/adenosine triphospahte levels, cholesterol, triglyceride and low density lipoprotein increased on induction of diabetes. All were improved by a combination of nanocerium and sodium selenite. There was a relative amelioration by CeO2 nanoparticles or sodium selenite alone, but the metal form of CeO2 showed no signif icant improvement. CONCLUSION: The combination of nanocerium and sodium selenite is more effective than either alone in improving diabetes-induced oxidative stress.