The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines

Background:Despite the availability of chemotherapy drugs such as 5-fluorouracil(5-FU),the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects.This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines(AGS and EPG85-257).Materials and Methods:In this in vitro study,AGS and EPG85-257 cells were treated with different concentrations of celastrol,5-FU,and their combination.Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)assay.The synergistic effect of 5-FU and celastrol was studied using Compusyn software.The DNA content at different phases of the cell cycle and apoptosis rate was measured usingflow cytometry.Results:Co-treatment with low concentrations(10%inhibitory concentration(IC10))of celastrol and 5-FU significantly reduced IC50(p<0.05)so that 48 h after treatment,IC50 was calculated at 3.77 and 6.9μM for celastrol,20.7 and 11.6μM for 5-FU,and 5.03 and 4.57μM for their combination for AGS and EPG85-257 cells,respectively.The mean percentage of apoptosis for AGS cells treated with celastrol,5-FU,and their combination was obtained 23.9,41.2,and 61.9,and for EPG85-257 cells 5.65,46.9,and 55.7,respectively.In addition,the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase.Conclusions:Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells,additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol.

Insights into the anorexic mechanism of Khat:an integrated in vivo,ex vivo,and in silico investigations

Background:Chewing Khat(Catha edulis)releases cathine and cathinone,which may reduce appetite via an unknown mechanism.This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract(CEWE)on appetite biomarkers,gene expression,and body weight,using in vivo,ex vivo,and in silico models.Methods:Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments.Liquid chromatography-mass spectroscopy(LC-MS)-MS was used to detect cathinone and cathine in the murine blood.The effect of Khat on serotonin receptors was studied in isolated rat fundus samples.Docking of the two Khat ligands was performed on G(The 5-hydroxytryptamine-type 2C receptor(5-HT2C)in an agonist-bound active conformation)and H(5-HT2C in an antagonist-bound inactive conformation)proteins to determine which ligands are most likely to act as agonists or antagonists.Results:Significant differences(P<0.05)in body weight were observed between the CEWE-treated groups and the controls over eight weeks.However,the plasma leptin and ghrelin levels did not change significantly(P>0.05).The expression of the ghrelin and leptin genes was also unaffected,but the expression of the 5-hydroxytryptamine(5-HT)gene decreased(P<0.05)with CEWE treatment.CEWE antagonizes 5-HT receptors in isolated rat fundus samples.Docking findings indicated that the khat ligands bound to 5-HT2C receptors.Cathine and cathinone levels in rat plasma were measured.Conclusion:Khat extract may suppress appetite by antagonizing the 5-HT receptors.Further research is required to understand its mechanism and potential applications.

Molecular mechanism and functional consequences of lansoprazole-mediated heme oxygenase-1 induction

AIM： To investigate the molecular mechanism and functional consequences of heme oxygenase-1 （HO-1） activation by lansoprazole in endothelial cells and macrophages. METHODS： Expression of HO-1 mRNA was analyzed by Northern blotting. Western blotting was used to determine the HO-1 and ferritin protein levels. NADPH-dependent reactive oxygen species （ROS） formation was measured with lucigenin-enhanced chemiluminescence. HO-1 promoter activity in mouse fibroblasts, stably transfected with a 15-kb HO-1 gene that drives expression of the reporter gene luciferase, was assessed usingin vivo bioluminescence imaging. RESULTS： Lansoprazole levels in endothelial cells increased HO-1 mRNA and HO-1 protein levels in macrophages. In addition, lansoprazole-induced ferritin protein levels in both cell systems. Moreover, induction of the antioxidant proteins HO-1 and ferritin by lansoprazole was followed by a decrease in NADPH- mediated ROS formation. The radical scavenging properties of lansoprazole were diminished in the presence of the HO inhibitor, chromium mesoporphyrin IX. Induction of HO-1 gene expression by lansoprazole was not related to oxidative stress or to the activation of the mitogen-activated protein kinase pathway. However, the phosphatidylinositol 3-kinase inhibitor LY294002 showed a concentration-dependent inhibition of HO-1 mRNA and promoter activity.CONCLUSION： Activation of HO-1 and ferritin may account for the gastric protection of lansoprazole and is dependent on a pathway blocked by LY294002.

Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: Effectiveness and mechanism of action

The effect of tea tree oil(TTO),cumin oil(CO),rose oil(RO)and aloe vera oil(AVO)on the skin permeation of losartan potassium(LP)was investigated.In vitro skin permeation studies were carried out using rat skin.The mechanism of skin permeation enhancement of LP by essential oils treatment was evaluated by FTIR,DSC,activation energy measurement and histopathological examination.Both concurrent ethanol/enhancer treatment and neat enhancer pretreatment of rat SC with all the oils produced significance increase in the LP flux over the control.The effectiveness of the oils as the penetration enhancers was found to be in the following descending order:AVO>RO>CO>TTO.However,only AVO was the only enhancer to provide target flux required to deliver the therapeutic transdermal dose of LP.FTIR and DSC spectra of the enhancer treated SC indicated that TTO,CO,RO and AVO increased the LP permeation by extraction of SC lipids.The results of thermodynamic studies and histopathological examination of AVO treated SC suggested additional mechanisms for AVO facilitated permeation i.e.transient reduction in barrier resistance of SC and intracellular transport by dekeratinization of corneocytes which may be attributed to the presence of triglycerides as constituents of AVO.It is feasible to deliver therapeutically effective dose of LP via transdermal route using AVO as penetration enhancer.

A classification system for tableting behaviors of binary powder mixtures

The ability to predict tableting properties of a powder mixture from individual components is of both fundamental and practical importance to the efficient formulation development of tablet products. A common tableting classification system(TCS) of binary powder mixtures facilitates the systematic development of new knowledge in this direction. Based on the dependence of tablet tensile strength on weight fraction in a binary mixture,three main types of tableting behavior are identified. Each type is further divided to arrive at a total of 15 sub-classes. The proposed classification system lays a framework for a better understanding of powder interactions during compaction. Potential applications and limitations of this classification system are discussed.

Carbamazepine solubility enhancement in tandem with swellable polymer osmotic pump tablet: A promising approach for extended delivery of poorly water-soluble drugs

Elementary osmotic pump(EOP)is a unique extended release(ER)drug delivery system based on the principle of osmosis.It has the ability to minimize the amount of the drug,accumulation and fluctuation in drug level during chronic uses.Carbamazepine(CBZ),a poorly water-soluble antiepileptic drug,has serious side effects on overdoses and chronic uses.The aim of the present study was to design a new EOP tablet of CBZ containing a solubility enhancers and swellable polymer to reduce its side effects and enhance the patient compliance.Firstly,a combination of solubilizing carriers was selected to improve the dissolution of the slightly soluble drug.Then,designing the new EOP tablet and investigating the effect of different variables of core and coat formulations on drug release behavior by single parameter optimization and by Taguchi orthogonal design with analysis of variance(ANOVA),respectively.The results showed that CBZ solubility was successfully enhanced by a minimum amount of combined polyvinyl pyrrolidone(PVP K30)and sodium lauryl sulfate(SLS).The plasticizer amount and molecular weight(MW)together with the osmotic agent amount directly affect the release rate whereas the swellable polymer amount and viscosity together with the semi-permeable membrane(SPM)thickness inversely influence the release rate.In addition,the tendency of following zero order kinetics was mainly affected by the coat components rather than those of the core.Further,orifice size does not have any significant effect on the release behavior within the range of 0.1 mm to 0.8 mm.In this study we report the successful formulation of CBZ-EOP tablets,which were similar to the marketed product Tegretol CR 200 and able to satisfy the USP criterion limits and to deliver about 80%of CBZ at a rate of approximately zero order for up to 12 h.

Quantitative prediction of the bitterness of atomoxetine hydrochloride and taste-masked using hydroxypropyl-β-cyclodextrin:A biosensor evaluation and interaction study

The bitterness of a drug is a major challenge for patient acceptability and compliance,especially for children.Due to the toxicity of medication,a human taste panel test has certain limitations.Atomoxetine hydrochloride(HCl),which is used for the treatment of attention deficit/hyperactivity disorder(ADHD),has an extremely bitter taste.The aim of this work is to quantitatively predict the bitterness of atomoxetine HCl by a biosensor system.Based on the mechanism of detection of the electronic tongue(Etongue),the bitterness of atomoxetine HCl was evaluated,and it was found that its bitterness was similar to that of quinine HCl.The bitterness threshold of atomoxetine HCl was 8.61μg/ml based on the Change of membrane Potential caused by Adsorption(CPA)value of the BT0 sensor.In this study,the taste-masking efficiency of 2-hydroxypropyl-β-cyclodextrin(HP-β-CyD)was assessed by Euclidean distances on a principle component analysis(PCA)map with the SA402B Taste Sensing System,and the host–guest interactions were investigated by differential scanning calorimetry(DSC),powder X-ray diffraction(XRD),nuclear magnetic resonance(NMR)spectroscopy and scanning electron microscopy(SEM).Biosensor evaluation and characterization of the inclusion complex indicated that atomoxetine HCl could actively react with 2-hydroxypropyl-β-cyclodextrin.

Succinylated whey protein isolate as a sustained-release excipient of puerarin derivative oral tablets:Preparation,optimization and pharmacokinetics

This work was done to investigate succinylated commercial whey protein isolate(S-WPI)as an oral sustained-release delivery carrier for puerarin 5(PR-5). The succinylation condi-tions were established for S-WPIs by optimization of single factor study and Box–Beehnkendesign. The effect of succinylation degree on S-WPIs solubility was evaluated. Physicochem-ical properties of S-WPIs dried by different three methods on their flow ability, particle size,morphology and in vitro release behavior were studied. After preparing PR-5 sustained re-lease protein tablets with S-WPIs as the carrier by direct powder compression method, thedrug release were studied in vitro and the oral pharmacokinetics and bioavailability wasevaluated using in vivo dog model. It was observed that concentration of substrate has asignificant effect on succinylation. Release behavior in vitro showed spry dried S-WPIs with100% succinylation rate and 30% drug loading would be applied to the preparation of PR-5 sustained-release protein tablets based on the swelling mechanism(protein loss). Comparedwith PR-5 conventional tablet with oral administration, T max value of PR-5 sustained-releaseprotein tablets was approximately 1.58 fold greater than those of the conventional tablets asfurther evidenced by the significantly prolonged MRT and T 1/2. The findings demonstratedthat spray-dried S-WPIs has potential as a promising functional excipient for the design of PR-5 oral sustained-release tablets which can fully improve sustained-release effect and oral bioavailability.

Sinapic acid ameliorates D-galactosamine/lipopolysaccharideinduced fulminant hepatitis in rats:Role of nuclear factor erythroidrelated factor 2/heme oxygenase-1 pathways

BACKGROUND Sinapic acid(SA)has been shown to have various pharmacological properties such as antioxidant,antifibrotic,anti-inflammatory,and anticancer activities.Its mechanism of action is dependent upon its ability to curb free radical production and protect against oxidative stress-induced tissue injuries.AIM To study the hepatoprotective effects of SA against lipopolysaccharide(LPS)/Dgalactosamine(D-GalN)-induced acute liver failure(ALF)in rats.METHODS Experimental ALF was induced with an intraperitoneal(i.p.)administration of 8μg LPS and 800 mg/kg D-GalN in normal saline.SA was administered orally once daily starting 7 d before LPS/D-GalN treatment.RESULTS Data showed that SA ameliorates acute liver dysfunction,decreases serum levels of alanine transaminase(ALT),and aspartate aminotransferase(AST),as well as malondialdehyde(MDA)and NO levels in ALF model rats.However,pretreatment with SA(20 mg/kg and 40 mg/kg)reduced nuclear factor kappalight-chain-enhancer of activated B cells(NF-κB)activation and levels of inflammatory cytokines(tumor necrosis factor-αand interleukin 6).Also,SA increased the activity of the nuclear factor erythroid-related factor 2/heme oxygenase-1(Nrf2/HO-1)signaling pathway.CONCLUSION In conclusion,SA offers significant protection against LPS/D-GalN-induced ALF in rats by upregulating Nrf2/HO-1 and downregulating NF-κB.

Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells

Non-small cell lung cancer(NSCLC)is often characterized by an underlying mutation in the epidermal growth factor receptor(EGFR),contributing to aggressive metastatic disease.Methyl 2-cyano-3,11-dioxo-18 beta-olean-1,12-dien-30-oate(CDODA-Me),a glycyrrhetinic acid derivative,reportedly improves the therapeutic response to erlotinib(ERL),an EGFR tyrosine kinase inhibitor.In the present study,we performed a series of studies to demonstrate the efficacy of CDODA-Me(2μM)in sensitizing HCC827 R(ERL-resistant)cells to ERL.Herein,we first established the selectivity of ERL-induced drug resistance in the HCC827 R cells,which was sensitized when ERL was combined with CDODA-Me(2μM),shifting the IC50 from 23.48μM to 5.46μM.Subsequently,whole transcriptomic microarray expression data demonstrated that the combination of ERL+CDODA-Me elicited 210 downregulated genes(0.44%of the whole transcriptome(WT))and 174 upregulated genes(0.36%of the WT),of which approximately 80%were unique to the ERL+CDODA-Me group.Synergistic effects centered on losses to cell cycle progression transcripts,a reduction of minichromosome maintenance complex components(MCM2-7),all key components of the Cdc45·MCM2-7 GINS(CMG)complex,and replicative helicases;these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress,including sulfiredoxin 1,heme oxygenase 1,and stress-induced growth inhibitor 1.Collectively,these findings indicate that the synergistic therapeutic effects of ERL+CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.

Quantitative estimation of hesperidin by HPTLC in different varieties of citrus peels

Objective:To develop a simple,selective,sensitive and accurate high-performance thin layer chromatography(HPTLC)method to determine the quantity of hesperidin in different varieties of citrus fruits.Methods:The method was carried out in aluminum-backed silica gel 60 F_(254)plates with ethyl acetate-methanol-water 15:3:2(%,v/v)as mobile phase.Results:A compact band was obtained for hesperidin at R_f value of(0.40±0.04).The calibration plot was linear in the range of 100-800 ng/spot of hesperidin and the correlation coefficient of 0.9986was indicative of good linear dependence of peak area on concentration.Limit of detection(8.87ng/spot),limit of quantification(23.21 ng/spot),accuracy(less than 2%)and recovery(ranging from98.55-99.38)were found satisfactory.Conclusions:The method developed can be used for routine analysis of hesperidin in crude drug as well as in herbal and pharmaceutical dosage form containing citrus fruits as an ingredient.

Anti-diabetics and antimicrobials:Harmony of mutual interplay

Diabetes is one of the four major non-communicable diseases,and appointed by the world health organization as the seventh leading cause of death worldwide.The scientists have turned over every rock in the corners of medical sciences in order to come up with better understanding and hence more effective treatments of diabetes.The continuous research on the subject has elucidated the role of immune disorders and inflammation as definitive factors in the trajectory of diabetes,assuring that blood glucose adjustments would result in a relief in the systemic stress leading to minimizing inflammation.On a parallel basis,microbial infections usually take advantage of immunity disorders and propagate creating a pro-inflammatory environment,all of which can be reversed by antimicrobial treatment.Standing at the crossroads between diabetes,immunity and infection,we aim in this review at projecting the interplay between immunity and diabetes,shedding the light on the overlapping playgrounds for the activity of some antimicrobial and anti-diabetic agents.Furthermore,we focused on the antidiabetic drugs that can confer antimicrobial or anti-virulence activities.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer

BACKGROUND Connective tissue growth factor(CTGF)is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling,inflammatory processes and fibrosis in various illnesses including cancer.AIM To investigate the role of CTGF in colorectal cancer(CRC)progression and to compare the CTGF expression with different clinicopathological parameters.METHODS Real-time polymerase chain reaction,immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16.RESULTS CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens.The higher protein expression levels showed a significant association with smoking,staging,tumor grade,invasion depth,necrosis of tumor tissue,and both lymphovascular and perineural invasion.As per the cox regression model and classification tree analysis,tumor-nodemetastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients.Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival.CONCLUSION Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients.These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

Measurement and correlation of solubility of diosmin in four pure solvents and β-cyclodextrin solution at 298.15K to 333.15K

The aim of present study was to measure and correlate the solubility of poorly water-soluble flavonoid diosmin in water, ethanol, isopropyl alcohol （IPA）, polyethylene glycol-400 （PEG-400） and β-cyclodextrin （β-CD） aqueous solution （0.02 mol·L^-1 ）. The solubility of diosmio was measured using the shake flask method from （298.15 to 333.15） K at atmospheric pressure. The experimental solubilities of diosmin were regressed by the modified Apelblat model with a relative deviation in the range of 0.048% to 5.940%. The correlation coefficients were observed in the range of 0.9957 to 0.9995. The solubility of diosmin was found to be increased with temperature in all sample matrices investigated. The mole fraction solubility of diosmin was found to be higher in 5-CD aqueous solution and PEG-400 as compared to water, ethanol and IPA. Based on solubility data of present study, diosmin was considered as practically insoluble in water, insoluble in ethanol ＆ IPA and soluble in PEG- 400 and β-CD aqueous solution.

Development,characterization and solubility enhancement of comparative dissolution study of second generation of solid dispersions and microspheres for poorly water soluble drug

The poor dissolution characteristics of water-insoluble drugs are a major challenge for pharmaceutical scientists.Reduction of the particle size/increase in the surface area of the drug is a widely used and relatively simple method for increasing dissolution rates.The objective of this study was to improve solubility,release and comparability of dissolution of a poorly soluble drug using two different types of formulations(solid dispersions and microspheres).Hydrochlorothiazide was used as a model drug.The solid dispersions and microspheres were prepared by solvent evaporation method using ethyl cellulose,hydroxypropyl methylcellulose in different drug-to-carrier ratios(1:1,1:2 w:w).The prepared formulations were evaluated for interaction study by Fourier transform infrared spectroscopy,differential scanning calorimetry,percentage of practical yield,drug loading,surface morphology by scanning electron microscopy,optical microscopy and in-vitro release studies.The results showed no interaction between the drug and polymer,amorphous state of solid dispersions and microspheres,percentage yield of 42.53%to 78.10%,drug content of 99.60%to 99.64%,good spherical appearance in formulation VI and significant increase in the dissolution rate.

Preparation of highly stable diclofenac potassium pellet with microcrystalline cellulose by extrusionespheronization

The main purpose of this study is to prepare highly stable diclofenac potassium(DP)pellet with microcrystalline cellulose(MCC)by extrusionespheronization.Using MCC,DP pellets were prepared and the stability was investigated.Related compounds of DP pellets were analyzed by High Pressure Liquid Chromatography(HPLC).After stability test of 60℃/75%RH for 10 d,the values of two main related compounds were 0.94%and 2.17%,respectively.Compatibility tests show that instability of DP was mainly caused by MCC.To improve the stability of DP in presence of MCC,different kinds of stabilizers were investigated.Upon addition of 1.5%(w/w)sodium hydroxide,the primary related compound of pellets was reduced to be 0.159%after stability test of 60℃/75%RH for 50 d.This study demonstrated that MCC induced decomposition of DP upon exposure to moisture could be prohibited by addition of sodium hydroxide.The mechanisms were discussed and residual hydroxyl free radicals in excipients were responsible for decomposition of DP.Finally,this formulation of DP is highly stable with sustained-release behavior.

Incompatibility of Paracetamol with Pediatric Suspensions Containing Amoxicillin, Azithromycin and Cefuroxime Axetil

The main objective of this work was to use the Differential Scanning Calorimetry (DSC) and FTIR spectroscopy to study the possible drug-drug or drug-excipient (s) interaction in case of concomitant oral administration of paracetamol with the most common used antibiotics for children. Amoxicillin, azithromycin, cefuroxime axetil and their commercially available suspensions, Amoxil?, Azithromax? and Zinnat? were used. DSC curves for paracetamol, pure antibiotics, commercially available antibiotics and all binary mixtures used in this study showed drug-drug or drug-excipient (s) physical interaction and indicated a possible chemical interaction. To confirm chemical drug-drug or drug-excipient (s) interaction additional ATR-IR spectra for all samples used in this study were obtained. Results obtained from ATR-IR spectra showed drug-excipient (s) interaction in Zinnat?, Azithromax? and binary mixture Azithromax?-paracetamol, while chemical drug-drug interaction was not observed. From this study it can be concluded that the concomitant oral administration of paracetamol with commercially available antibiotics used in this study is not recommended and duration of two hours between the oral administrations of these drugs is strongly recommended to avoid drug-drug or drug-excipient (s) interaction.

Antimicrobial Activities of Seed Extracts of Mango (<i>Mangifera indica</i>L.)

Mangifera indica L. is a species of mango in the Anacardiaceae family. It is found in the wild in tropical regions and cultivated varieties have been introduced to other warm regions of the world. This present study aimed to investigate the in vitro antimicrobial activities of methanol and ethanol extracts of mango seed against 25 representatives gram positive, gram negative, acid fast bacteria and fungi. Mango fruit seed were extracted by Soxhlet using methanol and ethanol as solvents. The extracts were tested against the microorganisms using disc diffusion method at different concentrations: 5 mg/mL, 3.75 mg/mL, 3.125 mg/mL, 2.5 mg/mL, 1.875 mg/mL and 1.25 mg/mL). In vitro antibacterial activities of methanol and ethanol extracts of mango bulb showed inhibitions to tested organisms with variable inhibition zones. Except one organism (Rhodococcus equi), no resistance among the tested strains was shown. The mean zone of inhibition produced ranged between 5 mmand18 mmwith18 mm/Mycobacterium smegmatis showed the highest zone of inhibition. In most test strains comparable zones of inhibitions were noted for both methanol and ethanol extract. Candida albicans and Aspergilllus niger were both inhibited by the extracts. The methanol and ethanol extracts of mango seed showed good inhibitory effects against almost all tested strains. The inhibition zones produced by mango extract were less than those produced by standard positive control drug. This could be due to low diffusion rate of mango extract in agarose medium, a thing needed to be further investigated. The products are potential new antimicrobial therapy in the ethnopharmacology domain.

Design and <i>in Vitro</i>Evaluation of Eudragit^®S100/Lipid Based Simvastatin Chronotherapeutic Drug Delivery System

The present study was undertaken to 1) formulate a pulsatile colonic delivery of simvastatin (SIM) as chronotherapy for treatment of hypercholesterolemia, and 2) enhance the dissolution profile of the prepared SIM chronotherapeutic system. Lipid based formulations were utilized to formulate SIM in capsule dosage form coated with Eudragit&reg S100. SIM was formulated using different percentages of Cremophor EL40, Capmul MCM EP and PEG 400. SIM coated capsules (SIMcc) were evaluated for drug release in different pH media. The results showed that SIMcc were able to withstand the acidic pH for 2 hours. Drug release rate was higher (88%) from SIMcc containing 10% polyethylene glycol (PEG) 400. In conclusion, Eudragit&reg S100 as time-dependent and site specific polymer retards SIM release from coated capsules;hence SIMcc could be considered as successful pulsatile treatment of hypercholesterolemia. Also, dissolution profile of lipid based SIMcc was enhanced in comparison with that of SIM filled capsules.

Proteome-wide screening for the analysis of protein targeting of Chlamydia pneumoniae in endoplasmic reticulum of host cells and their possible implication in lung cancer development

Available reports have confirmed a link between bacterial infection and the progression of different types of cancers,including colon,lungs,and prostate cancer.Here we report the Chlamydia pneumonia proteins targeting in endoplasmic reticulum(ER)using in-silico approaches and their possible role in lung cancer etiology.We predicted 48 proteins that target human ER,which may be associated with protein folding and protein-protein interactions during infection.The results showed C.pneumoniae proteins targeting human ER and their implications in lung cancer growth.These targeted proteins may be involved in competitive interactions between host and bacterial proteins,which may change the usual pathway functions and trigger the development of lung cancer.Moreover,C.pneumoniae unfolded protein accumulation in the human ER possibly induces ER stress,consequently activating the unfolded protein response(UPR),and providing a favorable microenvironment for cancer growth.The current study showed the C.pneumoniae protein targeting in ER of host cell and their implication in lung cancer growth.These results may help researchers better manage lung cancer and establish a molecular mechanism for C.pneumoniae lung cancer association.