Effect of whole methanolic extract of Galium verum on AGO cell line

Objectives:Although many studies have suggested the anticancer properties of Galium verum,there is still no accurate information regarding its side effects on normal cells.Accordingly,this study aimed to investigate the dual effects of the whole Galium verummethanolic extract on the normal human fibroblast cell line(AGO)cell line at different concentrations.Methods:The cell line was randomly divided into a control group and groups exposed to concentrations of 12.5 to 400μg/mL.Extraction was performed by the maceration method.In addition,the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)method was applied to measure cytotoxicity and flow cytometry.Further,BCL2 associated X(BAX)andB-cell lymphoma 2(BCL2)genes were expressed by the real-time polymerase chain reaction to evaluate apoptosis and reactive oxygen species(ROS).Finally,data were compared between groups using a one-way analysis of variance.Results:A significant reduction was observed in the cell viability of 90%at a concentration of 400μg/mL compared to the control.In comparison,a significant increase was reported in cell viability at concentrations of 25-200μg/mL(P<0.0001).Furthermore,there was a significant 2.87-time increase in apoptosis compared to the control group(P<0.0001),but no significant differences were reported in cellular phases.ROS increased significantly by 5.7 times(P<0.05),and a significant 80-fold increase was found in the BAX/BCL2gene ratio(P<0.05).Conclusion:The whole methanolic extract could lower the viability of human fibroblasts at 400μg/mL and more by increasing apoptosis,thereby increasing BAX/BCL2gene expression and ROS production.However,the extract exerted an increased effect on cell viability in a concentration-dependent manner on AGO and increased cell growth at concentrations less than 400μg/mL,highlighting different effects of the whole extract on the AGO cell line.

Molecular docking of amphetamine,cathine and cathinone with dihydrofolate reductase:a computational analysis of inhibition of dihydrofolate reductase by khat alkaloids

Interaction of amphetamine,cathine and cathinone with the enzyme dihydrofolate reductase was studied by molecular docking using AutoDock 4.2 as the docking software application.AutoDock 4.2 software serves as a valid and acceptable docking application to study the interactions of small compounds with proteins.Interactions of amphetamine,cathine and cathinone with dihydrofolate reductase were compared to those of methotrexate,a known inhibitor of the enzyme.The calculated free energy of binding(ΔG binding)shows that the three ligands(ΔG=-6.87 to-7.21 kcal/mol;Ki=9.15 to 5.18μM)bind with affinity slightly lower than methotrexate(ΔG=-8.78 kcal/mol;Ki=363 nM).Binding interactions of the three ligands with active site residues of the enzyme are also predicted.All the ligands appear to bind in a similar conformation making extensive VDW contacts in the active site of the enzyme.Hydrogen bonding and pi-pi interaction with key active site residues is also observed.Thus,a probable inhibition of dihydrofolate reductase by khat alkaloids can be explained on the basis of this in silico binding and khat alkaloids can be considered as potential lead compounds in the development of new inhibitors of dihydrofolate reductase which is a potential target of anti-cancer drugs.The results of these studies can serve as a starting point for further computational and experimental studies.

Evaluation of cytotoxicity of rubiadine on MCf7 and AGO cell lines

Background:Rubiadineis a bioactive substance with anthraquinone structure and rubiadine family that is isolated from Nonior Morinda citrifolia(Indian berry).The root of this plant can be used to treat inflammation and congestion of the kidneys and various cancers.Due to the fact that studies on the anti-cancer effects of rubiadine on breast cancer cells are very limited,this study aimed to investigate the effects of rubiadine-induced cytotoxicity on breast cancer and normal cells.Methods:In this experimental-laboratory study,breast cancer cell line(MCf7)and normal human fibroblast cell line(AGO)were purchased from Pasteur Institute,Iran,and given to the control groups(no exposure to rubiadine)and the groups exposed to rubiadine with concentrations of 12.5,6.25,12.5,3.5,1.56,0.78,and 0.39μg/mL.Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.The expression of BCL2 associated X(BAX)andB-cell lymphoma 2(BCL2)genes was also evaluated using real-time Polymerase chain reaction.Data were analyzed using a one-way analysis of variance.Results:The results of this study showed that concentrations of 12.5,6.25,1.56 and 0.39μg/mL reduced breast cancer viability(P<0.001).The concentration of inhibitory concentration(IC50)μg/mL was reported to be 1.89.Gene expression BAX and BAX/BCL2 was significantly increased in breast cancer cells with IC501.89μg/mL rubiadine compared to the control group(P<0.01 and P<0.05).Also,Gene expression BCL2 did not decrease significantly.A significant increase in BAX/BCL2 expression was observed compared to the control group(P<0.05).Conclusions:Changes in gene expression did not affect normal cells.Different concentrations of rubiadine cause cytotoxic effects by increasing BAX/BCL2 expression on breast cancer cells and did not affect normal cells.

Prediction of the mechanisms of liver injury of Epimedii Folium by network pharmacology and validation in HepaRG Cells

Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.

The mechanism of hepatotoxicity of Nux Vomica:a network-pharmacology-based study

Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.

Overview about toxicology of cannabis smoking

There are other names for cannabis in the market such as marijuana and hashish.Inhalation considers to be the most common way for consumption.As the inhaled cigarette which called in some communities(joint)contains 0.5 to 0.7 g of delta-9-THC,but the most common dose contains 5-25 mg THC.It can be smoked directly or through small pipes[6].It was demonstrated that the physiologic effects result from oral consumption are slower in onset and have longer duration compared to that with inhalation administration.As a consequence,the patients may lead to ingest more cannabis and be affected more strongly and for longer than intended.There are other products considered to increase the risk of toxicity such as tinctures,capsules and topical.These preparations are limited in use.Furthermore,the additional chemicals and adulterants participate in a particular way to increase the risk of toxicity.As most of cannabis users are unaware by the presence of these chemicals.The only way of identification is when the user subjected to toxicological evaluation as part of a forensic investigation,for example,if being arrested for driving while under the influence of cannabis[3].

Regulatory framework of cosmetic in the European Union

Cosmetics that are personal or personalized are now becoming extremely prevalent.While compliance is mandated by European Union(EU)Cosmetics Directive 1223/2009,there seem to be no strict guidelines for maintaining obedience.Cosmetics must meet a number of conditions in order to be sold in the European Single Market;however,the focus of this article is on the Cosmetics Regulation 1223/2009.Regulations are examined for certain elements and several solutions are presented that allow for careful use of individually cloaked cosmetics that are available on the market.Metallic nanoparticles(NMs)have been proposed for usage as active ingredients/excipient in a number of cosmetics products.Due to fast-paced businesses in the cosmetic industry,cosmetology tends to focus on its distinctive characteristics to bring value to a diverse array of products,but due to the small size of nanometers,NMs may not always follow the very same handling guidelines as their conventional material.As a result,a nano-specific framework for regulating the use of nanomaterials&creation of nano-improved cosmetics is becoming increasingly prevalent.Scientific and industrial perspective into the NMs presently used for the m arketplace,with an emphasis on metallic NMs,and also an evaluation of the regulatory requirements and Scientific Commission on Consumer Safety(SCCS)Opinions.Considering the fact that the original Cosmetic products Directive(EU Legislation No 1223/2009)has precise restrictions on NMs,beauty materials containing unlawful NMs have already been supplied in the EU on numerous times.Researchers examine the risk evaluation indicated in Article 16 of the Cosmetology Code acts as a framework for the potential expansion to enhance nano-items,considering the long-term risks of nanomaterials if mistreated.The nation’s attention is on synchronizing efforts to integrate metallic NMs into cosmetic products but to the restricted fusion of metallic NMs with numerous non-metallic n anoparticles.Although Directive 76/768/EEC on the beauty items is an upright division of amendment that requires the European market for every cosmetic product placed to meet its exigencies would be irrational that it is for believings a stand-alone part of regulations is unaffected by other legal texts.In reality,D irective 76/768/EEC takes the form part of complicated legal action that began 40 years ago that ensure the free passage of goods throughout the EU while also European individuals’and their environment’s safety.The ongoing chapter outlines the most important aspects of the Directive Cosmetic Products along with the latest guidelines 2022 prepared by the COS law Team of what happened in the EU cosmetics regulatory framework between January and March,which serves as the book’s foundation.The trend of personal skincare seems to be high among clients.

Exposure to sharp injuries among hospital medical waste handlers

Dear editor Health care workers are generally predisposed to injuries from sharps as a health hazard.This is more pronounced among waste handlers.Exposure to medical waste in hospitals and health facilities results in injuries and contagious diseases.Therefore,health workers,including nurses,doctors,technicians,and hospital cleaning workers,are always alerted to exercise the utmost caution and not to be exposed to the waste produced by the patient,especially through cuts or scrapes from the patient’s sharp injuries,touching or inhalation or exposure to spills or splashes of liquids from medical waste or any waste resulting from patient care or contact with his body fluids[1].

Angel or d evil?M edicinal history of poppy in traditional C hinese medicine

Poppy,the main raw material for making and extracting of opium,its extract is also a source of various sedatives,such as morphine,thebaine,codeine,papaverine,and noscapine.The Papaveraceae Papaver genus plant was once used as a medicine in the history of traditional Chinese medicine.