<i>In Vitro</i>Studies of NIPAAM-MAA-VP Copolymer-Coated Magnetic Nanoparticles for Controlled Anticancer Drug Release

Thermosensetive poly(N-isopropylacrylamide)-based magnetic nanoparticles were synthesized by free radical polymerization of N-isopropylacrylamide (NIPPAMs), methacrylic acid (MAA), and vinyl pyrrolidone (VP) in the presence of methylene-bis-acrylamide as cross linking agent. The Fe3O4 magnetic nanoparticls were prepared by chemical precipitation of Fe salts in the ratio of 1:2 under alkaline and inert condition. Thermosensitive crosslinked P (NI-PAAM-MAA-VP) copolymers were characterized by FT-IR and H-NMR. The pH and thermosensitive copolymer was used for preparation of drug loaded magnetic nanoparticles, and doxorubicin (DOX) was used as a typical anticancer drug. The amount of the loaded drug and drug release amount were determined by UV measurements. Scanning electron microscopy (SEM) and lower critical solution temperature (LCST) were used to determine the particle surface morphology and the phase transition temperature of the nanoparticles respectively. The release behavior of DOX at pH = 7.4 and 37°C was studied. The result indicated that this thermosensetive magnetic nanoparticle has a high drug loading capacity and favorable linear release property for DOX without initial burst release. Thus this system is promising for the application in targeted smart anticancer drug delivery.

Combination therapy using evening primrose oil and electrical stimulation to improve nerve function following a crush injury of sciatic nerve in male rats

Peripheral nerve injuries with a poor prognosis are common.Evening primrose oil（EPO） has beneficial biological effects and immunomodulatory properties.Since electrical activity plays a major role in neural regeneration,the present study investigated the effects of electrical stimulation（ES）,combined with evening primrose oil（EPO）,on sciatic nerve function after a crush injury in rats.In anesthetized rats,the sciatic nerve was crushed using small haemostatic forceps followed by ES and/or EPO treatment for 4 weeks.Functional recovery of the sciatic nerve was assessed using the sciatic functional index.Histopathological changes of gastrocnemius muscle atrophy were investigated by light microscopy.Electrophysiological changes were assessed by the nerve conduction velocity of sciatic nerves.Immunohistochemistry was used to determine the remyelination of the sciatic nerve following the interventions.EPO ＋ ES,EPO,and ES obviously improved sciatic nerve function assessed by the sciatic functional index and nerve conduction velocity of the sciatic nerve at 28 days after operation.Expression of the peripheral nerve remyelination marker,protein zero（P0）,was increased in the treatment groups at 28 days after operation.Muscle atrophy severity was decreased significantly while the nerve conduction velocity was increased significantly in rats with sciatic nerve injury in the injury ＋ EPO ＋ ES group than in the EPO or ES group.Totally speaking,the combined use of EPO and ES may produce an improving effect on the function of sciatic nerves injured by a crush.The increased expression of P0 may have contributed to improving the functional effects of combination therapy with EPO and ES as well as the electrophysiological and histopathological features of the injured peripheral nerve.

Effect of pyrite content of feed and configuration of locked particles on rougher flotation of copper in low and high pyritic ore types

Misreported pyrite into copper concentrates dramatically declines copper grade and recovery. Copper flotation can be also more complicated if flotation feed comes from an elevated-pyritic copper ore. In this investigation, the effect of two different ore types(high pyritic and low pyritic feeds) was studied on rougher stage of industrial copper flotation circuit. Samples were taken from different streams and the structure of chalcopyrite within the pyrite and non-sulfide gangue minerals was examined in various size fractions for mentioned ore types. Results indicated that 72% and 56% of the total floated pyrite was transferred to concentrate in first four cells in the low and high pyritic feeds, respectively. Whereas, this proportion for floated SiO_2 in last ten cells was detected as 72% and 71%, respectively. A detailed interpretation of the effect of locked particles in different size fractions on rougher flotation cells is studied from industrial point of view.

Diagnosis of Toxoplasma gondii infection in pregnant women using automated chemiluminescence and quantitative real time PCR

Objective: To identify serodiagnosis and quantification of Toxoplasma gondii(T. gondii) infection among pregnant women in Salmas, northwest of Iran. Methods: In this crosssectional study, 276 blood samples were collected from pregnant women referred to the health care centers in Salmas city. The demographic variables were also recorded. Titers of antiToxoplasma IgM and IgG antibodies(Ab) were determined using the chemiluminescence immunoassay. Quantitative real-time PCR targeting the T. gondii repeated element gene was also performed on the blood sample. Results: Out of all, 19.92%(55/276) and 2.17%(6/276) patients were seropositive for anti-Toxoplasma IgG and IgM Ab, respectively. Moreover, the presence of T. gondii DNA was observed in 12.31%(34/276) blood samples. A significant relationship was observed between the IgG Ab seropositivity and contact with the cat as a risk factor(P=0.022). Conclusions: The seroprevalence rate of T. gondii infection in pregnant women is relatively low. Consequently, the seronegative pregnant women are at risk, and a considerable rate of positive blood samples for the presence of parasite's DNA should not be ignored. Besides, quantitative real-time PCR could be considered as an accurate method for diagnosis of acute toxoplasmosis especially when the precise results are of the most importance in pregnancy. Limiting contact with cats is also suggested for pregnant women.

Effect of cognitive behavioral therapy on anxiety and depression of infertile women: A meta-analysis

Objective:To investigate the effect of cognitive behavioral therapy on anxiety and depression in infertile women.Methods:This study was performed in 2019 by searching Google Scholar,Scopus,PubMed/MEDLINE,Cochrane library,EMBASE,Proquest,ISI Web of Science,MagIran,SID and IranMedex.Eligible studies were selected by two reviewers and outcomes of interest were extracted.The meta-analysis was performed using the random effect models.Ⅰ-square statistic test was used for heterogeneity analysis.Presence of publication bias was also checked.Results:Eleven studies were included in this review.Between-group differences(cognitive behavioral therapy and control groups)in risk ratio for infertile women's depression was d=-1.36;95%CI=-1.81,-0.90;P<0.001.For infertile women's anxiety,between-group differences in risk ratio wasd=-0.83;95%CI=-1.18,-0.47;P<0.001.Conclusions:Cognitive behavioral therapy is effective in the reduction of depression and anxiety in patients with or withoutin vitro fertilization/intracytoplasmic sperm injection treatment.However,the lack of high-quality studies makes it challenging to make a solid and precise conclusion.Well-designed studies should be undertaken in the future to confirm these results.

Solubility and thermodynamics of lamotrigine in ternary mixtures of ionic liquids([OMIm][Br]+[HMIm][Br]+water)at different temperatures

Experimental mole fraction solubility of lamotrigine(LTG)in ternary aqueous mixtures of two ionic liquids(ILs),1-hexyl and 1-octyl-3-methylimidazolium bromide,[HMIm][Br]and[OMIm][Br]were reported at several temperatures T=(293.15 to 313.15)K.The van’t Hoff and(Jouyban-Acree-van’t Hoff,E-Jouyban-Acree-van’t Hoff,e-NRTL,UNIQUAC and Wilson)models were used to correlate the solubility data.The comparison of the models with temperature and solvent composition dependencies shows that the Wilson model has the minimum ARD which are relatively close to those obtained from Jouyban-Acree-van’t Hoff and E-Jouyban-Acree-van’t Hoff models and maximum ARD belonged to the UNIQUAC model.The order of ARDs for these models is:Wilson b Jouyban-Acree-van’t Hoff,E-Jouyban-Acree-van’t Hoff b e-NRTL b UNIQUAC.Moreover,the apparent thermodynamic functions,Gibbs free energy,enthalpy and entropy of dissolution and mixing were calculated based on the van’t Hoff and Gibbs free energy equations.The strong LTG-ILs interactions and enthalpic contribution of the dissolution process resulted from the calculated thermodynamic functions.

Graphene quantum dot modified glassy carbon electrode for the determination of doxorubicin hydrochloride in human plasma

Low toxic graphene quantum dot（GQD） was synthesized by pyrolyzing citric acid in alkaline solution and characterized by ultraviolet-visible（UV-vis） spectroscopy,X-ray diffraction（XRD）,atomic force microscopy（AFM）,spectrofluorimetery and dynamic light scattering（DLS） techniques.GQD was used for electrode modification and electro-oxidation of doxorubicin（DOX） at low potential.A substantial decrease in the overvoltage（- 0.56 V） of the DOX oxidation reaction（compared to ordinary electrodes） was observed using GQD as coating of glassy carbon electrode（GCE）.Differential pulse voltammetry was used to evaluate the analytical performance of DOX in the presence of phosphate buffer solution（pH 4.0） and good limit of detection was obtained by the proposed sensor.Such ability of GQD to promote the DOX electron-transfer reaction suggests great promise for its application as an electrochemical sensor.

Analysis of human B cell response to recombinant Leishmania LPG3

Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations(2, 10 and 20 μg/m L). B cell activation was assessed through expression of CD69 molecule by flowcytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α(P<0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.

Global prevalence,mortality,and main risk factors for COVID-19 associated pneumocystosis:A systematic review and meta-analysis

Objective:Pneumocystis pneumonia(PcP)is a life-threatening infection caused by the opportunistic fungi Pneumocystis jirovecii.The emergence of the COVID-19 pandemic forced the focus of attention of health policymakers on these two infections due to their clinical and paraclinical similarities,which cause diagnostic dilemmas.This study was undertaken to evaluate and estimate the global prevalence and main leading risk factors of coronavirus-associated pneumocystosis(CAP).Methods:We searched related databases between December 2019 and May 2022 for studies reporting CAP.Meta-analysis was performed using StatsDirect software(version 2.7.9)according to the DerSimonian and Laird method applying the random-effects model.We evaluated heterogeneity using theχ2-based Q statistic(significant for P<0.05)and the I2 statistic(>75%indicative of“notable”heterogeneity).Moreover,an odds ratio(OR)analysis was performed for eligible data.Results:Our meta-analysis included eight studies with 923 patients hospitalized with COVID-19;among them,92 were PcP cases.The overall pooled prevalence of CAP was estimated at 11.5%.The mortality among CAP patients was lower than that of non-PcP patients(OR 1.93;95%CI 0.86-4.31).Long-term corticosteroid therapy(OR 28.22;95%CI 0.54-1480.84)was the most predisposing factor for PcP among COVID-19 patients,followed by pulmonary diseases(OR 1.46;95%CI 0.43-4.98),kidney diseases(OR 1.26;95%CI 0.21-7.49),and acute respiratory destruction syndrome(OR 1.22;95%CI 0.05-29.28).Conclusions:The prevalence of PcP among the COVID-19 population is almost similar to the pre-COVID era.However,PcP-related mortality was decreased by the emergence of the COVID-19 pandemic.Women with COVID-19 are more susceptible to PcP than men.Acute respiratory distress syndrome,kidney diseases,pulmonary diseases,and long-term corticosteroid therapy increased the risk of PcP;however,transplantation and malignancy decreased the risk for PcP among COVID-19 patients.Further retrospective,case-control,prospective,and more precisely systematic review and meta-analysis studies are needed in this field.

Adiponectin Can Affect ER Signaling in Obese Breast Cancer Patients

Background: While the various antitumororal activities of adiponectin as an adipocyte-derived hormone well studied, it is speculated that there is a crosstalk between adiponectin and esterogen receptor (ER) signaling. To test this hypothesis we evaluate the possible correlation between serum level of adiponectin with two estrogen receptors (ERα and ERβ) gene expression in breast cancer patients. Methods: In this case-control study, 70 women with breast cancer participated with different grades of obesity (36 none obese, BMI 2 and 34 obese, BMI ≥ 25 kg/m2).The mean age of Participants was 44.53 yr ± 1.79 yr (21 yr - 70 yr) .Serum level of adiponectin determined by ELISA. Following quantitative expression of estrogen receptors mRNA in tumor tissues was evaluated by Real-time PCR. Results: We find a significant reverse correlation between serum level of Adiponectin and ERα mRNA (r = –0.229, n = 64, p = 0.035) but no correlation was between adiponectin and ERβ in samples (p = 0.228). The lower adiponectin multiplied the odds of having higher ERα mRNA level by a factor of OR = 4.33, 1.28 - 14.6, 95% confidence interval (CI) as compared with those that displayed a moderate or higher serum level of adiponectin (>7.02 ng/ml). The same odds for next estrogen receptor, ERβ, was not greater than unity (OR = 0.31, 0.06 - 1.56, 95% CI). Conclusion: According to the obtained results, it is speculated that as adiponectin can affect ERs gene expression, so affecting the steroid receptor signaling can be proposed as a new underling mechanism of action for this adipokine in breast cancer pathogenesis especially in obese ones.

PPARγ agonist-induced alterations in Δ6-desaturase and stearoyl-CoA desaturase 1:Role of MEK/ERK1/2 pathway

AIM:To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors(PPARγ)agonist-induced alterations in Δ6-desaturase(Δ6D)and stearoyl-CoA desaturase 1(SCD1)in hepatocellular carcinoma cell line HepG2.METHODS:HepG2 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPARγ agonist,pioglitazone.Total RNA was isolated and reverse transcribed from treated cells.Changes in gene expression and metabolites ratio,as activity index for Δ6D and SCD1,were then determined using reverse transcriptionpolymerase chain reaction and gas liquid chromatography,respectively.RESULTS:The expression of both Δ6D(P = 0.03)and SCD1(P = 0.01)increased following PD98059 treatment,with a higher impact on SCD1(24.5%vs 62.5%).Although pioglitazone increased the mRNA level(1.47 ± 0.10 vs 0.88 ± 0.02,P = 0.006)and activity index(1.40 ± 0.07 vs 0.79 ± 0.11,P < 0.001)of Δ6D,no such changes have been observed for SCD1 activity index in pioglitazone-treated cells.SCD1 gene expression(+26.4%,P = 0.041)and activity index(+52.8%,P = 0.035)were significantly increased by MEK inhibition in the presence of pioglitazone,as compared with pioglitazone alone and control cells.However,the response of Δ6D expression and activity index to pioglitazone was unaffected by incubation with PD98059.CONCLUSION:PPARγ and ERK1/2 signaling pathway affect differentially and may have inhibitory crosstalk effects on the genes expression of 6D and SCD1,and subsequently on their enzymatic activities.

Efficient drug and gene delivery to liver fibrosis:rationale, recent advances, and perspectives

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix,and no specific medical therapy is approved for that until now.Due to liver metabolic capacity for drugs,the fragility of drugs,and the presence of insurmountable physiological obstacles in the way of targeting,the development of efficient drug delivery systems for anti-fibrotics seems vital.We have explored articles with a different perspective on liver fibrosis over the two decades,then collected and summarized the information by providing corresponding in vitro and in vivo cases.We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals.Furthermore,the critical chemical and herbal anti-fibrotics,biological molecules such as micro-RNAs,siRNAs,and growth factors,which can affect cell division and differentiation,are mentioned.Likewise,drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables.This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

Effect of vitamin D treatment in children with attention-deficit hyperactivity disorder

Background In this research the symptom improvement of attention-deficit hyperactivity disorder (ADHD) of children was assessed by oral vitamin D administration in Tabriz,Iran.Methods In this double-blind,randomized clinical trials,96 children (2-18 years) were enrolled to placebo and vitamin D groups.Children took vitamin D pearl (50,000 IU/week) or placebo for 6 weeks.Children,who had the change in methylphenidate dosage and received any anticonvulsants and corticosteroids were excluded from the research.ADHD symptoms were diagnosed by Conners parent rating scale (CPRS) test at baseline and after intervention.ADHD Conners divided into inattention (IA),hyperactivity/impulsivity (H/I) and combination type (C) subscales.Vitamin D serum level was assessed at baseline and after 8 weeks in both groups.Results The differences between CPRS and its subscales were not significant at baseline (P > 0.05).The Conners IA score was decreased in vitamin D group (P < 0.05;adjusted with age and baseline values).ADHD Conners and all subscale scores reduced remarkably after intervention in patients with insufficient level of vitamin D compared to placebo (P < 0.05).Conclusions Oral vitamin D improved ADHD symptoms with a particular effect on inattention symptoms.In addition,symptoms related to all subscales were improved remarkably in patients with insufficient level of vitamin D.Vitamin D treatment in children with ADHD could be considered due to the expand benefit of vitamin D in body.

Epigenetic mechanisms as a new approach in cancer treatment:An updated review

Epigenetic,along with genetic mechanisms,is essential for natural evolution and maintenance of specific patterns of gene expression in mammalians.Global epigenetic variation is inherited somatically and unlike genetic variation,it is dynamic and reversible.They are somatically associated with known genetic variations.Recent studies indicate the broad role of epigenetic mechanisms in the initiation and development of cancers,that they are including DNA methylation,histone modifications,nucleosomes changes,non-coding RNAs.The reversible nature of epigenetic changes has led to the emergence of novel epigenetic therapeutic approaches,so that several types of these medications have been approved by the FDA so far.In this review,we discuss the concept of epigenetic changes in diseases,especially cancers,the role of these changes in the onset and progression of cancers and the potential of using this knowledge in designing novel therapeutic strategies.

Polystyrene-graphene oxide modified glassy carbon electrode as a new class of polymeric nanosensors for electrochemical determination of histamine

A simple and rapid protocol for the synthesis of polystyrene-graphene oxide nanocomposite （PS/GONC） was achieved for first time using an in situ polymerization method. PS/GONC modified glassy carbon electrode （PS/GONC/GCE） has been employed as an efficient nanosensor for the electrooxidation of histamine. The PS/GONC/GCE is used as an electrochemical nanosensors for monitoring histamine using differential pulse voltammetry techniques （detection limit 0.03 μmol/L）. In addition, the prepared nanosensor was successfully applied to determine histamine in fish samples, yielding satisfactory results. The spiked recoveries were in the range of 98.2%-103.1%.

Cancer stem cell-targeted chimeric antigen receptor(CAR)-T cell therapy: Challenges and prospects

Cancer stem cells(CSCs)with their self-renewal ability are accepted as cells which initiate tumors.CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies,including radiotherapy and chemotherapy.Chimeric antigen receptor(CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens(TAAs)by which they accurately target and kill cancer cells.In recent years,CAR-T cell therapy has shown more efficiency in cancer treatment,particularly regarding blood cancers.The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy.Here we review the CSC markers that have been previously targeted with CAR-T cells,as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future.Furthermore,we will detail the most important obstacles against CART cell therapy and suggest solutions.

Effect of incorporating Elaeagnus angustifolia extract in PCL-PEG-PCL nanofibers for bone tissue engineering

Plants have been used for medicinal purposes for thousands of years but they are still finding new uses in modem times. For example, Elaeagnus angustifolia (EA) is a medicinal herb with antinociceptive, anti-inflammatory, antibacterial and antioxidant properties and it is widely used in the treatment of rheumatoid arthritis and osteoarthritis. EA extract was loaded onto poly(ε-caprolactone)- poly(ethylene glycol)-poly(ε-caprolactone)(PCLPEG-PCL/EA) nanofibers and their potential applications for bone tissue engineering were studied. The morphology and chemical properties of the fibers were evaluated using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, contact angle measurements and mechanical tests. All the samples had bead-free morphologies with average diameters ranging from 100 to 200 nm. The response of human cells to the PCL-PEGPCL/ EA nanofibers was evaluated using human dental pulp stem cells (hDPSCs). The hDPSCs had better adhesion and proliferation capacity on the EA loaded nanofibers than on the pristine PCL-PEG?PCL nanofibers. An alizarin red S assay and the alkaline phosphatase activity confirmed that the nanofibrous scaffolds induced osteoblastic performance in the hDPSCs. The quantitative real time polymerase chain reaction results confirmed that the EA loaded nanofibrous scaffolds had significantly upregulated gene expression correlating to osteogenic differentiation. These results suggest that PCL-PEG-PCL/ EA nanofibers might have potential applications for bone tissue engineering.

Natural products,PGC-1α,and Duchenne muscular dystrophy

Peroxisome proliferator-activated receptorγ(PPARγ)is a transcriptional coactivator that binds to a diverse range of transcription factors.PPARγcoactivator 1(PGC-1)coactivators possess an extensive range of biological effects in different tissues,and play a key part in the regulation of the oxidative metabolism,consequently modulating the production of reactive oxygen species,autophagy,and mitochondrial biogenesis.Owing to these findings,a large body of studies,aiming to establish the role of PGC-1 in the neuromuscular system,has shown that PGC-1 could be a promising target for therapies targeting neuromuscular diseases.Among these,some evidence has shown that various signaling pathways linked to PGC-1αare deregulated in muscular dystrophy,leading to a reduced capacity for mitochondrial oxidative phosphorylation and increased reactive oxygen species(ROS)production.In the light of these results,any intervention aimed at activating PGC-1 could contribute towards ameliorating the progression of muscular dystrophies.PGC-1αis influenced by different patho-physiological/pharmacological stimuli.Natural products have been reported to display modulatory effects on PPARγactivation with fewer side effects in comparison to synthetic drugs.Taken together,this review summarizes the current knowledge on Duchenne muscular dystrophy,focusing on the potential effects of natural compounds,acting as regulators of PGC-1α.

Contribution of Water and Lipid Soluble Substances in the Relaxant Effects of Tymus Vulgaris Extract on Guinea Pig Tracheal Smooth Muscle in Vitro

Objective： To examine the relaxant effects of hydro-ethanolic, macerated aqueous （MA） and lipid- free macerated aqueous （LFMA） extract of Tymus vulgaris on tracheal chains of guinea pigs. Methods： The relaxant effects of five cumulative concentrations of each extract （0.4, 0.8, 1.2, 1.6 and 2.0 g/100 mL） were compared with saline as negative control and five cumulative concentrations of theophylline （0.1, 0.2, 0.4, 0.6 and 0.8 mmol/L） on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCl （group 1） and 10 μmol/L methacholine （group 2, n=6 for each group）. Results： In group 1 all concentrations of theophylline, three higher concentrations of hydro-ethanolic, two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline （P〈0.05 or P〈0.01）. Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline （P〈0.05 or 0.01）. In group 2 experiments, all concentrations of theophylline, hydro-ethanolic, MA and LFMA extracts showed significant relaxant effects compared to that of saline （P〈0.05 or P〈0.01）. In both groups, the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others （P〈0.05 or P〈0.01）. The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments （all P〈0.01）. There were significantly positive correlations between the relaxant effects and concentrations for theophylline and all extracts in both groups （P〈0.05 or P〈0.01）. Conclusion： Hydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.

The safety perspective of probiotic and non-probiotic yoghurts:a review

Objectives:Milk and dairy products could be contaminated via various bacteria and fungi.Investigations have demonstrated that the contamination in traditionally yoghurt was higher than industrially processed one.Raw milk with neutral pH and high water activity,serves as an excellent growth medium for different microorganisms,Therefore,the prepared yoghurts may be contaminated.The greatest and most widespread concern of yoghurt safety is microbial contamination,the presence of infectious bacteria and viruses.Materials and Methods:“Probiotic yoghurt”was uses as key word in PubMed and science direct search engines during 1998-2018 and 70 papers were found and forty of them were used in this study.Results:Existence of yeasts and molds in industrial yoghurt is an indicative of poor hygienic practices in manufacturing and packaging.Aflatoxins are a group of very toxic metabolites of fungi produced by toxicogenic strains of Aspergillus flavus,Aspergillus parasiticus and Aspergillus nomius in milk and dairy products.Aflatoxin B1 is the most frequent produced mycotoxin in contaminated yoghurt.There is a direct relationship between the AFM1 presences in yoghurt the risk of illnesses in consumers.Conclusions:In conclusion,it is important to notify producers and consumers about the safety and contamination of yoghurt in order to reduce their potential health hazard and economic issues.With respect to the safety and health effects of probiotics,it is recommended to consume the probiotic yoghurt.