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.

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in TC.Additionally,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be discussed.This review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly MTC.Additionally,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and described.MiRNAs can perform as oncomiRs or antioncoges,relying on the target mRNAs they regulate.MiRNA replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in cancer.MiRNAs are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair pathways.MiRNAs are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as well.MiRNAs have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic targets.The contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

Molecular Detection of <i>Anaplasma</i>and <i>Ehrlichia</i>Infection in Ticks in Borderline of Iran-Afghanistan

Anaplasmosis, a disease caused by various species of Anaplasma, poses important economic constraints to animal breeders. Ehrlichiosis is a worldwide zoonosis illness and mostly occurs in tropical and subtropical regions that are close to the vector’s distribution. Tick-borne pathogens lead to over 100,000 cases of illness in the world each year. Besides the costs of the additional veterinary care, anaplasmosis causes abortion in animals, reduction of milk production, body weight, and frequently leads to death. In this study, we investigated on infection of ticks to Anaplasma and Ehrlichia pathogens in Zabol and Zahak County in Sistan and Baluchestan Province where is bordered with Afghanistan. Totally from June 2013 to May 2014, 369 ticks were caught from goats, cows and sheep. Molecular studies on 53 of these samples which represented all specimens, showed that Ehrlichia’s DNA and Anaplasma’s DNA was found in 14 (26.4%) out of the 53 selected specimens. The results showed the infection of Rhipicephalus sanguineus and Hyalomma anatolicum with Anaplasma ovis. Also we saw infection of H. anatolicum and H. asiaticum ticks to Ehrlichia spp. This study has been intended to do a comprehensive survey of Ehrlichia and Anaplasma distribution in ticks caught from east of Iran;it was designed to investigate the presence of Anaplasma spp. and Ehrlichia spp. in Zabol and Zahak Counties, Iran. These results show that these pathogens should be controlled in such regions.

Self-Healing MXene-and Graphene-Based Composites:Properties and Applications

Today,self-healing graphene-and MXene-based composites have attracted researchers due to the increase in durability as well as the cost reduction in long-time applications.Different studies have focused on designing novel self-healing graphene-and MXenebased composites with enhanced sensitivity,stretchability,and flexibility as well as improved electrical conductivity,healing efficacy,mechanical properties,and energy conversion efficacy.These composites with self-healing properties can be employed in the field of wearable sensors,supercapacitors,anticorrosive coatings,electromagnetic interference shielding,electronic-skin,soft robotics,etc.However,it appears that more explorations are still needed to achieve composites with excellent arbitrary shape adaptability,suitable adhesiveness,ideal durability,high stretchability,immediate self-healing responsibility,and outstanding electromagnetic features.Besides,optimizing reaction/synthesis conditions and finding suitable strategies for functionalization/modification are crucial aspects that should be comprehensively investigated.MXenes and graphene exhibited superior electrochemical properties with abundant surface terminations and great surface area,which are important to evolve biomedical and sensing applications.However,flexibility and stretchability are important criteria that need to be improved for their future applications.Herein,the most recent advancements pertaining to the applications and properties of self-healing graphene-and MXene-based composites are deliberated,focusing on crucial challenges and future perspectives.

Ivermectin as an adjunct treatment for hospitalized adult COVID-19 patients: A randomized multi-center clinical trial

Objective: To evaluate different doses of ivermectin in adult patients with mild COVID-19 and to evaluate the effect of ivermectin on mortality and clinical consequences.Methods: A randomized, double-blind, placebo-controlled, multicenter clinical trial was performed at five hospitals. A total of 180 mild hospitalized patients with COVID-19 confirmed by PCR or chest image tests were enrolled and allocated to six arms including hydroxychloroquine 200 mg twice per day, placebo plus hydroxychloroquine 200 mg twice per day, single dose ivermectin(200 μg/kg), three low interval doses of ivermectin(200, 200, 200 μg/kg), single dose ivermectin(400 μg/kg), and three high interval doses of ivermectin(400, 200, 200 μg/kg). The primary endpoint of this trial was all-cause of mortality or clinical recovery. The radiographic findings, hospitalization and low O_2 saturation duration, and hematological variables of blood samples were analyzed. Results: A total of 16.7%(5/30) and 20.0%(6/30) patients died in arms treated with hydroxychloroquine 200 mg twice per day and placebo plus hydroxychloroquine 200 mg twice per day, respectively, and a reduction in mortality rate in patients receiving ivermectin treatment to 0%, 10%, 0% and 3.3% for arms 1-4 were observed. Risk of mortality was also decreased about 15% in the ivermectin treated arms. Conclusions: Ivermectin as an adjunct reduces the rate of mortality, time of low O_2 saturation, and duration of hospitalization in adult COVID-19 patients. The improvement of other clinical parametersshows that ivermectin, with a wide margin of safety, had a high therapeutic effect on COVID-19.

Cytokine changes and embryo attachment in mouse endometrial cells following treated with peripheral blood mononuclear cells(PBMCs)expressing ectopic hCG,and hCG-activated PBMCs

Objective:To compare the effect of human chorionic gonadotropin(hCG)-producing peripheral blood mononuclear cells(PBMCs)and PBMCs activated by hCG in vitro and expressions of related immune genes in mouse implantation.Methods:hCG-producing PBMCs(transfected PBMC)and PBMCs activated by hCG in vitro were introduced into isolated mouse endometrial cells,while cell cultures were divided into four groups:the control,PBMC,transfected,and activated PBMC groups.The expression of studied genes(IL-1β,IL-6,Lif,and Vegf)was evaluated and blastocyst attachment on the cocultured cells(isolated endometrial cells and PBMC cells)was monitored in all four groups.Results:Data showed that expression decreased in the PBMC group compared to the treated PBMC(transfected and activated PBMCs)and increased in transfected PBMC compared to the activated PBMC.Attachment and migration of blastocysts were dramatically enhanced in the transfected PBMC group compared to the activated PBMC group(P<0.05).Conclusions:Use of hCG-producing PBMCs(transfected PBMC)has more influence on endometrial receptivity.

Exosomes in viral infection:Effects for pathogenesis and treatment strategies

Exosomes are small vesicles that carry molecules from one cell to another.They have many features that make them interesting for research,such as their stability,low immunogenicity,size of the nanoscale,toxicity,and selective delivery.Exosomes can also interact with viruses in diverse ways.Emerging research highlights the significant role of exosomes in viral infections,particularly in the context of diseases like COVID-19,HIV,HBV and HCV.Understanding the intricate interplay between exosomes and the human immune system holds great promise for the development of effective antiviral therapies.An important aspect is gaining clarity on how exosomes influence the immune system and enhance viral infectivity through their inherent characteristics.By leveraging the innate properties of exosomes,viruses exploit the machinery involved in exosome biogenesis to set replication,facilitate the spread of infection,and eliminate immune responses.They can either help or hinder viral infection by modulating the immune system.This review summarizes the recent findings on how exosomes mediate viral infection and how they can be used for diagnosis or therapy.This could lead to new clinical applications of exosomes in disease management.

Mesenchymal stem cell secretome: A promising therapeutic strategy for erectile dysfunction?

Objective:The secretome,comprising bioactive chemicals released by mesenchymal stem cells(MSCs),holds therapeutic promise in regenerative medicine.This review aimed to explore the therapeutic potential of the MSC secretome in regenerative urology,particularly for treating erectile dysfunction(ED),and to provide an overview of preclinical and clinical research on MSCs in ED treatment and subsequently to highlight the rationales,mechanisms,preclinical investigations,and therapeutic potential of the MSC secretome in this context.Methods:The review incorporated an analysis of preclinical and clinical research involving MSCs in the treatment of ED.Subsequently,it delved into the existing knowledge regarding the MSC secretome,exploring its therapeutic potential.The methods included a comprehensive examination of relevant literature to discern the processes underlying the therapeutic efficacy of the MSC secretome.

Kaempferol attenuates cognitive deficit via regulating oxidative stress and neuroinflammation in an ovariectomized rat model of sporadic dementia

Alzheimer＇s disease（AD） is associated with oxidative stress, and ultimately results in cognitive deficit. Despite existing literature on the pathophysiology of AD, there is currently no cure for AD. The present study investigated the effects of kaempferol（Kmp） isolated from the extract of Mespilus germanica L.（medlar） leaves on cognitive impairment, hippocampal antioxidants, apoptosis, lipid peroxidation and neuro-inflammation markers in ovariectomized（OVX） rat models of sporadic AD. Kaempferol, as the main flavonoid of medlar extract has been previously known for anti-oxidative, anti-inflammatory and anti-neurotoxic effects. Thirty-two female Wistar rats were ovariectomized, and randomly divided into four groups： sham, OVX ＋ saline, OVX ＋ streptozotocin（STZ） ＋ saline, OVX ＋ STZ ＋ Kmp. Animals received intracerebroventricular injection of STZ（3 mg/kg, twice with one day interval） to establish models of sporadic AD. Intraperitoneal injection of Kmp（10 mg/kg） for 21 days was performed in the OVX ＋ STZ ＋ Kmp group. Spatial learning and memory of rats were evaluated using a Morris water maze. Finally, brain homogenates were used for biochemical analysis by enzyme-linked immunosorbent assay. The results showed a significant improvement in spatial learning and memory as evidenced by shortened escape latency and searching distance in Morris water maze in the OVX ＋ STZ ＋ Kmp group compared with the OVX ＋ STZ group. Kmp also exhibited significant elevations in brain levels of antioxidant enzymes of superoxide dismutase and glutathione, while reduction in tumor necrosis factor-α and malondialdehyde. Our results demonstrate that Kmp is capable of alleviating STZ-induced memory impairment in OVX rats, probably by elevating endogenous hippocampal antioxidants of superoxide dismutase and glutathione, and reducing neuroinflammation. This study suggests that Kmp may be a potential neuroprotective agent against cognitive deficit in AD.

The potential of miR-183 family expression in inner ear for regeneration,treatment,diagnosis and prognosis of hearing loss

miRNA-183 family, in normal biology, is expressed in a harmonious and stable manner in the neurosensory organs and cells. Studies have also shown that miRNA-183 family, in different pathways, affects the neurosensory development, maintenance, survival and function. In addition, it has potential neuroprotective effects in response to neurosensory destructive stimulations. miRNA-96 mutation causes hereditary deafness in humans and mice, and therefore affects the inner ear activity and its maintenance. Certain roles have been identified for mi R-96 in the maintenance and function of the inner ear. The comparison of the target genes of family-183 in transcriptomes of newborn and adult hair cells shows that hundreds of target genes in this family may affect development and maintenance of the ears. Identifying the genes that are regulated by miRNA-183 family provides researchers with important information about the complex development and environmental regulation of the inner ear, and can offer new approaches to the maintenance and regeneration of hair cells and auditory nerve.

Rat hair follicle stem cells differentiate and promote recovery following spinal cord injury

Emerging studies of treating spinal cord injury （SCI） with adult stem cells led us to evaluate the effects of transplantation of hair follicle stem cells in rats with a compression-induced spinal cord lesion. Here, we proposed a hypothesis that rat hair follicle stem cell transplantation can promote the recovery of injured spinal cord. Compression-induced spinal cord injury was induced in Wistar rats in this study. The bulge area of the rat vibdssa follicles was isolated, cultivated and characterized with nestin as a stem cell marker. 5-Bromo-2＇-deoxyuridine （BrdU） labeled bulge stem cells were transplanted into rats with spinal cord injury. Immunohistochemical staining results showed that some of the grafted cells could survive and differentiate into oligodendrocytes （receptor-interacting protein positive cells） and neuronal-like cells （~lll-tubulin positive cells） at 3 weeks after transplantation. In addition, recovery of hind limb locomotor function in spinal cord injury rats at 8 weeks following cell transplantation was assessed using the Basso, Beattie and Bresnahan （BBB） locomotor rating scale. The results demon- strate that the grafted hair follicle stem cells can survive for a long time period in vivo and differentiate into neuronal- and glial-like cells. These results suggest that hair follicle stem cells can promote the recovery of spinal cord injury.

Circulation of Brucellaceae,Anaplasma and Ehrlichia spp.in borderline of Iran,Azerbaijan,and Armenia

Objective:To estimate the infection of ticks to Anaplasma,Ehrlichia,Babesia,Theileria,and Brucellaceae using molecular methods in borderline of Iran,Azerbaijan,and Armenia.Methods:Totally,2022 ticks were collected from different livestock.Then,species were diagnosed under stereomicroscope according to valid morphological keys.Tick DNA was extracted followed by PCR to detect Anaplasma,Ehrlichia,Theileria,Babesia and Brucellaceae infection in ticks.Results:A total of 498 males[24.62%(95%CI 22.76%-26.57%)],741 females[36.64%(95%CI 34.54%-38.79%)],782 nymphs[38.67%(95%CI 36.55%-40.84%)]and 1 larva[0.04%(95%CI 0.00%-0.28%)]were identified.Among identified samples,we found four genera including Hyalomma,Rhipicephalus,Haemaphysalis,and Dermacentor.Molecular assay revealed that the prevalence of ticks to Anaplasma or Ehrlichia,and Brucellaceae was 22.02%(95%CI 16.01%-29.06%)and 15.03%(95%CI 9.43%-22.26%),respectively.Phylogenetic analysis showed that the identified Anaplasma sp.had the most similarity with Anaplasma centrale,Anaplasma platys,Anaplasma camelii,and Anaplasma phagocytophilum,submitted in GenBank.Furthermore,the detected Ehrlichia sp.and Brucellaceae bacterium had the most similarity with Ehrlichia ruminantium and Mycoplana peli,respectively.However,no sign of the presence of Theileria and Babesia spp.was seen in the studied samples.Conclusions:Anaplasmosis,ehrlichiosis and brucellosis should be considered as important health threats in northwestern Iran and consistent monitoring on infection of ticks and livestock should be performed regularly.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

Legionella and legionnaires' disease: An overview

Legionellosis is the generic term used to describe infections caused by different varieties of Legionella spp.,including Legionnaires'disease(LD),a severe and potentially fatal form of pneumonia,and Pontiac fever,a self-limited flu-like illness.Legionellosis is usually acquired through inhalation or aspiration of aerosols containing Legionella spp.These bacteria can cause acute consolidating pneumonia in susceptible patients who are at an advanced age,have underlying debilitating diseases,or are immunodeficient.The main natural reservoir for Legionella is water and this pathogen colonizes many different natural and man-made freshwater environments such as water networks,cooling towers,and water systems in buildings and hospitals.In recent years,various laboratory diagnostic tests for Legionella infections have changed significantly.Although the sequencing method is nowadays considered the fastest and most reliable method for differentiation and detection of different Legionella species,the isolation of these bacteria from clinical specimens is the golden standard for diagnosis of Legionnaires'disease.Today the urinary antigen test as the most rapid and inexpensive method is routinely used for diagnosis of LD caused by Legionella pneumophila serogroup 1.The macrolides and fluoroquinolones are still the mainstays for the treatment of Legionella infections.For the prevention of spreading the contaminated water aerosols and controlling Legionella infections,an effective water treatment procedure is necessary.This review describs and summarizes the latest available information about all aspects of Legionella and Legionnaires'disease.

Elevated serum nitric oxide and hydrogen peroxide levels as potential valuable predictors of herpes zoster

Objective:To evaluate the biomarkers of oxidative stress in herpes zoster patients compared with control subjects.Methods:This study compared the nitric oxide(NO),hydrogen peroxide(H2 O2),malon dialdehyde,uric acid,and bilirubin levels between 43 herpes zoster patients and 47 age-matched control subjects.The area under the curve of the receiver operating characteristic curve was performed to evaluate the final logistic regression model.Results:The significant differences were observed in the serum levels of NO,H2 O2,and malondialdehyde between the case and the control groups(P<0.001).However,no statistical differences were found in both uricacid and bilirubin levels between the groups.Additionally,the raised oxidant biomarkers were strongly associated with increased disease severity(P<0.001).Multiple logistic regression analysis with the highest area under the curve[0.98(95%CI 0.95-1.00)]and the minimum number of variables showed that high levels of NO(OR 1.24;95%CI 1.06-1.46;P=0.008)and H2 O2(OR 1.25;95%CI 1.09-1.43;P=0.001)were associated with herpes zoster.Conclusions:High levels of NO and H2 O2 were observed in patients with herpes zoster.Increased NO and H2 O2 levels might be associated with herpes zoster,which needs to be confirmed by further studies.

Preliminary study on association between toxoplasmosis and breast cancer in Iran

Objective:To investigate the possible association between Toxoplasma gondii(T.gondii)infection and breast cancer by examining the seropositivity and serointensity rate of anti-T gondii antibodies in breast cancer patients and healthy volunteers.Methods:This study was carried out on 66 women with breast cancer which consists of 29 newly diagnosed patients(Group 1) and 37 cases undergoing treatment and regular checkups(Group 2).Also,60 healthy women(Group 3) with no history of cancer confirmed by clinical examination and imaging participated in this study.The participants were tested for T.gondii immunoglobulin G(IgG) and immunoglobulin M(IgM) antibodies by enzyme-linked immunoassays.Results:The mean age of Groups 1.2 and 3 were 43.3±6.8,41.8±5.5 and 42.3±4.9.respectively(P=0.72).Overall.104(82.5%) and 8(6.3%) out of 126 women were positive for anti-T gondii IgG and IgM antibodies,respectively.Higher seropositivity rate of anti-T.gondii antibodies(IgG) was seen in breast cancer patients(86.4%) compared with control group(78.3%)(P=0.24).IgG antibodies were detected in 89.2%of cancer patients under treatment.82.7%of newly diagnosed patients(P=0.18).IgM antibodies were found in 3(10.3%),2(5.4%)and 3(5%) in Groups 1.2 and 3.No significant difference was found between the mean titers of T.gondii IgG antibody among these groups(P=0.87).Conclusions:This study did not find any significant association between toxoplasmosis and breast cancer besides higher rates of seropositivity and serointensity in patients compared with healthy volunteers.

Molecular characterization of Echinococcus granulosus in paraffin-embedded human tissues from Southwest Iran

Objective:To investigate Echinococcus(E.)granulosus genotypes as the causative agents of hydatidosis in humans in the southwest of Iran(Khuzestan province).Methods:In this study,isolates of 80 archived human paraffin embedded hydatid cysts were collected from pathology laboratories in Ahvaz city,Khuzestan province.DNA was extracted and examined by nested-PCR of ribosomal DNA(rDNA)internal transcribed spacer 1(ITS1),and PCR-RFLP.In addition,the sequences of fragments of genes coding for Cox space1 and NADH dehydrogenase 1(ND1)were also examined.Results:Of the 80 paraffin samples,44(55.0%)were from the liver,27(33.8%)from the lung,and the rest from other organs.The amplified hydatid genomic DNA showed that the cysts were E.granulosus strains.The results of PCR-RFLP and sequencing analysis revealed the presence of G1 genotype(sheep strain)in all human isolates.Furthermore,no camel strain(G6)was detected among all samples in the regions studied.Conclusions:The molecular findings indicate that the predominant genotype involved in E.granulosus transmission in southwest of Iran is the common sheep strain(G1),which occurs in human populations.These results may have important implications for hydatid disease control in the studied areas.

Association between Pri-miR-34b/c rs4938723 polymorphism and bladder cancer risk

Several studies examined the impact of miR-34b/c rs4938723 polymorphism and cancer risk, but the findings are inconsistent. However, no study has been conducted to inspect the impact of miR-34b/c polymorphism on bladder cancer. This study aimed to assess possible association between rs4938723 polymorphism and bladder cancer risk.This case-control study was done on 136 pathologically proven bladder cancer patients and 144 controls. Genotyping of Pri-miR-34b/c rs4938723 polymorphism was achieved by using the polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP) method. Our findings did not show any statistically significant differences in genotype and allele frequencies between bladder cancer and controls. Larger sample sizes with diverse ethnicities are required to validate our findings.

Sustained small and intermediate size proteins expression in phorbol 12-myristate 13-acetate/ionomycine prolonged stimulated human fibroblasts

Objective:To compare the protein profile of culture supernatants in stimulated and unstimulated human fibroblasts to find some proteins indicating the presence of fibroblasts and their activation status.Methods:Dermal fibroblasts were stimulated with phorbol 12-myristate 13-acetate(PMA)/ionomycine for 72 h.MTT assay was done to determine cell viability and A/E fluorescent staining was used to evaluate the cell death pattern.Protein analysis was performed by gradient SDS polyacrylamide gel electrophoresis 8%–16%.Results:The supernatant of 24 h cultured both stimulated and unstimulated fibroblasts showed two bands in SDS-PAGE analysis with relative molecular weights of 8.59 and78.8 k Da.These bands density was decreased during the next 48 h in unstimulated cells while their expression was continued in PMA or PMA/ionomycine stimulated cells and a new 85.3 k Da band was appeared in unstimulated and 72 h PMA stimulated cells.Moreover,we found another seven small size(10–19.5 k Da) proteins in supernatants of48 h and 72 h unstimulated but not in PMA or PMA/Ionomycine stimulated fibroblasts.Most of these proteins expression were down regulated following fibroblast activation.This down-regulation is consistent with our finding that PMA or PMA/ionomycine stimulated cells exhibited a significant level of apoptosis cell death.Conclusions:Human fibroblasts produce some small to intermediate sized proteins with specific SDS-PAGE profile upon cell activation.Most of these proteins can be excreted in urine and can be immunogen theoretically so this data provided a reliable clue for fibrosis biomarker screening based on designation of an appropriated immunoassay.