Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retinaderived RPE cell line

AIM:To evaluate the effect of auraptene(AUR)treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor(VEGF)-A and platelet-derived growth factors(PDGFs)in human retinal pigment epithelium(RPE)cell line.METHODS:Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80.RPE cell line was treated with both free AUR and niosome-encapsulated.Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Expression of VEGF-A and PDGF-A,PDGF-B,PDGF-C,PDGF-D genes was measured after total RNA extraction and cDNA synthesis,using real-time polymerase chain reaction(RT-PCR).RESULTS:The highest entrapment efficiency(EE)was achieved by Span 60:cholesterol(1:1)with 64.3%.The half maximal inhibitory concentration(IC50)of free and niosome-encapsulated AUR were 38.5 and 27.78µg/mL,respectively.Release study revealed that niosomal AUR had more gradual delivery to the cells.RT-PCR results showed reduced expression levels of VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D after treatment with both free and niosomal AUR.CONCLUSION:Niosomal formulation of Span 60:cholesterol(1:1)is an effective drug delivery approach to transfer AUR to RPE cells.VEGF-A,PDGF-A,PDGF-B,PDGF-C,and PDGF-D are four angiogenic factors,inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

Impact of umbelliprenin-containing niosome nanoparticles on VEGF-A and CTGF genes expression in retinal pigment epithelium cells

AIM:To investigate the impact of niosome nanoparticles carrying umbelliprenin(UMB),an anti-angiogenic and anti-inflammatory plant compound,on the expression of vascular endothelial growth factor(VEGF-A)and connective tissue growth factor(CTGF)genes in a human retinal pigment epithelium(RPE)-like retina-derived cell line.METHODS:UMB-containing niosomes were created,optimized,and characterized.RPE-like cells were treated with free UMB and UMB-containing niosomes.The IC_(50)values of the treatments were determined using an MTT assay.Gene expression of VEGF-A and CTGF was evaluated using real-time polymerase chain reaction after RNA extraction and cDNA synthesis.Niosomes’characteristics,including drug entrapment efficiency,size,dispersion index,and zeta potential were assessed.Free UMB had an IC_(50)of 96.2μg/mL,while UMB-containing niosomes had an IC_(50)of 25μg/mL.RESULTS:Treatment with UMB-containing niosomes and free UMB resulted in a significant reduction in VEGF-A expression compared to control cells(P=0.001).Additionally,UMB-containing niosomes demonstrated a significant reduction in CTGF expression compared to control cells(P=0.05).However,there was no significant reduction in the expression of both genes in cells treated with free UMB.CONCLUSION:Both free UMB and niosome-encapsulated UMB inhibits VEGF-A and CTGF genes expression.However,the latter demonstrates significantly greater efficacy,potentially due to the lower UMB dosage and gradual delivery.These findings have implications for anti-angiogenesis therapeutic approaches targeting age-related macular degeneration.

Expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients:A retrospective study

Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.

Fauna and some biological characteristics of Anopheles mosquitoes(Diptera:Culicidae) in Kalaleh County,Golestan Province,northeast of Iran

Objective:To determine fauna and some ecological aspects of Anopheles mosquitoes in northeast of Iran.Methods:In this descriptive study,3 villages in Kalaleh County were selected in different geographical zones.Anopheles mosquitoes were collected biweekly from May to October using standard dipping method for larvae,and hand catch,total catch,artificial pit shelter as well as night-biting collections on human and animal baits for adults.Results:Totally 399 larvae and 2 602 adults of Anopheles mosquitoes were collected and identified as 2 species:Anopheles superpictus s.l.(An.superpictus s.l.) and Anopheles maculipennis s.l.The dominant species was An.superpictus s.l.(92.1%).Activity of these mosquitoes found to be started from middle of May and extended till September with two peaks of activity in July and August.Conclusions:An.superpictus s.l.as one of the main malaria vectors in Iran as well as some other parts of the world is the dominant species in the study area.This species has high potential for transmission and possibility of establishing a transmission cycle with low abundance.Other species,Anopheles maculipennis s.l.also has introduced as a malaria vector in northern parts of Iran.As this Anopheles is a complex species,genetic studies are recommended to determine the members of this complex in the study area.

The Relationship between Quality of Life with Demographic Variables of Elderly in Golestan Province-Iran

Quality of life subscales was influenced by different factors including age, gender, and financial status and more importantly by health, education, financial and marital status. The main goal of this study was relationship between (QOL) with demographic variables of elderly in Golestan province-Iran. This research was an analytical cross study that conducted on 193 individuals going to Jahandidegan geriatric charity institution of Golestan-Iran. The data were collected from questionnaire SF-36 for QOL the elderly indicators through interviews and observation and then analyzed using SPSS V.17 Software. Among QOL dimensions, only general health status showed a significant association with supporting organizations covering status (P = 0.01). The relationship between QOL with current employment status in both genders was observed.

Study of Hepatitis B Virus Genotypes and Mutation in 1762 &1764 Nucleotides of X Gene in Chronic HBV Patients from Golestan Province—Iran

Introduction: More than 350 million people are chronic carriers of HBV and many of them develop progressive diseases, including cirrhosis and hepatocellular carcinoma. Many of those infected develop persistent disease and a proportion goes on to develop liver failure and cancer. Researchers showed that double mutations of the x gene at position 1762 and 1764, have been found in chronic hepatitis B. These mutations were proposed to be associated with fulminant hepatitis B increasing risk of hepatocellular carcinoma. This project aimed to investigate mutation in the x gene region of HBV infected patients in Golestan province, Iran. Method: 100 patients were entered in this study. Hepatitis B viral DNA was extracted from plasma and PCR was performed using specific primers. Direct sequencing and alignment of x gene were applied using reference sequence from Gene Bank database (Okamoto, 1988;Accession number AB033559). Results: Among the chronic HBV patients 51% were male. The results showed that 49% of patients had A1762T, G1764A mutations changing AGG to stop codon TGA. 27% and 24% of cases were showed mutation only in A1762T and G1764A positions respectively. Conclusion: This study was shown presence of X gene mutation in HBV infected people in Golestan province, Iran. The rate of mutation in two positions 1762 and 1764 of HBV genotype D X gene was higher than the average rate of the world (34%).

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers

BACKGROUND Systemic lupus erythematosus(SLE)is a chronic autoimmune disorder impacting multiple organs,influenced by genetic factors,especially those related to the immune system.However,there is a need for new biomarkers in SLE.MicroRNA-125a(miR-125a)levels are decreased in T cells,B cells,and dendritic cells of SLE patients.MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha(TNF-α)and interleukin 12(IL-12),which are crucial pro-inflammatory cytokines in SLE pathogenesis.AIM To assess the levels of miR-125a,IL-12,and TNF-αin SLE patients’plasma,evaluating their diagnostic and prognostic value.METHODS The study included 100 healthy individuals,50 newly diagnosed(ND),and 50 SLE patients undergoing treatment.The patients were monitored for a duration of 24 wk to observe and record instances of relapses.MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction,while ELISA kits were used to assess IL-12 and TNF-αproduction.RESULTS The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals,with the lowest levels in ND patients.TNF-αand IL-12 expression levels were significantly elevated in SLE patients,especially in the early stages of the disease.Receiver operating characteristic curve analyses,and Cox-Mantel Log-rank tests indicated miR-125a,TNF-α,and IL-12 as proper diagnostic biomarkers for SLE.A negative correlation was found between plasma miR-125a expression and IL-12/TNF-αlevels in SLE patients.CONCLUSION Decreased miR-125a levels may be involved in the development of SLE,while elevated levels of IL-12 and TNF-αcontribute to immune dysregulation.These findings offer new diagnostic and prognostic markers for SLE.Moreover,the negative correlation observed suggests an interaction between miR-125a,TNF-α,and IL-12.Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Inoperable esophageal cancer and outcome of palliative care

AIM:To determine the outcome of esophageal cancer patients referred for palliative care,in Gorgan and Gonbad gastrointestinal clinics,northeast of Iran. METHODS:This cross-sectional study was done on inoperable esophageal cancer cases referred to gastrointestinal clinics in Gorgan and Gonbad city(2005-2006) . Demographic data were collected during the procedure and cases were followed up every one month. Improvement proportion was calculated with 95% confidence interval,to determine the rate of improvement. Survival analysis and Kaplan-Meier methods were used to estimate the duration of palliative care effectiveness. RESULTS:We recruited 39 cases into the study. Squamous cell carcinoma was the most prevalent(92.3%) . The middle third of the esophagus was involved predominantly(51.3%) . Dilation was the most preferred method(89.7%) and stenting was done in 4 cases. Decreasing dysphagia score was not related to palliation method or pathology type of carcinoma. Age of the patients was significantly related to the improvement of dysphagia score. Mean survival time was 137.6 d and median was 103 d. CONCLUSION:Results of this study showed a low survival rate after palliative care in esophageal cancer cases despite dysphagia scores' improvement after dilating or stenting.

An overview on application of phage display technique in immunological studies

Phage display is very strong technique in drug discovery and development. Phage display has many applications in improving the immunological studies. Development of monoclonal antibody, peptides, peptidomimetics and epitope mapping are main application of phage display. Selection of monoclonal antibody or peptides that are displayed on the surface of the phages can be occurred through biopanning process. In biopanning process phage library is incubated with antigen and particular phages can be identified and isolated. Increasing the stringency in the biopanning rounds can be help to select phages with high affinity and specificity. Here, we describe an overview of phage display application with focusing on monoclonal antibody production and epitope mapping.

Ankylosing spondylitis: A state of the art factual backbone

Ankylosing spondylitis(AS) is a chronic inflammatory disease that affects 1% of the general population. As one of the most severe types of spondyloarthropathy, AS affects the spinal vertebrae and sacroiliac joints, causing debilitating pain and loss of mobility. The goal of this review is to provide an overview of AS, from the pathophysiological changes that occur as the disease progresses, to genetic factors that are involved with its onset. Considering the high prevalence in the population, and the debilitating life changes that occur as a result of the disease, a strong emphasis is placed on the diagnostic imaging methods that are used to detect this condition, as well as several treatment methods that could improve the health of individuals diagnosed with AS.

Integron frequency of Escherichia coli strains from patients with urinary tract infection in Southwest of Iran

Objective: To investigate the frequency of integrase genes intI1, intI2 and intI3 of Escherichia coli strains, and their association with resistance to routinely used antibiotics. Methods: A total of 120 Escherichia coli strains were collected from patients with urinary tract infection in Ahvaz, Southwest of Iran. Antibiotic susceptibility testing was performed. The presence of intI1, intI2, and intI3 genes was determined by polymerase chain reaction. Results: Antibiotic susceptibility testing disclosed the highest resistance rate to ampicillin (91.7%) followed by trimethoprim/sulfamethoxazole (65.8%), and ceftazidime (56.7%). The imipenem susceptibility rate was 91.7%. IntI1 and intI2 were identified in 74 (61.6%) and 8 (6.6%) of Escherichia coli strains, respectively, but intI3 was not found in any isolates. The presence of integrons was significantly associated with resistance to ampicillin, trimethoprim/sulfamethoxazole, ceftazidime, and ciprofloxacin antibiotics (P<0.05). Conclusions: The high resistant Escherichia coli isolates harboring class 1 integrons (intI1) were detected in patients with urinary tract infection in our region. Therefore, preventive strategies are necessary to restrict further dissemination of resistant strains.

Distribution and ecological aspects of sand flies(Diptera:Psychodidae) species in Northeastern Iran

Objective:To determine both the distribution and the ecological characteristics of sand flies in Golestan Province,northeast of Iran in 2016.Methods:In this study,34 villages were selected based on their geographical conditions.Sticky paper traps were used for collecting the sand flies.Sampling was carried out in each of villages from May to November.In each village,60 traps for indoors and 60 for outdoors were monthly installed.The species of all collected sand flies were determined using approved morphological keys.Pearson coefficient correlation was used to find the relationship between the number of collected Phlebotomus papatasi from different villages and incidence rate of zoonotic cutaneous leishmaniasis as well as the number of positive cases of the disease.The altitude of the studied villages was extracted from digital elevation model of the area using GIS and vegetation cover density index of the province was extracted from Modis satellite imagery and distribution map of sand flies drown up.Results:Overall,5 428 sand flies were collected and identified,belonging to 18 species.Phlebotomus wenyoni was reported for the first time from the area in this study.The frequency of sand flies in the villages located in northeast of the Golestan province(the plateau area,lower altitude,arid and semi-arid climates,and lower vegetation cover density),were more than other villages in this province.There was a significant correlation between the number of collected Phlebotomus papatasi and incidence rate of the zoonotic cutaneous leishmaniasis cases in different villages(r=0.837,P=0.019) as well as the number of positive cases of the disease(r=0.688,P<0.001).Conclusions:In the northeaster areas of Golestan Province which is known as the endemic foci of zoonotic cutaneous leishmaniasis,the abundance of sand flies were more and the conditions for their growth and development were more appropriate.

Epidemiology of upper gastrointestinal cancers in Iran:A Sub site analysis of 761 cases

AIM： To define the sub site distribution of upper gastrointestinal cancers in three provinces of Iran. METHODS： The study was carried out in three provinces in Iran： Ardabil, Golestan, and Tehran. In Arbabil and Golestan, the data was collected from the sole referral center for gastrointestinal cancers and the local cancer registry. For Tehran province, data from two major private hospitals were used. All gastric and esophageal cancer patients diagnosed during the period from September 2000 and April 2002 were included in the study.RESULTS： A total of 761 patients with upper gastrointestinal cancers were identified, 314 from Ardabil, 261 from Golestan, and 186 from Tehran. In Tehran, the relative rate of cancer increased from the upper esophagus to the distal stomach. In Golestan, the reverse pattern was observed. In Ardabil, the mid portion （distal esophagus and proximal stomach） was involved most frequently.CONCLUSION： There were considerable variations in the sub site of upper gastrointestinal cancers in the three provinces studied, We cannot provide any explanation for this variation, Further research aimed at explaining the discrepancies in sub site distribution of upper gastrointestinal cancers may help identify important risk factors.

Bone mineral density in Iranian patients: Effects of age, sex, and body mass index

Introduction: Osteoporosis is a multifactorial skeletal disease that is characterized by reduced bone mineral density (BMD). BMD values depend on several factors such as age, sex and age at menopause. The purpose of this study was to determine the prevalence and changes in bone mineral density in Iranian patients. Methods: Three hundred patients were selected through random sampling technique in 2009. BMD was assessed by Norland (Excell) technique at the lumbar and femoral neck. Weight and height were measured through standard methods. A thorough history was taken from each patient. The data was analyzed using SPSS software version 13.0. P-values less than 0.05 were considered statistically significant. Results: From among the 300 studied patients, 86.6% were female. their mean age was 52.7 years. Their average body mass index (BMI) was 28.14 kg/m2. Mean T-Score at lumbar spine and femoral neck was -1.07 ±1.19 and -1.75 ± 1.33 respectively. Mean BMD value at lumbar spine and femoral neck was 0.92 ± 0.19 and 0.77 ± 0.16 respectively. The prevalence of osteoporosis at lumbar spine and femoral neck was 33.7% and 16.7, respectively. There was a significant correlation between age, BMI and BMD values (P-Value Conclusion: This study shows that ageing and low BMI are risk factors associated with bone loss. it is recommended to measure BMD and implement prevention programs for high-risk people.

The Effect of Luteal-Phase Support with Triptrolin Administration on Implantation and Clinical Pregnancy Rate in Assisted Reproductive Technology

Background: Luteal phase support with GnRH agonist administration has been shown to be effective in improving the outcome of assisted reproductive technology. The goal of this study was to evaluate the effect of single dose Triptrolin (a GnRH agonist) on the probability of the clinical pregnancy rate following embryo transfer (ET) in assisted reproductive techniques (ART). Methods: In this double blinded randomized clinical trial, 340 infertile women who were candidates for intra-cytoplasmic sperm injection (ICSI) were randomly assigned to receive GnRH agonist (Triptrolin) in the luteal phase or placebo. In the intervention group, 0.1 mg Triptrolin was injected subcutaneously, while the control group received normal saline. The clinical pregnancy and implantation rate were compared between the two groups using chi-2 and t-test. P-values less than 0.05 were considered significant. The registration number of this clinical trial is IRCT 2014030916912N1. Results: Administration of 0.1 mg Triptrolin on day 6 after oocyte pick up showed no superiority over placebo in implantation (16.9% - 14%, P = 0.40) and clinical pregnancy rates (32% - 29%, P = 0.66), but the rate of clinical pregnancy was higher in women who were below 27 years of age and those with PCO. Conclusion: Administration of Triptrolin was not superior to placebo for luteal phase support.

National Approach to Premarital Diagnosis of Trait Thalassemia and Silent Carriers

Background: Major β-thalassemia occurs when impaired genes received by a neonate from the parents. In most of the parents, there are no apparent clinical manifestation and they just show some impairments in hematological indices. This study was designed to determine prevalence of minor and silent carries parents that have children suffering from major β-thalassemia, compare it with national protocol about prevention of thalassemia. Methods: A blood sample was taken from parents of all major thalassemic patients covered by TaleghaniHospitalin Gorgan (n = 195), CBC and Hemoglobin electrophoresis were done. Data were analyzed using SPSS software. Results: Amongst 196 parents one case have normal level of MCV, MCH, RBC, HbA, HbF and mentzer = 22.05 (0.51%) that diagnosed as alpha triplication/N by real time PCR, RFLP informative. The means of hematological indices were based on the national protocol. Conclusion: Present results showed that there are a few cases of thalassemia disorders with normal MCV, MCH, RBC, Mentzer index and Hb electrophoresis which could be missed in routine and pre-marital screening tests, resulted in a thalassemia child that it is possible in every screening test. Generally, indices were according to range of the national guideline.

New <i>Spa</i>Types among MRSA and MSSA Isolates in North of Iran

Staphylococcus aureus typing using gene encoding protein A (spa typing) seems to have a high potential discriminatory power for typing this bacterium. This study was designed based on spa typing method to compare the S. aureus types among healthy carrier vs patients, and MRSA vs MSSA isolates. Method: This study was carried out on 182 spa typeable S. aureus isolates, including 52 MRSA. DNA was extracted by phenol chloroform-isoamyl alcohol method and it was amplified by specific primer of polymorphic X region of spa. Spa types were determined by Ridom Staph Type software. The spa types distribution among MRSA vs MSSA and healthy carrier vs patients, isolates were statistically compared by X2 method and P < 0.05 was considered as significant. Result: The most common types of spa in our region were t037 (18.3%) and t937 (13.9%) from 50 spa types which were identified in this study. spa types in this study were isolated from various age groups but t660 spa types were only isolated from children. Distribution of all spa types among MRSA and MSSA isolates was 16 and 38 types, respectively which is significant. In this study we found seven new spa types (belong to twelve isolates) which are reported for the first time. In 5 out of the above 7 new types the 24 bp repeated sequences in spa gene X region were already recognized but their 24 bp arrangement is introduced in our present investigation. In the remaining 2 new types we found new 24 bp nucleotide sequences which are also introduced for the first time in our present study. Conclusion: The distribution of spa types in MSSA strains was significantly higher than MRSA isolates, but there are not any specific spa types for discrimination between MRSA and MSSA. The novelty of our study is the introducing 7 new spa types including 2 new 24 bp repeated sequences in the X region of spa gene.

Identification of Panton-Valentine leukocidin virulence gene in methicillin-resistant Staphylococcus aureus isolated from clinical specimens of burn patients in Zare Hospitals of Sari, Iran

Objective:To identify the pathogenic gene of Panton-Valentine leukocidin in methicillin-resistant Staphylococcus aureus strain isolated from clinical specimens of burn patients in Shaheed Zare Burn Hospital.Methods:A total of 104 samples of Staphylococcus were collected and 78 aureus samples were isolated from Zare Hospital patients from November 2016 to July 2017.All isolates were identified using a standard biochemical and laboratory methodology in accordance with CLSI principles,and disk agar diffusion antibiogram were performed to identify methicillin resistant colonies.Then the presence of the Panton-Valentine leukocidin gene was tested by PCR.Results:Of the methicillin-resistant Staphylococcus aureus samples,80%were negative for the Panton-Valentine leukocidin gene,and only 20%of the samples had Panton-Valentine leukocidin gene.Male and female patients showed no significant difference in the positivity rate of Panton-Valentine leukocidin gene(16.12%vs.33.33%)(P=0.25).Besides,there was no significant difference in bacterial resistance or susceptibility to antibiotics between samples with or without the Panton-Valentine leukocidin gene.Conclusions:In recent years,increased resistance has been a serious threat.The resistance or susceptibility of Staphylococcus aureus strains to different antibiotics is different in different geographical locations.

Healthcare utilization patterns and economic burden of animal bites:A cross-sectional study

Objective:To determine the healthcare utilization patterns and estimate the economic burden of animal bites in Golestan province,north part of Iran.Methods:This cross-sectional study was performed based on the data of 12181 animal-bite patients from Golestan province who were referred to the rabies prophylaxis centers between March 2019 and March 2020.The study was a societal perspective,and all patients were investigated by census method.The micro-costing method with a bottom-up approach as well as the human capital approach were used to estimate the economic burden.Results:In our study,the economic burden caused by animal bites was estimated at$1383639(275354672060 Rials).The largest share of costs was related to direct healthcare costs,direct non-healthcare costs,and indirect costs accouting for 91%,5%,and 4%,respectively.In addition,the average cost of a animal-bite patient was estimated at$113.5(22605260 Rials)(The average cost of a case in type 2 and 3 exposures was$45 and$412.8,respectively).The largest share of direct healthcare costs was related to immunoglobulin,vaccine,and personnel expenses accounting for 61.3%,19.8%,and 11.65%,respectively.Conclusions:Our study shows that animal bites in Golestan province,north of Iran impose a high economic burden on the communities,especially the healthcare system,which indicates the need to review management and control programs of animal bites and rabies based on animal-bite patterns of the area.

Advanced Primary Lymphoma of Oral Cavity: Report of a Case

Usually the oral manifestations of NHL are secondary to a more widespread involvement throughout the body, however, it can rarely present as a primary lesion in the oral cavity, having 0.1% - 0.2% prevalence. In this paper we report a case of highly proliferative oral non-Hodgkin lymphoma which presented with very mild symptoms, but had a sudden and significant progression in less than two weeks with involvement of all four quadrants of the oral cavity.