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Background and purpose: Cyclophosphamide (CP) is an alkylating anticancer drug and one of the most successful drugs with a wide range of clinical activities. This drug has toxic effects on most organs, especially kidney tissue. Piperine, as a flavonoid, has antioxidant, anti-inflammatory, and anti-apoptotic properties. The purpose of the present study is to investigate the antioxidant effect of piperine (PIP) on nephrotoxicity following cyclophosphamide (CP) by tissue, serum, and histopathological biochemical evaluation. Materials and methods: In this experimental study, 48 adult male BALB/c mice aged 6-8 weeks and weighing 30-35 grams were divided into 6 groups, the control group (C), the group receiving cyclophosphamide (CP) with a dose of 200mg/kg, the group receiving piperine (Pip) with a dose of 5mg/kg, the group receiving piperine (Pip) with a dose of 10mg/kg, the group receiving cyclophosphamide and piperine at a dose of 5mg/kg (CP+Pip) and the group receiving cyclophosphamide and piperine with A dose of 10mg/kg (CP+Pip) was used. CP was administered on the third day of the study. Piperine was prescribed for 7 days in the form of pre-treatment and post-treatment. On the eighth day of the study, histochemical (GSH and MDA), histopathology, and serum biochemical evaluations were performed. Then, the data were analyzed with GraphPad Prism software one-way ANOVA and Tukey's post hoc tests. Results: CP induced oxidative stress with a significant decrease in GSH level (P

Background: This study aimed to assess the serum activity of paraoxonase 1 (PON1) in patients with coronary artery disease (CAD) based on two genetic variants including the -108C/T variant in the promoter region and the rs3735590 variant in the binding site of miR-616 at the 3ʹ-UTR of the PON1 gene. Materials and Methods: A total of 140 subjects who exhibited clinical symptoms of CAD underwent diagnostic coronary angiography. The patients with CAD were further categorized into two groups: single-vessel disease (SVD) and multi-vessel disease (MVD). The study variants were genotyped using the restriction fragment length polymorphism (RFLP) technique after polymerase chain reaction amplification. Results: After adjusting for age, gender, body mass index, metformin, and statin usage, a significant association was observed between the -108C/T variant and PON1 activity (P < 0.001). In the sub-groups of both SVD and MVD, individuals with the TC+CC genotypes exhibited significantly higher PON1 activity compared to TT homozygotes (P = 0.001 for SVD and P = 0.01 for MVD). As for the rs3735590 variant, individuals with the A allele (GA+AA genotypes) had higher PON1 activity compared to those with the GG genotype in both the SVD and MVD groups, although the results did not reach statistical significance. Conclusions: Our study findings indicate a significant decrease in PON1 activity among patients with obstructive CAD. Notably, our results suggest that the -108C/T variant exerts a greater influence on PON1 activity compared to the rs3735590 variant. These findings highlight the crucial role of the -108C/T variant in modulating PON1 activity within the context of atherosclerosis.

Objective(s): Cyclophosphamide (CP) as an antineoplastic drug is widely used in cancer patients, and liver toxicity is one of its complications. Sinapic acid (SA) as a natural phenylpropanoid has anti-oxidant, anti-inflammatory, and anti-cancer properties.Materials and Methods: The purpose of the current study was to determine the protective effect of SA versus CP-induced liver toxicity. In this research, BALB/c mice were treated with SA (5 and 10 mg/kg) orally for one week, and CP (200 mg/kg) was injected on day 3 of the study. Oxidative stress markers, serum liver-specific enzymes, histopathological features, caspase-3, and nuclear factor kappa-B cells were then checked.Results: CP induced hepatotoxicity in mice and showed structural changes in liver tissue. CP significantly increased liver enzymes and lipid peroxidation, and decreased glutathione. The immunoreactivity of caspase-3 and nuclear factor kappa-B cells was significantly increased. Administration of SA significantly maintained histochemical parameters and liver function enzymes in mice treated with CP. Immunohistochemical examination showed SA reduced apoptosis and inflammation. Conclusion: The data confirmed that SA with anti-apoptotic, anti-oxidative, and anti-inflammatory activities was able to preserve CP-induced liver injury in mice.

Abstract COVID-19 currently is the main cause of the severe acute respiratory disease and fatal outcomes in human beings worldwide. Several genes are used as targets for the detection of SARS-CoV-2, including the RDRP, N, and E genes. The present study aimed to determine the RDRP, N, and E genes expressions of SARS-CoV- 2 in clinical samples. For this purpose, 100 SARS-CoV-2 positive samples were collected from diagnostic laboratories of Mazandaran province, Iran. After RNA extraction, the real-time reverse transcription PCR (real-time RT-PCR) assay was performed for differential gene expressions’ analysis of N, E, and RDRP. The threshold cycle (Ct) values for N, RDRP, and E targets of 100 clinical samples for identifying SARS-CoV-2 were then evaluated using quantitative real-time PCR (qRT-PCR). This result suggests N gene as a potential target for the detection of the SARS-CoV‐2, since it was observed to be highly expressed in the nasopharyngeal or oropharynges of COVID-19 patients (P

Background: Human epidermal growth factor receptor 2 (HER2) is over-expressed in breast, ovarian, gastric, and prostate cancers and is used as a tumor marker in the diagnosis of cancer. Monoclonal antibodies have been used as a diagnostic and therapeutic tool against HER2. Because of the difficulties associated with the stability and complexity of the construct and the high cost of antibody production, we aimed to investigate, cloning, and expression of HER2- binding DARPins genes to identify, HER2-positive tumor markers, we aimed to investigate. Materials and Methods: After synthesis, the DARPins peptide gene was cloned into the M13 vector and sub-cloned into the TOP10 pet28b bacterial vector. After culturing the bacteria on an agarose plate containing antibiotics, the transfected bacteria expressing the DARPins gene were selected. To ensure gene cloning, we used enzymatic digestion and recombinant plasmid delivery for sequencing. Isopropyl β-d-1-thiogalactopyranosideIPTG was used for the induction of recombinant protein expression and the SDS-PAGE method and Western blot for expression confirmation. Results: The polymerase chain reaction (PCR) amplification product of DARPins was analyzed using agarose gel electrophoresis. Plasmid was purified from the positive clone by PCR cloning, sequenced and gene cloning was confirmed. After culturing from competent cells, protein expression was obtained from positive colonies. SDS- PAGE results showed the effect of different conditions including temperature, IPTG concentration, and time on the pET-DARPins expression. Conclusion: We were succeeded to express a new codon-optimized DARPins gene in Escherichia coli and HEK293t system.

Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been a major concern since it first emerged. Prevention of Coronavirus 2019 disease (COVID-19) and slowing the epidemic and prevalence of the disease are the main goals of health institutions all over the world. it is very difficult to control the disease and predict its prevalence due to the continuous changes in the form of single nucleotide polymorphism (SNP) and mutations in this virus. In fact, some changes and mutations in Corona 2019 virus directly affect the pathogenicity and its transmission. The most important mutations that occur in the spike or RBD part of the SARS-CoV-2 virus, change the function of the virus, its severity of pathogenesis, and creates new variants. Mutations in these variants change the ability of the virus in binding to human cells, the rate of transmission, and make it easier to escape the immune system which plays a role in the effectiveness or ineffectiveness of vaccines. This study reviews eight major mutations in the spike or RBD region, their presence in different variants of Corona 2019 virus, and their relationship with response rate in infected people. Search keywords included COVID-19, mutation, variant, coronavirus, and respiratory infection in Google Scholar, PubMed, Springer, ScienceDirect, and Scopus databases. The main variations made from SARS-CoV-2 are Alfa (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) that cause the infection to spread faster and the adequacy of vaccination on these variations have not been conclusively analyzed at this point.

Purpose: Emerging evidence implies that electromagnetic fields (EMFs) can negatively affect angiogenesis. In this regard, the effects of extremely low frequency pulsed electromagnetic field (ELF–PEMF) exposure on the relative expression level of angiogenic factors involved in the pathogenesis of ocular disorders were evaluated in human retinal pigment epithelial (hRPE) cells in order to investigate a noninvasive therapeutic method for patients with several ocular diseases associated with neovascularization. Methods: After separating hRPE cells from globes, hRPE cells were exposed to 15 mT of ELF–PEMF (120 Hz) at 5, 10, and 15 min for seven days. Cell proliferation and apoptosis of treated cells were evaluated via ELISA assay. Moreover, relative expression changes of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 were performed using real-time RT-PCR. Results: ELF–PEMF exposure had no significant effects on the apoptosis and proliferation rate of hRPE cells. Expression level of HIF-1α, CTGF, VEGFA, MMP-2, cathepsin D, and E2F3 was downregulated following 5 min of ELF–PEMF exposure. Conclusion: As ELF–PEMF showed inhibitory effects on the expression of angiogenic genes in hRPE cells with no cytotoxic or proliferative side effects, it can be introduced as a useful procedure for managing angiogenesis induced by retinal pathogenesis, although more studies with adequate follow-up in animal models are needed.

Background: Sodium arsenate (Na 3As0 4, Sodium As) is an important toxic substance that leads to nephrotoxicity. Due to having bioactive molecules, such as polyphenols and tyrosol, olive oil plays a significant role in scavenging free radicals. This study aimed to investigate the effects of olive oil and tyrosol on As-induced nephrotoxicity. Methods: In our study, 42 adult male BALB/c mice were randomly divided into six groups: control (normal saline), olive oil (0.4 ml/d, gavage), tyrosol (5 mg/kg/d), Sodium As (15 mg/kg), olive oil + Sodium As, and tyrosol + Sodium As (olive oil and tyrosol received one hour before Sodium As). Drugs were administreted once daily for 30 consecutive days. On the 31st day of the study, oxidative stress parameters in kidney tissue, FRAP in plasma, renal function parameters in serum, and histopathological assays were performed. Results: Sodium As-induced renal damage as characterized by a significant increase of creatinine and BUN (P < 0.001) and histopathological changes. Also, Sodium As markedly altered oxidative stress biomarkers such as a significant increase in MDA (P < 0.001) and significantly decreased in FRAP and GSH (P < 0.01). Olive oil and tyrosol administration significantly improved the renal antioxidant defense system and decreased MDA concentration, markedly preserving the tissue structure and functional markers of kidney. However, these effects were more effective for tyrosol than olive oil. Conclusions: Our results suggest that olive oil and tyrosol can be used as a protective agent in preventing Sodium As-induced nephrotoxicity due to antioxidant property.

Abstract Aims Cisplatin (CP), as an effective alkylating agent, is widely used in cancer treatment, while hepatotoxicity is one of its side effects. Gliclazide (GLZ), as an oral hypoglycemic drug, has antioxidant and anti‐inflammatory properties. This study was designed to investigate the protective effect of GLZ against CP‐induced hepatotoxicity in mice. Methods In this experimental study, 64 adult male mice randomly were allocated into eight groups (8 mice/group). Control, GLZ (5, 10, and 25 mg/kg, orally), CP (10 mg/kg, single dose, intraperitoneally), and CP+GLZ (in three doses). GLZ was administrated for 10 consecutive days. CP was injected on the 7th day of the study. At the end of the experiment, hepatotoxicity was evaluated by serum and tissue biochemical, histopathological, and immunohistochemical assessments. Results The data were revealed that CP increased oxidative stress (increased MDA and reduced GSH), liver damage enzymes (ALT, AST, and ALP), and immunoreactivity of caspase‐3 in liver tissue of CP‐injected mice. Also, CP induced histopathological changes such as eosinophilic of hepatocytes, dilatation of sinusoids, congestion, and proliferation of Kupffer cells. GLZ administration significantly ameliorated serum functional enzyme and hepatic oxidative stress markers in CP‐injected mice. In addition, the histological and immunohistochemical alterations were ameliorated in GLZ‐treated mice. Of the three doses, 10 and 25 mg/kg were more effective. Conclusions In conclusion, GLZ with its antioxidant, anti‐inflammatory, and anti‐apoptotic activities, can be suggested as a promising drug in the treatment of CP‐induced hepatotoxicity.

Objective: Type 2 diabetes mellitus (T2DM) is a multifactorial disorder with various disturbances in biochemical processes such as antioxidant status and lipid peroxidation. The aim of present study was evaluation of the oxidative stress markers in saliva of T2DM patients. Materials and Methods: In this study, 80 (40 T2DM and 40 control) individuals were assessed. The salivary total antioxidants capacity and lipid peroxidation were determined by the ferric reducing antioxidant power (FRAP) method and Thiobarbituric acid reactant substances (TBARS) assay, respectively. Results: Total salivary antioxidants value was significantly lower in T2DM patients compared with healthy controls (P -value: 0.01). A significant increase in lipid peroxidation was seen in T2DM (P-value: 0.0001). Conclusion: The findings of the present study suggest that diabetic patients confront a disturbed state of antioxidant defense, especially the reduction in total antioxidant capacity of body.

Abstract CD22 marker is a highly internalizing antigen which is located on the surface of B-cells and is being used as a promising target for treatment of B cell malignancies. Monoclonal antibodies targeting CD22 have been introduced and some are currently under investigation in clinical trials. Building on the success of antibody drug conjugates, we developed a fusion protein consisting of a novel anti-CD22 scFv and apoptin and tested binding and therapeutic effects in lymphoma cells. The recombinant protein was expressed in E. coli and successfully purified and refolded. In vitro binding analysis by immunofluorescence and flow cytometry demonstrated that the recombinant protein specifically binds to CD22 positive Raji cells but not to CD22 negative Jurkat cells. The cytotoxic properties of scFv–apoptin were assessed by an MTT assay and Annexin V/PI flow cytometry analysis and showed that the recombinant protein induced apoptosis preferentially in Raji cells with no detectable effects in Jurkat cells. Our findings indicated that the recombinant anti-CD22 scFv–apoptin fusion protein could successfully cross the cell membrane and induce apoptosis with high specificity, make it as a promising molecule for immunotherapy of B-cell malignancies.

Background: Free radicals production by toxicity of arsenic (Ar) is most important in the nephrotoxicity. There is accumulating evidence that zinc (Zn), has anti-oxidant properties. Objectives: The aim of present study was to evaluate protective and ameliorative effects of Zn against Ar-induced nephrotoxicity in rat pups during gestation and lactation. Materials and Methods: Twenty-four adult pregnant wistar rats were randomly divided into four groups (n = 6). Group one was given vehicle only. Group two received Zn (ZnSO4) at 20 mg/kg/d. Group three received Ar at 5 mg/kg/d as sodium meta-arsenite. Group four received Ar + Zn at the same dose that mentioned in groups of two and three. At the end of the study, 24 hours after the last treatment, samples were killed with overdose of sodium pentobarbital and kidneys were harvested for measuring malondialdehyde (MDA), glutathione (GSH) and histopathological assessment. Results: The MDA level in kidney was increased in the Ar group, which was decreased after Zn administration in the Ar + Zn group. The GSH level in kidney was decreased in the Ar group, which were increased after Zn administration in the Ar + Zn group. Also, the histopathological changes which were detected in the Ar group attenuated after Zn consumption. Conclusions: Our findings suggested that administration of Zn during gestation and lactation could have protective and prevent effect in Ar-induced oxidative stress in kidney tissue.

Introduction: Acute Coronary Syndrome (ACS) includes a spectrum of disorders ranging from unstable angina to myocardial infarction. Since, ACS is an important cause of mortality in the world, early diagnosis of the disease is very important. Ischaemia Modified Albumin (IMA) is an ischaemia biomarker that has been approved by the US Food and Drug administration and has clinical application. Although, many studies have been done on IMA as a biomarker in ACS patients, role of IMA for differentiating patients with unstable angina, Non ST-Segment Elevation Myocardial Infarction (NSTEMI) and ST-Segment Elevation Myocardial Infarction (STEMI) requires further study. Aim: To assess the diagnostic role of IMA in ACS patients and evaluate correlation between IMA and necrotic biomarkers such as cardiac Troponin I (cTnI) and Creatine kinase-myoglobin binding (CKmb) in ACS patients. Materials and Methods: The study included 75 subjects with ACS, who were divided into three groups of 25 patients each: Unstable angina, NSTEMI and Myocardial Infarction (MI) and 25 healthy people as control. They were enrolled into the study from the Fatemeh Zahra Heart Center, Sari, Iran, between November 2015 and October 2016. IMA was measured by the CobaltAlbumin Binding (CAB) assay, cTnI was measured by rapid immunoassay and CKmb was estimated utilising colorometric enzyme method by commercial kits. The correlation between IMA and necrotic biomarkers was determined using a Pearson correlation analysis. Receiver Operator Characteristic (ROC) curve was used to assess role of IMA in diagnosis of ACS. Results: IMA levels in unstable angina patients were significantly higher than NSTEMI and MI (p0.5, r=0.25). The area under the ROC curve of IMA for ACS patients was 0.783. The sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) of IMA was 74.7%, 72%, 88.9% and 48.6% respectively. Conclusion: IMA is a useful biomarker in diagnosis of ACS especially unstable angina patients and there is no significant correlation between IMA and necrotic biomarkers (cTnI and CKmb) in ACS patients.

Background: The role of attenuation in antioxidant capacity or expansion of pro-oxidant/oxidant is well known for the development of stress oxidative. The aim of this study was to evaluate the plasma antioxidant capacity along with uric acid in patients with diabetic nephropathy (DN+) and without diabetic nephropathy (DN-). Materials and Methods: The research population included 88 patients with DN, 66 patients without DN and 54 healthy people who were matched for age, gender, and body mass index (BMI). In all groups, total antioxidant capacity of plasma by the ferric reducing antioxidant power (FRAP) assay and serum uric acid by commercial kit, respectively. Results: The mean age of patients in DN+, DN- and control groups were 59.3± 9.4, 60 ±11.2, and 54.6±6.9 years, respectively. Plasma antioxidant capacity was higher in patients with DN+, (1589±330&mu mol/l Fe2+) and DN- (1344± 347 &mu mol/l Fe2+) than that in healthy controls (1187±271 &mu mol/l Fe2+ ) (P

Background: The female breast is subjected to a lifetime of hormonal controls, whose effect is evident at the time of menarche and during the menstrual cycle, pregnancy and lactation. Studies have reported multiple risk factors for breast cancer, some of which are a reflection of hormonally mediated events. The steroid receptors are also served as prognostic factors for evaluating status of malignant tumor of the breast. Estrogen receptor (ER) and progesterone receptor (PgR) formation are influenced by Estrogen and progesterone concentration. The aim of this study was to clarify the hormonal milieu of the breast cancer such as Estradiol (E2), Progesterone (Pg), Prolactin (PRL) and their correlation with prognostic factors like ER, PgR. Materials and Methods: In this study we examined fourthy four samples removed from patients with primary breast cancer by radical mastectomy. The specimens include thirty six malignant and eight benign breast tissues. Blood samples were also obtained before surgery. steroid receptors was assayed by the method of single-point dextrane-coated charcoal (DCC), hormones by radioimmunoassay. Results: The results demonstrated that serum prolactin was higher in patients with benign and malignant tumors than that of normal (progesterone1.5 ng/ml and those of

Introduction: Diabetic Nephropathy (DN), a serious complication of Type 2 Diabetic Mellitus (T2DM), is progressive and susceptibility to DN varies among T2DM patients. ApoA51131T>C polymorphism revealed that is strongly associated with triglyceride levels and proposed as a predisposing factor for DN. Aim: The purpose of this study was to investigate the association -1131T>C ApoA5 gene polymorphism with serum lipids levels in Type 2 diabetic (DM) patients with or without DN in north of Iran (Mazandaran province). Materials and Methods: This study comprised patients with established T2DM (n=161) and controls (n=58). Genotyping of APOA5 -1131T>C polymorphisms was performed by PCR– RFLP. Diabetic patients were divided into two groups: with nephropathy (DN+, n = 90) and without nephropathy (DN-, n = 71). Lipids and lipoproteins were assessed by enzymatic methods. Results: The genotype frequencies were 63.8 % TT, 31 % TC, 5.2 % CC in controls, 33.8% TT, 52.1 % TC, 14.1 % CC in DN- and 44.4 % TT, 36.7 % TC, 18.9 % CC in DN+ patients. The TC genotype and the CC genotype were overexpressed among DN+ and DN-population in comparison to the control group. The highest and the lowest TG levels in both diabetic patients and controls belonged to CC+TC and TT genotypes, respectively. Furthermore in both patients TG increased with this order: TT< TCC polymorphisms influence lipid levels in type 2 diabetic patients.

Introduction: Uric acid has antioxidant activity and it is expected to protect against coronary artery disease (CAD). Contradictory, it is a component of metabolic syndrome and so a risk factor for CAD. The associations of plasma total antioxidant capacity (TAOC) and uric acid (UA) as well as other risk factors were investigated relative to the occurrence and severity of CAD. Materials and Methods: The study population consisted of 148 males and 152 females aged 35-76 years who were classified as CAD cases and controls according to the results of coronary angiography. The severity of CAD was scored on the basis of the number and the extent of lesions at coronary arteries. The concentrations of UA and TAOC were measured by using of FRAP and enzymatic uricase methods. Results: The prevalence of hypertension, cigarette smoking and diabetes mellitus was more frequent in CAD cases than controls. Patients with CAD when compared with the controls had increased levels of glucose, triglycerides, creatinine, UA, TAOC and decreased levels of HDL- cholesterol. Serum UA was high positive correlate of serum total and LDL-cholesterol, triglyceride, creatinine, BUN, bilirubin, TAOC and negative correlate of glucose and HDL-C. TAOC and its major determinant UA but not bilirubin and albumin are significantly associated with the prevalence and severity of CAD. In multivariate analysis and in the absence of hypertension, UA but not TAOC would remain and be associated with CAD by the OR of 1.57 (1.07- 2.29), p=0.02. If the results adjusted for all major risk factors including hypertension, neither TAOC nor UA would remain in the regression equation. Conclusion: The results suggest that TAOC and UA but not bilirubin and albumin are associated with CAD significantly. But, the correlation is not independent and is attributed to the metabolic syndrome. The measurement of UA and TAOC will not improve the prognostic power beyond the classical risk factors.

Background: Sodium arsenate (As), a toxic substance with induced oxidative stress, lead to hepatotoxicity. Olive oil (OO) with antioxidant property has protective effect on toxicity. The aim of this study was to investigate protective effect of OO on sodium As-induced hepatotoxicity in mice. Subjects and Methods: In this experimental study, 32 adult male BALB/c mice were divided randomly into four groups: control group (received only normal saline, the same volume as other groups), OO (0.4 mL/day, gavage), sodium As (15 mg/kg, gavage), and OO + sodium As (received OO 1 h before sodium As). Drugs were given for 30 consecutive days. After the last receipt of the drugs, oxidative stress parameters [malondialdehyde (MDA), glutathione (GSH)] in tissue, liver function parameters [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)] in serum, ferric reducing ability of plasma (FRAP) in plasma, and histopathological assays were performed. Results: Sodium As induced hepatic injury as indicated by significant increase in AST, ALT, ALP, and LDH in serum and pathologic evidences. It also induces hepatic oxidative stress biomarkers as indicated by significant increase in levels of MDA and significant decrease in FRAP and GSH concentration. OO administration significantly improved oxidative stress parameters, histopathological changes, and enzymatic markers of liver injury. Conclusions: It was concluded that antioxidant activity of OO has hepatoprotective effect on As-induced hepatic injury.