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Tyrosinase is an essential enzyme in melanin production, which plays an important role in the browning of plants and vegetables and skin diseases in humans. Therefore, the design and synthesis of tyrosinase inhibitors are important in the food industry and in treating melanin-related skin diseases. In this study, the tyrosinase inhibitory activity and the antioxidant capacity of a series of 3-hydroxypyridin-4-one derivatives that have been synthesized in the Department of Medicinal Chemistry at the Faculty of Pharmacy, Shiraz University of Medical Sciences, were assessed. The antioxidant activities were evaluated using the 1,1-diphenyl-2-picrylhydrazine (DPPH) radical scavenging method. The biological results indicated that these derivatives exhibit mild anti-tyrosinase and antioxidant properties. Docking studies were also conducted, and the results showed that the compounds have suitable binding free energy and interactions with the active site of the tyrosinase enzyme, which were not consistent with the biological results. Finally, the investigation of the pharmacokinetic characteristics and drug-likeness of the derivatives showed that they have the potential for oral bioavailability.

Abstract Leukemia inhibitory factor (LIF) is involved in the progression of different cancers. In this study, we investigated the effect of anti-LIF antibodies on immune-related gene expression in the Balb/c mouse model of breast cancer. To immunize mice against LIF, recombinant LIF with Freund adjuvant was injected into the test group, whereas the control group received phosphate-buffered saline with adjuvant. Tumor induction (4T1 cell line) was performed by increasing the antibody titer. The expression of immune-related genes was evaluated by real-time PCR. The anti-LIF titer was significantly increased in the immunized group. The expression of genes related to the differentiation of T helper (Th)-1, Th-2, and Th-17 cells was significantly higher in the immunized group than in the control group. In addition, anti-LIF did not have a significant effect on the expression of genes related to the differentiation of regulatory T cells, and immune checkpoint-associated genes. Additionally, the test group had higher survival and lower tumor development rates. The results demonstrated that the anti-LIF antibody may potentially play a role in the differentiation of immune cells or immune responses. However, further studies utilizing advanced techniques are necessary to validate its function.

Objective: To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide. Methods: Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage (control), acrylamide 20 mg/kg body weight, acrylamide plus probiotic microorganisms (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus bulgaricus, Lactobacillus rhamnosus, Bifidobacterium breve, Bifidobacterium infantis, Streptococcus thermophilus and fructooligosaccharides, all mixed in sachets) 20 or 200 mg/kg body weight, respectively. After 30 days, the testis, prostate, seminal vesicle and cerebellum were removed, fixed and stained with hematoxylin-eosin (H & E). The Johnsen score was used to classify spermatogenesis. Cavalieri's principle method was used to evaluate the total volume (in mm3) of the testes. The number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting techniques. Stereological analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell number. Results: The testis weight decreased significantly in the acrylamide- treated group compared to the other groups (P

Abstract Based on unselectively, several side effects and drug resistance of available anticancer agents, the development and research for novel anticancer agents is necessary. In this study, a new series of quinazoline-4(3H)-one derivatives having a thiol group at position 2 of the quinazoline ring (8a-8 h) were designed and synthesized as potential anticancer agents. The Chemical structures of all compounds were characterized by 1H-NMR, 13C-NMR, and Mass spectroscopy. The antiproliferative activity of all derivatives were determined against two cancer cell lines (MCF-7 and SW480) and one normal cell lines (MRC-5) by the MTT method. Cisplatin, Erlotinib and Doxorubicin were used as positive controls. The results of in vitro screening showed that 8a with an aliphatic linker to SH group was the most potent compound with IC50 values of 15.85 ± 3.32 and 17.85 ± 0.92 µM against MCF-7 and SW480 cell lines, respectively. 8a indicated significantly better potency compared to Erlotinib in the MCF-7 cell line. The cytotoxic results obtained from testing compound 8a on the normal cell line, revealing an IC50 value of 84.20 ± 1.72 µM, provide compelling evidence of its selectivity in distinguishing between tumorigenic and non-tumorigenic cell lines. Structure–activity relationship indicated that the variation in the anticancer activities of quinazoline-4(3H)-one derivatives was affected by different substitutions on the SH position. Molecular docking and MD simulation were carried out for consideration of the binding affinity of compounds against EGFR and EGFR-mutated. The binding energy of compounds 8a and 8c were calculated at -6.7 and − 5.3 kcal.mol− 1, respectively. Compounds 8a and 8c were found to establish hydrogen bonds and some other important interactions with key residue. The DFT analysis was also performed at the B3LYP/6–31 + G(d, p) level for compounds 8a, 8c and Erlotinib. Compound 8a was thermodynamically more stable than 8c. Also, the calculated theoretical and experimental data for the IR spectrum were in agreement. The obtained results delineated that the 8a can be considered an appropriate pharmacophore to develop as an anti-proliferative agent.

The Recent development of 2-DOF electrical machines leads to increasing need for 2-DOF position sensors. Using a planar sensor instead of two linear ones decreases the complexity, and cost of the employed drive. Therefore, in this paper a new slotless configuration is proposed for the planar resolver, that simplifies the manufacturing of the sensor. Then, the optimal combination of the stator/mover number of coils is determined based on the proposed analytical model. Finally, to reduce the number of integrated parts of the proposed resolver, a new configuration with skewed coils is proposed. The success of the developed model and the presented configuration is validated using three-dimensional finite element analysis.

Abstract Background: Endometriosis is a chronic estrogen-related inflammatory disorder that is known by proliferating endometrial cells in a place outside the uterus. The high presence of immune cells in the peritoneal fluid of women with endometriosis confirms the involvement of the immune system in the pathogenesis of the disease. Mucosal-associated invariant T (MAIT) cells play an undeniable impact on mucosal immunity by the production of interleukin-17, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha. The function of the cells in the pathogenesis of endometriosis is less investigated. Objective: This study aims to investigate the infiltration of MAIT cells by using the determination levels of V α 7.2-J α 33 gene expression in eutopic and ectopic tissue of endometriosis lesions. Materials and Methods: In this case-control study, the tested samples include 20 eutopic and 20 ectopic tissues of women with endometriosis and 20 uterine endometrial tissues of women in the control group. Expressions of the V α 7.2-J α 33 tumor necrosis factor-alpha, interleukin-17A, and IFN-γ genes were analyzed by quantitative reverse transcriptase-polymerase chain reaction. Results: According to the results, V α 7.2-J α 33 gene expression did not show substantial elevation in the uterine and eutopic endometrial tissues compared to internal gene control as well as in ectopic tissues. Correlation analysis approved a positive relationship between V α 7.2-J α 33 expression genes and IFN-γ levels in ectopic tissues. Conclusion: Considering the low-expression specific gene of MAIT cells in ectopic tissue, it can be concluded that these cells are present in the endometriotic environment to a certain extent, and there is a possibility of their role in the progression of endometriosis by secreting IFN- γ .Key words: Endometriosis, MAIT, IFN- γ , TNF- α , TCR V alpha 7.2-J alpha33, IL-17.

Abstract DPP4 inhibitors can control glucose homeostasis by increasing the level of GLP-1 incretins hormone due to dipeptidase mimicking. Despite the potent effects of DPP4 inhibitors, these compounds cause unwanted toxicity attributable to their effect on other enzymes. As a result, it seems essential to find novel and DPP4 selective compounds. In this study, we introduce a potent and selective DPP4 inhibitor via structure-based virtual screening, molecular docking, molecular dynamics simulation, MM/PBSA calculations, DFT analysis, and ADMET profile. The screened compounds based on similarity with FDA-approved DPP4 inhibitors were docked towards the DPP4 enzyme. The compound with the highest docking score, ZINC000003015356, was selected. For further considerations, molecular docking studies were performed on selected ligands and FDA-approved drugs for DPP8 and DPP9 enzymes. Molecular dynamics simulation was run during 200 ns and the analysis of RMSD, RMSF, Rg, PCA, and hydrogen bonding were performed. The MD outputs showed stability of the ligand–protein complex compared to available drugs in the market. The total free binding energy obtained for the proposed DPP4 inhibitor was more negative than its co-crystal ligand (N7F). ZINC000003015356 confirmed the role of the five Lipinski rule and also, have low toxicity parameter according to properties. Finally, DFT calculations indicated that this compound is sufficiently soft.

Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients.Keywords: Synthesis, Deferiprone, Maltol, Methylamine, Iron chelating agent.

In the present study, ten new substituted 3-hydroxypyridine-4-one derivatives were synthesized in a four-step method, and their chemical structures were confirmed using various spectroscopic techniques. Subsequently, the inhibitory activities of these derivatives against tyrosinase enzyme and their antioxidant activities were evaluated. Amongest the synthesized compounds, 6b bearing a 4-OH-3-OCH3 substitution was found to be a promising tyrosinase inhibitor with an IC50 value of 25.82 μM, which is comparable to the activity of kojic acid as control drug. Kinetic study indicated that compound 6b is a competitive inhibitor of tyrosinase enzyme, which was confirmed by molecular docking results. The molecular docking study and MD simulation showed that compound 6b was properly placed within the tyrosinase binding pocket and interacted with key residues, which is consistent with its biological activity. The DFT analysis demonstrated that compound 6b is kinetically more stable than the other compounds. In addition, compounds 6a and 6b exhibited the best antioxidant activities. The findings indicate that compound 6b could be a promising lead for further studies.

Abstract The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil–azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated. The compounds were synthesized by using 3-methyl-6-chlorouracil as the starting material. Cytotoxicity was determined using MTT assay in the breast carcinoma cell line (MCF-7) and Hepatocellular carcinoma cell line (HEPG-2). These derivatives demonstrated powerful inhibitory activity against breast and hepatocellular carcinoma cell lines in comparison to Cisplatin as positive control. Among these compounds, 4j displayed the best selectivity profile and good activity with IC50 values of 16.18 ± 1.02 and 7.56 ± 5.28 µM against MCF-7 and HEPG-2 cell lines respectively. Structure–activity relationships revealed that the variation in the cytotoxic potency of the synthesized compounds was affected by various substitutions of benzyl moiety. The docking output showed that 4j bind well in the active site of EGFR and formed a stable complex with the EGFR protein. DFT was used to investigate the reactivity descriptors of 4a and 4j. The outputs demonstrated that these uracil–azole hybrids can be considered as potential cytotoxic agents.

A series of ethyl 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[4,3-b]pyran-3-carboxylate derivatives (4a-j) bearing different substitutions on the C4-phenyl ring was synthesized. The anti-proliferative activity of all the synthesized compounds was assessed against two human cancer-cell lines, including SW-480 and MCF-7, by using MTT method. Derivatives 4g, 4i, and 4j, possessing 4-NO2, 4-Cl, and 3,4,5-(OCH3)3 substitutions, were found to be the most potent compounds against both cell lines. The obtained IC50 values for 4g, 4i, and 4j were 34.6, 35.9, and 38.6 μM against SW-480 cells and 42.6, 34.2, and 26.6 μM against MCF-7 cells, respectively. Evaluation of the free radical scavenging potential of the compounds against DPPH radicals showed the highest result for compound 4j with an EC50 value of 580 μM. Molecular docking studies revealed the compounds were well accommodated within the binding site of cyclin-dependent kinase-2 (CDK2) with binding energies comparable to those of DTQ (the co-crystallized inhibitor) and BMS-265246 (a well-known CDK2 inhibitor). Molecular dynamics simulation studies confirmed the interactions and stability of the 4g-CDK2 complex. All derivatives, except 4g, were predicted to comply with the drug-likeness rules. Compound 4j may be proposed as an anti-cancer lead candidate for further studies due to the promising findings from in-silico pharmacokinetic studies, such as high GI absorption, not being a P-gp substrate, and being a P-gp inhibitor. Density functional theory (DFT) analysis was performed at the B3LYP/6–311++G (d,p) level of theory to examine the reactivity or stability descriptors of 4d, 4g, 4i, and 4j derivatives. The highest value of energy gap between HOMO and LUMO and thermochemical parameters were obtained for 4i and 4j.

Abstract Background Breast cancer is one of the most common cancers. Leukemia inhibitory factor (LIF) is considered as one of the effective factors in the growth of breast cancer, and anti-leukemia inhibitory factor antibody is considered as one of the treatment options for this type of cancer. Methods Mice models of breast cancer were made with 4T1 cell line and were randomly divided into four groups. The first group included the mice that received anti-LIF (Anti LIF group). The mice in the second group received anti-LIF and doxorubicin (Anti LIF & DOX). The mice in the third group received only doxorubicin (DOX). Finally, the mice in the fourth group did not receive any intervention. 22 days after tumor induction, some of the mice were killed, and their tumor tissues, lymph nodes, and spleens were separated for evaluating P53, Caspase-3, TIM-3, LAG-3, CTLA-4, and PD-1 genes expression. The percentage of regulatory T cells and level of interferon gamma (IFN-γ) and transforming growth factor-beta (TGF-β) were evaluated. The rest of the mice were kept to check the tumor size and their survival rate. Results The proposed intervention did not have any significant effect on the tumor growth and the survival rate. However, the expression of P53 gene and Caspase-3 in the tumor tissue of the Anti LIF group had a significant enhancement. In tumor tissues and lymph nodes, the expression of T-bet, PD-1, TIM-3, and LAG-3 genes in the Anti LIF group showed a significant increase. There was no significant difference between groups in the percentage of regulatory T cells and level of IFN-γ and TGF-β. Conclusions The proposed interventions were able to have a direct effect on tumors, but no significant effect was observed on the immune system.

Abstract Background Tyrosine kinase inhibitors (TKIs) are prescribed as a targeted therapy to treat chronic myeloid leukemia patients. A challenge in clinical practice is that despite excellent efficacy and improved clinical response levels acquired by imatinib, a number of patients receive TKI therapy but have a poor primary response, develop a drug resistance, or relapse after initial success. This inter-individual difference into response has increased the concern in investigating the pharmacogenetics of cancer drugs. This review discusses the influence of various factors, such as BCR-ABL point mutation, efflux and influx transporters, and others, on targeted drug response in CML. Additionally, we focus on how patients can overcome these issues.

Background: Despite of long-lasting efforts, in more than 50% of cases, the etiology of recurrent spontaneous abortion (RSA) remains unknown. Leukemia inhibitory factor (LIF) has an essential role in the reproductive process, such as modulating inflammatory responses. This study aimed to evaluate the relationship between the LIF gene expression as well as serum levels of inflammatory cytokines and occurrence of RSA in infertile women with a history of RSA.Materials and Methods: In this case-control study, the relative gene expression levels of LIF, concentrations of tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-17 were measured in peripheral blood and serum of women with a history of RSA (N=40) compared with non-pregnant and fertile women as the control group (N=40) using quantitative real-time polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively.Results: The mean age of patients and controls was 30.1 ± 4.28 and 30.03 ± 4.23, respectively. Patients had a history of at least 2 and at most 6 abortions. The mRNA levels of LIF were significantly lower in the women with RSA in comparison with the healthy participant (P=0.003). Regarding cytokine levels, no significant difference was seen between the two groups (P≥0.05). There was no correlation - between the LIF mRNA levels and TNF-α and IL-17 serum concentrations. The U-Mann-Whitney test and the Pearson correlation coefficient were applied to comparison variables between groups as well as a correlation between LIF mRNA and cytokine levels in serum.Conclusion: Despite a significant reduction in the LIF gene mRNA level in patients with RSA, it was not associated with increases in inflammatory cytokines. Dysfunction in the production of LIF protein may be involved in the onset of RSA disorder.

In this paper, an analytical model based on the Magnetic Equivalent Circuit (MEC) method is developed for a planar wound mover two-degree of freedom (2-DOF) resolver. Planar resolvers enable mass, volume, and complexity reductions for position control of 2-DOF linear actuators. However, similar to any other linear electromagnetic sensors, the performance of the planar resolvers is negatively affected by the limited dimensions of the mover’s ferromagnetic core. Thus, it is necessary to develop an appropriate compensation method. On the other hand, the 3-D geometry of the sensor necessitates extremely time consuming 3-D time-stepping analysis. Therefore, a fast yet accurate analytical model is critical for the iterative design and compensation algorithm. In order to address these modeling limitations, the slot-tooth region and longitudinal end effect are included in the model. Then, its accuracy is verified by comparing the results with those of the 3-D time stepping finite element method (TSFEM). Then, the developed model is employed for design optimization to compensate for the end effects. Finally, the optimal sensor is experimentally prototyped and tested.

Abstract Background Chronic myeloid leukemia (CML) is a multifactorial clonal myeloid neoplasm that mainly arises from the Philadelphia chromosome. Even though imatinib mesylate (IM) is considered the gold standard for first-line treatment, a number of CML patients have shown IM resistance that can be influenced by many factors, including pharmacogenetic variability. The present study examined whether two common single nucleotide polymorphisms (SNPs) of ABCG2 (G34A and C421A) contribute to IM resistance and/or good responses. Material and methods A total of 72 CML patients were genotyped with high-resolution melting (HRM) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). We also determined the cytogenetic and hematological response, as evaluable factors for measuring response to imatinib. Results In the current study, we explored the relationship between the different variants of ABCG2 G34A and C421A and clinical response to imatinib among CML patients. There were no statistically significant differences between genotypes of C421A and G34A and allele frequencies among the resistant and responder groups, with response to IM (P > 0.05). Also, we found no statistically significant association between genotypes and cytogenetic and hematological responses. Conclusion This is the first study to investigate the association between genotypes of the G34A and C421A SNPs and the outcome of IM treatment in Iranian population. As a whole, genotyping of these SNPs is unhelpful in predicting IM response in CML patients.

Objective(s): This study aims to evaluate the in vivo anticancer activity of arginine-reduced graphene (Gr-Arg) and ginsenoside Rh2-containing arginine-reduced graphene (Gr-Arg-Rh2). Materials and Methods: Thirty-two mice with breast cancer were divided into four groups and treated every three days for 32 days: Group 1, PBS, Group 2, Rh2, Group 3, Gr-Arg, and Group 4, Gr-Arg-Rh2. The tumor size and weight, gene expression (IL10, INF-γ, TGFβ, and FOXP3), and pathological properties of the tumor and normal tissues were assessed. Results: Results showed a significant decrease in TGFβ expression for all drug treatment groups compared with the controls (P=0.04). There was no significant difference among the groups regarding IL10 and FOXP3 gene expression profiles (P>0.05). Gr-Arg-Rh2 significantly inhibited tumor growth (size and weight) compared with Rh2 and control groups. The highest survival rate and the highest percentage of tumor necrosis (87.5%) belonged to the Gr-Arg-Rh2 group. Lungs showed metastasis in the control group. No metastasis was observed in the Gr-Arg-Rh2 group. Gr-Arg-Rh2 showed partial degeneration of hepatocytes and acute cell infiltration in the portal spaces and around the central vein. The Gr-Arg group experienced a moderate infiltration of acute cells into the port spaces and around the central vein. The Rh2 group also showed a mild infiltration of acute and chronic cells in portal spaces. Conclusion: Based on the results, Gr-Arg-Rh2 can reduce tumor size, weight, and growth, TGF-β gene expression, and increase tumor necrosis and survival time in mice with cancer.

Abstract Using multiple position sensors in the control system of Two‐Degrees of Freedom (2‐DOF) motors causes it more complicated than that of conventional 1‐DOF ones. However, employing a 2‐DOF position sensor in comparison with two independent sensors, reduces the complexity, mass and volume of the system. The common 2‐DOF sensors are able to determine the position in linear, rotational, and helical motion. Yet, they suffer from accuracy reduction due to the longitudinal end effect. Therefore, analytical modelling and the relevant compensation methods are discussed. The accuracy of the model is approved by comparing its results with those of 3D time transient finite element method. Afterwards, the model is used for compensating the end effects. Finally, the optimised 2‐DOF resolver is prototyped and tested. The result of experimental test shows the proposed resolver's success.

Background: There are still conflicting results on thepostoperative consequences of patients with hip and femoralfractures based on the type of anesthesia. The aim of this studywas to compare mortality and morbidity of general and spinalanesthesia in patients undergoing hip and femoral fractures.Methods: In this analytical cross-sectional study, the informationof 93 patients who had undergone hip and femoral surgery withgeneral and spinal anesthesia was studied during 2011-2019 inthe medical records by census method. Data were analyzed usingSPSS 23 software and descriptive and analytical statistics.Results: The general anesthesia group consisted of 29 patientsand the spinal anesthesia group included 64 patients. The twogroups were the same in terms of demographic information,preoperative hemodynamic variables, and previous medicalhistory. The results of the independent t-test with a significancelevel of 5% did not show a significant difference between thetwo groups in the following variables: mean duration of surgeryand duration of anesthesia, mean arterial pressure and heartrate after surgery, changes in blood pressure, and heart rateduring surgery, bleeding, intravenous fluids and blood productsintake, postoperative hemoglobin, number of days hospitalizedin the Intensive Care Unit and surgical ward. The mean postoperative mean arterial pressure score in the general anesthesiagroup was significantly higher than the spinal group (P=0.004).Complications and mortality after surgery did not differ betweenthe two types of anesthesia.Conclusion: In general, these two methods of anesthesia do notdiffer from each other in terms of postoperative complications andmortality, and physicians can choose the appropriate anesthesiamethod according to the specific conditions of the patients

Immune system disorders and increased inflammation in the male reproductive system can lead to fetal risk in the early stages of development and implantation. Antioxidants such as vitamin C can play a protective role against sperm inflammatory reactions. This study aimed to evaluate the effect of vitamin C on the expression of inflammatory and anti-inflammatory cytokine genes in the male partners of couples with recurrent pregnancy loss. In this randomized clinical trial, twenty male partners of couples with RPL were examined for sperm parameters and expression profile of some inflammatory and anti-inflammatory cytokine genes before and after treatment with vitamin C. There was a statistically significant higher rate of normal morphology and sperm concentration in each patient before and after treatment with vitamin C p≤0.05. The mRNA levels of interleukin 6 and tumor necrosis factor-alpha were significantly decreased in the sperm of patients after treatment with vitamin C compared to before treatment. In contrast, the gene expression levels of interleukin 4 and transforming growth factor-beta showed a significant increase in the sperm of patients after treatment with vitamin C. Oral daily administration of vitamin C may be effective in the fertility potential of male partners of couples with RPL not only through the improvement of the sperm parameters but also by modulating the expression profile of inflammatory and anti-inflammatory genes. Further studies on protein levels are needed to clarify the role of TNF-⍺ and IFN-γ as a prognostic value in evaluating the recurrent abortion risk in infertile male partners. This trial is registered with IRCT20180312039059N1.

The aims of this study are to investigate the effect of acrylamide on the level of proinflammatory cytokines in the blood of acrylamide-treated rats and to find the modulatory impact of probiotics on those cytokines. Thirty-two rats were divided into four groups: rats which received 20 mg acrylamide, acrylamide with 20 mg probiotics, acrylamide with 200 mg probiotics, and standard water and food (groups 1–4, respectively). The serum levels of cytokines were measured on days 0, 15, and 30. Group 1 showed an increased serum level of IL-1β, IL-6, and TNF-α after 15 days, and they decreased in day 30. Serum IL-6 level was significantly decreased on days 15 and 30 in rats in group 2 compared to the controls. TNF-α and IL-1β levels were not statistically different after treated with probiotics. The exposure of rats to acrylamide led to increased systemic inflammation as evidenced by higher levels of proinflammatory cytokines, and probiotics can modulate this inflammation.

Background: The cervical spine is the most vulnerable part of the vertebral column and the rotational movements are the most dangerous movements which may cause damages to cervical spine. A good treatment option for the cervical disc disease is the replacement of a damaged disc with an artificial disc that has shown satisfactory clinical results. Methods: The C4 to C6 vertebrae of a normal subject and a person with an artificial disc between the vertebrae C5 and C6 were 3d modelled and then analyzed using FEM. The results of stress and deformation in both subjects were calculated and compared for three rotational head movements: axial rotation, flexion and extension. A distributed load of 73.6 N was used to simulate the head weight and a moment of 1.8 N.m was used to create all three rotational movements. Results: The maximum Von Mises stress in the normal subject during the axial rotation was respectively 2.2 and 1.8 times greater than the maximum stress during flexion and extension. These numbers were 2.6 and 2.3 in the subject with artificial disc. Following the artificial disc replacement, the cervical spine strength against the extension improved about 2.7%, however, the strength in axial rotation and flexion decreased 6.9% and 24.3%, respectively. The maximum values of deformation in the normal subject during flexion, extension and axial rotation were 2.8, 2.8 and 2 times of the values in the subject with artificial disc during the similar movements. Conclusion: The flexion and extension involve risks of hurting the cervical spine, however, the axial rotation is much more dangerous regarding the damages it may cause especially to the C5/6 intervertebral disc. Numerically, there is a much greater possibility of cervical spine injury during axial rotation.

Background: Cervical spine sustains most of the vertebral column injuries, among other injuries, the disc degeneration and damage that lead to replacement of the damaged disc with cage or artificial disc. Methods: The C4 to C6 vertebrae of a normal subject and a person with interbody fusion cage were 3d modelled and then analyzed using Finite element method. The results of maximum stress and strain in cervical spine of the normal subject and patient were compared in three positions: standing, lying with axial rotation of neck and standing with axial rotation of neck. Results: The maximum principal strain and stress in the patient are respectively 10.5% and 14.5% greater than those in normal subject in standing position, however in lying position when the head has axial rotation, the maximum principal strain and stress are in the normal subject 6.2% and 16.3% greater than those in patient, respectively. The difference between these results and the results of strain and stress in standing position when the head has axial rotation is very small. This outcome is due to smallness of the stress exerted on cervical spine as a result of the head weight (131-150 Pa). Conclusion: In contrary to the constraint between disc and vertebrae, there is no friction between cage and vertebrae and this leads to maximum stress transfer to the first vertebra above the cage in patient. However, the maximum stress is ultimately less in the patient with fusion cage than the normal subject. Generally, only the neck rotations are the cause of cervical spine injury in normal neck movements.

In this paper an efficient three- stage algorithm is developed for software production cost and time estimation. First stage includes a hybrid model composed of COCOMO and Function Points methods to increase estimation accuracy. Second stage encompasses paired comparisons matrix of analytical hierarchy process to determine amount of any resources consumed in each step of software production by experts’ opinions. Third stage concludes cost and time tables of production scheduling by using Work break structure (WBS) and network models of project control. In whole of all stages of this paper, triangular fuzzy numbers are used to express uncertainty existed in succession and repetition of each production step, time of beginning, ending, the duration of each task and costs of them. Retrieved results examined by 30 practical projects conclude accuracy of 93 percent for time estimation and 92 percent for cost one. Also suggested algorithm is more accurate than COCOMOІІ 2000 algorithm as 50 percent based on examined problems.

Purpose: Breast cancer is the most common cause of cancer-related death in women worldwide. Therefore, there is an urgent need to identify and develop therapeutic strategies against this deadly disease. This study is the first to investigate the cytotoxic effects and the mechanism of cell death of Scrophularia oxysepala extracts in MCF-7 human breast cancer cells. Methods: Three extracts of Scrophularia oxysepala including the n-hexane, dichloromethane and methanol extracts were examined. MTT (3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Trypan-blue assays were performed in MCF-7 cells as well as Human umbilical vein endothelial cells (HUVEC) to analyze the cytotoxic activity of the extracts of Scrophularia oxysepala. Further, the apoptosis inducing action of the extracts was determined by TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) test and cell death assay. Results: The results showed that the n-hexane extract had no cytotoxic effects but dichloromethane and methanol extracts significantly inhibited cell growth and viability in a dose and time dependent manner without inducing damage to non-cancerous cell line HUVEC. In addition, Cell death assay and DNA fragmentation analysis using TUNEL indicated induction of apoptosis by dichloromethane and methanol extracts of Scrophularia oxysepala in MCF-7 cells. Conclusion: Our studies suggest that this plant may contain potential bioactive compound(s) for the treatment of breast cancer.

Background and Objectives: Several factors may be the basis of intimate partner violence (IPV) and psychological distress of female victims, among which the role of positive concepts in such relationships is not very clear. Therefore, the present study was conducted with the aim of determining the model of the role of self-compassion and compassion for the romantic partner (CR) in psychological distress with the mediation of intimate partner violence (IPV) in female victims. Materials and Methods: The present study is descriptive. The statistical population included all women victims of IPV in Kerman province in 2023 (Kerman and Rafsanjan Cities) in 2022-2023, out of which 301 women were selected by convenience sampling. Revised Conflict Tactics Scale (CTS), Self-Compassion Scale (SCS), Compassionate Goals Scale (CGS), and Depression, Anxiety, and Stress Scale (DASS) were used for gathering data. Data were analyzed through structural equation modeling (SEM). Results: The results showed that there is a relationship between psychological distress and self-compassion, CR, and IPV with rates of -0.544, 0.153, and 0.332, respectively (p<0.05). There was a significant relationship between IPV and self-compassion and CR with the rate of -0.363 and 0.193 (p<0.05). Also, the results showed that there is a relationship between self-compassion and CR and psychological distress and mediation of IPV with rates of -0.121 and 0.064 (p<0.05). Conclusion: Results of the present study suggested that self-compassion in women who are victims of IPV can have positive consequences, but CR can increase IPV and, as a result, more psychological distress. Therefore, the results of this research highlight the different effects of positive concepts in traumatic relationships. [ABSTRACT FROM AUTHOR]