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Wound healing is a major problem in diabetic patients, and current treatments have been confronted with limited success. The present study examined the benefit of Wharton's jelly mesenchymal stem cells (WJ-MSCs) derived from the human umbilical cord (UC) in wound healing in diabetic rats. Thirty days after inducing diabetes, a circular excision was created in the skin of rats, and the treatments were performed for 21 days. Two groups were studied, which included the Control group and WJ-MSCs group. The studied groups were sampled on the 7th, 14th, and 21st days after wounding. Histological ultrasound imaging of dermis and epidermis in the wound area for thickness and density measurement and skin elasticity were evaluated. Our results on post-wounding days 7, 14, and 21 showed that the wound closure, thickness, and density of new epidermis and dermis, as well as skin elasticity in the healed wound, were significantly higher in the WJ-MSCs group compared to the Control group. Subcutaneous administration of WJ-MSCs in diabetic wounds can effectively accelerate healing. Based on this, these cells can be used along with other treatment methods in the healing of different types of chronic wounds.

The mist bioreactor has been proved to have a higher performance relative to the liquid phase reactor. The water and conventional media (MS, ½MS, and B5) were tested in a mist bioreactor to evaluate the performance of the misting system. The physicochemical properties of liquids were measured at 0 (Fresh state) and when treated by ultrasonic system for 1 and 2 h. At a given airflow rate, the misting rate for different heights of various media was determined. The results demonstrated that the electrical conductivity of all media increased with the duration of sonication. The ultrasonic effect caused an increase in surface tension of MS and ½MS, while the pH of MS and ½MS reduced with ultrasonic treatment. The inverse trends were observed for water and B5 for these properties. The misting rate increased by increasing liquid height to a maximum value, then decreased to a minimum value at the highest height. For all liquids studied in this experiment, this maximum value of misting performed at height ranged between 3 and 4 cm. The maximum and minimum values of the ultrasonic misting rate belonged to MS ( $$2.78\times {10}^{-2} g/s$$ ) at height 3 cm and B5 ( $$0.52\times {10}^{-2}g/s$$ ) at height 1 cm, respectively.

In this paper, small scale resistance seam welding (SSRSEW) of 304 stainless steel sheet with a thickness of 0.1 mm with a capacitor discharge (CD) welding machine is investigated. The effect of the main parameters such as discharged energy, electrode force, and electrode speed on the quality of the weld seam was investigated. In order to control the speed of the electrode, the electrode wheel was mounted on a CNC machine. Mechanical tests such as tensile-shear and peel tests were used to evaluate the quality of the weld seam. Also, the failure modes were investigated in different welding conditions. The results show that the discharged energy has more effect on the weld seam strength and the maximum strength in the peel test is usually lower than the strength of the tensile-shear test. Also, discharge energy level of 14 ws and electrode force of 20 N and electrode speeds of 200 and 300 mm/min are the optimum welding condition for welding the 304 stainless steel sheets with a thickness of 0.1 mm.

Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic agent for chronic wounds. There is no evidence regarding effectiveness of the spray and local transfer of this cellular product in diabetic wound healing. Accordingly, the present study, using clinical, pathological and biometric parameters, investigated the effectiveness of the spray of these cells in the healing of diabetic wounds in rats.Three days after the induction of diabetes (50 mg/kg single dose of streptozotocin) a circular excision was created on the back of rats. Diabetic rats were divided into two groups (n = 21): Control and WJ-MSCs group. Sampling of the studied groups was performed on Days 7, 14, and 21 after wounding. Histological, ultrasound imaging of dermis and epidermis in the wound area for thickness and density measurement and skin elasticity were evaluated.Our results on Days 7, 14, and 21 after wounding showed that the wound closure, thickness, and density of new epidermis and dermis, as well as skin elasticity in healed wound were significantly higher in WJ-MSCs group compared with the Control group.Application of WJ-MSCs suspension spray on the wound area can accelerate healing in diabetic wounds. Our findings may potentially provide a helpful therapeutic strategy for patients with a diabetic wound.

Statement of Novelty. Esophageal cancer is one of the most common types of cancer globally. Nowadays, Lactobacilli with probiotic potency is a preventing factor in cancer and many diseases. The anti-tumor properties of these bacteria have been indicated in various studies. Objective. This study is aimed at investigating the effect of probiotic Lactobacillus rhamnosus on esophageal cancer in vivo and in vitro. Methods and Results. In this study, the cytotoxicity effects of L. rhamnosus supernatant and whole-cell culture on a cancer cell line (Kyse30) compared to 5fu were evaluated by the MTT assay. The real-time PCR method was used to analyse the L. rhamnosus supernatant effect on the expression of Wnt signaling pathway genes. An in vivo investigation in nude mice was done to assess the anti-tumor activity of L. rhamnosus supernatant and whole-cell culture. Both supernatant and whole-cell culture of L. rhamnosus reduced cell survival (Kyse30) P < 0.001 . The supernatant of this bacterium significantly reduced the expression of Wnt signaling pathway genes. Administration of supernatant and whole-cell culture of L. rhamnosus expressively reduced tumor growth compared to the control group. The effects of this bacterium on tumor necrosis were quite evident, pathologically P < 0.01 . Conclusion. This study is the first report that assessed the potential impact of L. rhamnosus, especially its supernatant on esophageal cancer and Wnt signaling pathway genes. Therefore, this bacterium can be a harmless candidate for esophageal cancer therapy.

Background Despite significant advancements in breast cancer therapy, novel drugs with lower side effects are still being demanded. In this regard, we investigated the anti-cancer features of verbascoside in 4 T1 mouse mammary tumor cell. Methods First, MTT assay was performed with various concentrations (ranging between 5 to 200 μM) of verbascoside and IC50 was calculated. Then the expression of Bax, Bcl-2, and caspase-3 was evaluated in treated 4 T1 cells. In addition, we investigated the expression of TLR4, MyD88, and NF-κB to ascertain the underlying mechanism of the anti-proliferative feature of verbascoside. Also, flow cytometry followed by double PI and Annexin V was conducted to confirm the apoptosis-inducing effect of verbascoside. Results Our results from MTT assay showed verbascoside inhibits proliferation of 4 T1 cancer cells (IC50 117 μM) while is safe for normal HEK293T cells. By qRT-PCR, we observed that verbascoside treatment (100, 117 and, 130 μM) increases the expression of caspase-3 and Bax while reduces the expression of Bcl-2. Also, verbascoside (100, 117 and, 130 μM) increased the expression of TLR4 only at 130 μM dose and the expression of MyD88 whereas reduced the expression of NF-κB at mRNA level. Flow cytometry analysis also confirmed verbascoside induces apoptosis in 4 T1 cells at 117 μM. Conclusion Taken together, our data showed verbascoside is a safe natural compound for normal cells while has apoptosis-inducing feature through TLR4 axis on 4 T1 cells.

Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy. We sought to assess the association of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) candidate polymorphisms with drug-resistant epilepsy among Iranian children with epilepsy.In a hospital-based case-control study, 93 participants, including 45 men and 48 women aged 1.5 to 14 years old were recruited. Genotyping of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) polymorphisms using the high-resolution melting (HRM) method were measured in 46 children with drug-resistant epilepsy and 47 healthy control subjects. The binary logistic regression model was used to estimate the odds ratio (OR) for each polymorphism per effect allele increase.The mean (standard deviation [SD]) age of the drug-resistant patients was 10.7 (9.0) years versus 7.3 (3.6) in the control group. In the case group, most of the patients with epilepsy were diagnosed with generalized seizure (about 87%) and negative epileptic history status (63%). Furthermore, idiopathic epilepsy was dominant in the case group (69%). There was a clinically meaningful increase in the chance of drug-resistant epilepsy in participants with candidate polymorphism in ABCG2 gene (per allele T increase, adjusted odds ratio [OR] 2.41, confidence interval [CI] 0.99 to 5.87, P=0.05). No significant association was found between CYP3A5 (per allele C increase, OR 0.92, CI 0.33 to 2.60, P= 0.88) and SCN1A (per allele *1 increase, OR 0.65, 95% CI 0.34 to 1.23, P= 0.19) with drug-resistant epilepsy.We found evidence for the relationship between the ABCG2 gene polymorphism and a higher chance of drug-resistant epilepsy in children. This finding may have important implications for understanding the role of ABCG2 gene polymorphism in children with drug-resistant epilepsy.

Dentate gyrus (DG) has a high density of 5-HT1A receptors. It has neural nitric oxide synthase (nNOS), which is involved in neural excitability. The purpose of this study was to investigate the role of 5-HT1A receptors and nNOS of DG in perforant path kindling model of epilepsy.To achieve this purpose, a receptor antagonist (WAY100635, 0.1 mg/kg, intracerebroventricular, i.c.v) and neuronal nitric oxide synthase inhibitor (7-NI, 15 mg/kg, intraperitoneal, i.p.) were injected during kindling aquisition. Adult male Wistar rats (280 ± 20 g) were used in this study Animals were kindled through the daily administration of brief electrical stimulations (10 stimulations per day) to the perforant pathway. Field potential recordings were performed for 20 min in DG beforehand. Additionally, glial fibrillary acidic protein (GFAP) expression rate in the DG was determined using immunohistochemistry as a highly specific marker for glia.WAY100635 (0.1 mg/kg) significantly attenuated the kindling threshold compared to the kindled + vehicle group (P 0.001). The co-administration of WAY100635 with 7-NI, exerted a significant anticonvulsive effect. Furthermore, the slope of field Excitatory Post Synaptic Potentials (fEPSP) at the end of 10 days in the kindled + 7-NI + WAY100635 group was significantly lower than in the kindled + vehicle group (P 0.001). Furthermore, immunohistochemistry showed that the density of GAFPOur data demonstrate that antagonists of 5-HT1A receptors have proconvulsive effects and that astrocyte cells are involved in this process, while nNOS has an inhibitory effect on neuronal excitability.

Natural phenolic compounds have inhibition effects on various malignancies. Thymol is one of these compounds present in several plant sources such as ajowan (Trachyspermum ammi) fruits. In this study, thymol was evaluated for its potential cytotoxic activity as well as its effect on apoptotic gene expression in breast cancer cell line. We used the GC-MS technique to identify the essential oil constituents of ajowan. MCF-7 cells were treated by various concentrations of thymol and half maximum inhibitory concentration (IC50) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, morphological alterations and changes of P21, P53 and Mcl-1 gene expression in MCF-7 cells were investigated by microscopic examination and real-time RT-PCR assay. Data from MTT assay indicated that the IC50 values of thymol on MCF-7 cells for 48 h and 72 h were 54 and 62 μg/mL, respectively. Furthermore, this compound significantly affected gene expressions of P53 and P21, but not Mcl-1. Thymol can induce the apoptosis process in MCF-7, and hence it can be considered an anticancer agent in the future.

Data Envelopment Analysis (DEA) is a widely used technique for measuring the relative efficiencies of Decision Making Units (DMUs) with multiple deterministic inputs and multiple outputs. However, in real-world problems, the observed values of the input and output data are often vague or random. Indeed, Decision Makers (DMs) may encounter a hybrid uncertain environment where fuzziness and randomness coexist in a problem. Hence, we formulate a new DEA model to deal with fuzzy stochastic DEA models. The contributions of the present study are fivefold: (1) We formulate a deterministic linear model according to the probability–possibility approach for solving input-oriented fuzzy stochastic DEA model, (2) In contrast to the existing approach, which is infeasible for some threshold values; the proposed approach is feasible for all threshold values, (3) We apply the cross-efficiency technique to increase the discrimination power of the proposed fuzzy stochastic DEA model and to rank the efficient DMUs, (4) We solve two numerical examples to illustrate the proposed approach and to describe the effects of threshold values on the efficiency results, and (5) We present a pilot study for the NATO enlargement problem to demonstrate the applicability of the proposed model.

A set of jobs has to be processed on parallel machines. For each job, there are given a release time and a due date and the job must be processed no later than its due date. If the job will be comp ...

Data envelopment analysis (DEA) is a widely used mathematical programming technique for measuring the relative efficiency of decision-making units which consume multiple inputs to produce multiple outputs. Although precise input and output data are fundamentally used in classical DEA models, real-life problems often involve uncertainties characterized by fuzzy and/or random input and output data. We present a new input-oriented dual DEA model with fuzzy and random input and output data and propose a deterministic equivalent model with linear constraints to solve the model. The main contributions of this paper are fourfold: (1) we extend the concept of a normal distribution for fuzzy stochastic variables and propose a DEA model for problems characterized by fuzzy stochastic variables; (2) we transform the proposed DEA model with fuzzy stochastic variables into a deterministic equivalent linear form; (3) the proposed model which is linear and always feasible can overcome the nonlinearity and infeasibility in the existing fuzzy stochastic DEA models; (4) we present a case study in the banking industry to exhibit the applicability of the proposed method and feasibility of the obtained solutions.

To assess the effect of an acidic beverage (Orange juice) on the change in serum Phenobarbital concentrations in children with seizure who take Phenobarbital as the main treatment.We did a parallel design and placebo controlled randomized clinical trial. Patients attending Heshmatiyeh Hospital (Iran) were recruited from October 2016 to December 2017. Forty patients randomly assigned to either experimental group or control group. Firstly, 5 mL blood sample was taken from both groups to measure serum Phenobarbital concentration before experiment. Then, one oral dose of Phenobarbital (2.5 mg/kg) with 100 mL of corporate Orange juice (pH = 3.5) (experiment group) or 100 mL of mineral water (neutral pH) (control group) was given to each group, respectively. After 2 h of administration, another blood sample was taken. The high-performance liquid chromatographic system was used for measurement of serum Phenobarbital concentration.There was significant increase in serum Phenobarbital concentrations after taking Phenobarbital in experiment group in comparison to control group. Statistical analysis revealed a significant increase in change of serum Phenobarbital concentrations in experiment group versus control group.The results of the current trial indicate that the level of serum Phenobarbital in the experiment group was higher than that of control group.

We address a generalization of the classical job-shop problem which is called a hybrid job-shop problem. The criteria under consideration are the minimization of the makespan and mean flow time. In the hybrid job-shop, machines of type [Formula: see text] are available for processing the specific subset [Formula: see text] of the given operations. Each set [Formula: see text] may be partitioned into subsets for their processing on the machines of type [Formula: see text]. Solving the hybrid job-shop problem implies the solution of two subproblems: an assignment of all operations from the set [Formula: see text] to the machines of type [Formula: see text] and finding optimal sequences of the operations for their processing on each machine. In this paper, a genetic algorithm is developed to solve these two subproblems simultaneously. For solving the subproblems, a special chromosome is used in the genetic algorithm based on a mixed graph model. We compare our genetic algorithms with a branch-and-bound algorithm and three other recent heuristic algorithms from the literature. Computational results for benchmark instances with 10 jobs and up to 50 machines show that the proposed genetic algorithm is rather efficient for both criteria. Compared with the other heuristics, the new algorithm gives most often an optimal solution and the average percentage deviation from the optimal function value is about 4%.

Data envelopment analysis (DEA) is a widely used technique for measuring the relative efficiencies of decision-making units (DMUs) with multiple inputs and multiple outputs. The classical DEA models were initially formulated only for desirable inputs and outputs. However, undesirable outputs may be present in the production process which needs to be minimized. In addition, in real-world problems, the observed values of the input and output data are often vague or random. Indeed, decision makers may encounter a hybrid uncertain environment where fuzziness and randomness coexist in a problem. In order to deal with the above problems, this paper proposes fuzzy stochastic DEA model with undesirable outputs. Three fuzzy DEA models with respect to probability–possibility, probability–necessity and probability–credibility constraints are applied. The contribution of this paper is fourfold: (1) the proposed approach considers the impact of undesirable outputs on the performance of DMUs; (2) unlike the existing methods, the proposed solution approach provides efficiency scores in the range of zero and one for all DMUs; (3) the proposed approach analyzes the influence of the presence of both fuzzily imprecision and probabilistic uncertainty in the data over the efficiency results; and (4) a case study in the banking industry is presented to exhibit the efficacy of the procedures and demonstrate the applicability of the proposed model.

There are many pieces of evidence support the effect of cancer stem cells on the initiation and progression of cancer. However, related mechanisms involved in these phenomena are far more complicated to understand. The function of different stemness factorsin cancer stem cells (CSCs) and their complex associations at different levels of cancer have been reported. Therefore, it seems that focusing on one master factor would be more helpful to complete the puzzle of singling pathways in these cells. Octamer-binding transcription factor 4 (OCT4) also known as POU domain, class 5, transcription factor 1(POU5F1), one of these key pluripotency factors, has important roles in both embryogenesis and tumorigenesis. In this review, we gathered information about the association of different markers with OCT4 expression in three types of gastrointestinal cancers including esophageal, gastric and colorectal cancers. OCT4 through different signaling pathways has an impact on different processes of gastrointestinal cancers such as proliferation, invasion, and metastasis. Based on the literature, OCT4 has great effects on cancer progression at different stages, therefore we suggested it has potential implications in therapeutic options.

Aim: Oral health is among the important components of individual general health that affects the health of entire body. This study aims at investigating the effect of educational intervention on the primary school students' oral health.Methods: This quasi-experimental study was conducted on 175 primary school students recruited randomly from different regions of Dehloran City during the school year of 2014-15. The testimonial was obtained after holding briefings for the parents. Data were collected using a researcher-made questionnaire, which was administrated at baseline and 3 months after the intervention. The content validity was approved by the expert panel and its reliability was confirmed by Cronbach's alpha coefficient. Data were analyzed by SPSS software 18, inferential statistical tests, and paired t-test. This study was supported by the HSR Council and the Ethics Committee of Ilam University of Medical Sciences.Findings: The results indicated significant changes in the samples' knowledge (from 3.6±1.37 to 4.98± 1.57), attitude (from 28.17±5.7 to 30.98±6.35) and behavior (15.03 ±2.98 to 17.08 ±2.60) after the intervention.Conclusion: The positive results of educational intervention indicate that the education through appropriate methods can improve students' behavior in the field of oral health. Therefore, it is suggested more emphasis on oral health education at school age.

Background: Ferula assa-foetida is a herbaceous plant of the Umbelliferae family having a broad spectrum of biological activities such as antiseptic, antibacterial, anti-inflammation, and, anti-tumor activity against a wide range of cancers. Among these features, antitumor activity has become more important in recent years and it still demands more investigations to address the underlying mechanisms. Purpose: This current study was conducted to evaluate the anti-proliferative effect of Ferula assa-foetida on PC12 and MCF7 cells as well as examining its mechanisms. Materials and Methods: Cells were cultured in DMEM medium with 10% fetal bovine serum, 100 units/ml penicillin, and 100 µg/ml streptomycin. Cells incubated with different concentrations of the ethanolic extract of Ferula assa-foetida. Notably, cytotoxicity and apoptosis assay were measured by MTT and PI staining, respectively. Results: The MTT results showed that the ethanolic extract of Ferula assa-foetida in concentrations of 10, 7, 5, and 2.5 μM on both PC12 and MCF7 cells had a significant effect in cell viability and apoptosis induction in comparison to control group. Conclusion: In this study, it was determined that Ferula assa-fetida through the induction of apoptosis prevented the growth of PC12 and MCF7 cells and made a reduction in cell viability with different concentrations in a time- and dose-dependent manner. However, more studies are needed to reveal the mechanisms of Ferula assa-foetida’s extract in apoptosis induction.

Heuristic algorithms are developed to solve the parallel-machine job-shop problems , where the criterion is the minimisation of the makespan, , or the sum of completion times, . The developed algorithms include sequencing and assigning stages. At the sequencing stage, the job-shop problem is solved, where job is available for processing from time . The problem is modelled by a mixed graph , where the vertices are the operations to be processed. The precedence constraints on the set are determined by the arc set . The resource constraints are determined by the edge set . In order to resolve a conflict arising between two operations processed on the same machine, the algorithm should substitute a conflict edge from the set by an arc incident to the same vertices from the set . The resulting digraph determines a heuristic solution to the problem , where all machines are different. The digraph determines a semi-active schedule for the problem . A mixed graph model is used for solving the problem , which allow...

In this paper, the effect of cathode flow field geometry on a passive direct methanol fuel cell (DMFC) performance at various concentrations of methanol is studied. Three cells with perforated current collector, parallel channels and trapezoidal channels with opening to downward current collector at the cathode side are tested at 2 to 5 molar concentrations of methanol. In order to maintain equal conditions on the anode side, the trapezoidal channels with opening to upward is used in all three cells. By placing the cathode flow field pattern on the anode flow field pattern, four zones are defined and the role of these areas on the performance of each cell at concentrations of 2 to 5 molar are investigated. It is found that the zones where the anode’s open area placed directly in front of the cathode’s open area has a considerable effect on the methanol cross over, and also the zones which anode and cathode current collector’s walls placed on each other has more effect on the amount of surface contact.

We consider the FJ?C max problem of optimal servicing with respect to performance for a given set of jobs by sequential and parallel machines. The problem FJ?C max is a generalization of the classical J?C max problem for the case when the servicing system has not only sequential but also parallel (identical) machines. We propose a two-stage algorithm for a heuristic solution of problem FJ?C max On the first stage, we solve the problem J?C max, i.e., we assume that the servicing system does not have parallel machines. On the second stage, operations are distributed over parallel machines. On both stages of the algorithm, we use neural network decision making models. The efficiency of a neural network algorithm for the problem J?C max and problem FJ?C max was evaluated on 20 test examples obtained from 20 known J?C max problems by including into the servicing system a random number of copies of sequential machines.

We consider a multistage processing system, which includes both identical (parallel) machines that can process the same set of operations and different machines that can process only different operation sets. A release time r i is given for each job J i to be processed. For such a processing system, we minimize the makespan, i.e., problem $IJ|r_i|C_{\max }$ is considered. The problem $IJ|r_i|C_{\max }$ is an extension of the classical job-shop problem $J|r_i|C_{\max }$ for the case when parallel (or identical) machines are also given. Both problems $J|r_i|C_{\max }$ and $IJ|r_i|C_{\max }$ are strongly NP-hard. A mixed graph model used for solving the problem $J|r_i|C_{\max }$ is generalized for the problem $IJ|r_i|C_{\max }$ . Using the mixed graph model, we developed a fast heuristic algorithm for solving the problem $IJ|r_i|C_{\max }$ . Computational experiments were conducted to evaluate the performance of the algorithm on the 22 benchmark instances and on the 40 new randomly generated instances of the problem $IJ||C_{\max }$ . For the small and moderate instances, the exact values of the objective function were compared with those calculated by the proposed heuristic algorithm. The average relative error was not greater than $2.4~\%$ for all instances with available optimal schedules. Computational results showed that the developed algorithm runs faster than some other heuristics being tested, and the schedules constructed by the developed algorithm have smaller makespans.

In this paper, the effects of current collector on passive direct methanol fuel cell's (passive DMFC) performance and removing CO 2 gas is studied. For this purpose, a single cell with two arrangements of current collector in anode and cathode side is considered. In first arrangement, non-uniform parallel channels with 53.76% open ratio is used in the anode side and a perforated flow field with 34.5% open ratio is applied in the cathode side. In second arrangement, uniform parallel channels with 42.28% open ratio has been used in both anode and cathode sides. At the first arrangement, a maximum power of 20 mW cm −2 in 4 M methanol concentrations and in the second arrangement a maximum power of 17.7 mW cm −2 in 5 M methanol concentrations has been obtained. Furthermore, it is shown that using the current collector with non-uniform parallel channels is more effective in removing CO 2 gas than other parallel channels.

A learning stage of scheduling tends to produce knowledge about a benchmark of priority dispatching rules which allows a scheduler to improve the solution quality for a set of similar job-shop problems. Once trained on the sample job-shop problems (usually with small sizes), the adaptive algorithm solves a similar job-shop problem (with a moderate size or a large size) better than heuristics used as a benchmark at the learning stage of scheduling. Our adaptive algorithm does not guarantee to perform as an exact algorithm or better than a more sophisticated heuristic algorithm (like e.g. the shifting bottleneck one) which need a large running time. For an adaptive algorithm with a learning stage, the job-shop scheduling problem is modeled via a weighted mixed (disjunctive) graph with the conflict resolution strategy used for finding an appropriate schedule.

Umbelliprenin is a prenylated compound, which belongs to the class of sesquiterpene coumarins. It is extracted from dried roots of Ferula szwitsiana collected from the mountains of Golestan forest (Golestan Province, north of Iran). Induction of apoptosis in Jurkat T-CLL cells has been previously shown. In this study, effect of umbelliprenin on proapoptotic caspases (caspase-8 and -9) and antiapoptotic Bcl-2 family protein was studied. Jurkat cells were incubated with umbelliprenin. Cells were then lysed and activation of proteins was studied by Western blot analysis. In this study, we showed that umbelliprenin activates intrinsic and extrinsic pathways of apoptosis by the activation of caspase-8 and -9 respectively. Inhibition of Bcl-2 was also shown. In conclusion, umbelliprenin induced apoptosis in Jurkat cells through caspase-dependent apoptosis pathway.

Induction of apoptosis in tumor cells is one of the mechanisms of chemotherapy. Myeloid cell leukemia type 1 is one of the Bcl-2 protein families that make an important role in chemo resistance to drugs. Thus down-regulation of myeloid cell leukemia type 1 gene is one of the aims in chemotherapy. Umbelliprenin and auraptene are naturally coumarins. Cytotoxicity and apoptosis induction is one of their effects. In this study we examined the cytotoxicity of these two coumarins against some cancerous cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay method and compare them together. In next step, we tested the effect of auraptene. On myeloid cell leukemia type 1 gene expression in Jurkat cells by real time polymerase chain reaction method. We found that umbelliprenin and auraptene. Have cytotoxic effect against cancerous cell lines. Auraptene is more cytotoxic than umbelliprenin. We also found that auraptene down-regulates myeloid cell leukemia type 1 gene expression in a pattern that different from umbelliprenin.

A problem of train timetabling for a single-track railway is studied using a disjunctive graph model for the corresponding job-shop. The objective is to minimize the total weighted tardiness of the given trains. A shifting bottleneck algorithm is developed and tested to get a close to optimal schedule to the job-shop problem. At each iteration, this algorithm tries to minimize the total weighted tardiness of jobs (trains) with the given release times (departure times of the trains), the due dates, and the processing times on a single machine (single-track section between two stations). Since the latter problem is unary NP-hard, a heuristic procedure is used at each iteration of the shifting bottleneck algorithm. Computational results demonstrate the dependence of the CPU-time on the number of trains and single-track sections.

Train timetabling is a complex and time-consuming problem, which must be solved accurately to gain maximum performance on using the resources of a railway company (railways, trains, staff, etc.). An appropriate time bill (a timetable) must have a low latency, suitable train routes and a minimum time for traveling passenger trains and freight trains. In this paper, a genetic algorithm for routing and scheduling trains is developed to achieve efficient and robust train routes and a timetable. The algorithm may change the start times of the trains with the aim to find better times for the trains to start their moving and to have less number and a smaller total time of possible train delays. The algorithm changes some parts of the train paths to the destination to have a less mutual exclusion to use railways if it is allowable for a train (e.g., freight trains and express passenger trains are not allowed to stop at some middle stations of their routes). Simulations on a computer show that the developed genetic algorithm can reduce the tardiness of the trains to go from a source station to a destination.

Chronic lymphocytic leukemia (CLL) remains an incurable disease that requires innovative new approaches to improve therapeutic outcome. Many Ferula species, including F. asa-foetida, synthesize terpenyloxy coumarins. One of these coumarins is umbelliprenin, which has been implicated with induction of apoptosis in some cancer cell lines. In this study induction of apoptosis by umbelliprenin on Jurkat T-CLL and Raji B-CLL cell lines was studied. In this regard, cells were incubated with various concentrations of umbelliprenin in-vitro for different times and assayed for apoptosis with annexin V-FITC/PI double staining flowcytometry method. Results showed that umbelliprenin induced apoptosis in leukemic cells in a dose- and time-dependent manner and that CLL cells were more susceptible to umbelliprenin induced cell death than normal peripheral blood mononuclear cell (PBMCs). Moreover, we study the induction of apoptosis in Jurkat cells by umbelliprenin in the presence of interleukin 4 (IL-4) as an agent that causes resistance to apoptosis in CLL cells, was also student. We showed that IL-4 can not reduce apoptotic effect of umbelliprenin. The preferential toxicity of umbelliprenin for CLL cells, supports the hypothesis that oral administration of umbelliprenin in the form of foods or folk medicines containing this coumarin, might enhance protection against the development of CLL in man with little side effects. In conclusion, umbelliprenin may be an effective therapeutic agent in the treatment of CLL, and thus clinical studies with umbelliprenin may be appropriate.