Abstract: Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. 43 children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by the World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children, whose BMI percentile values were between 99 and 95, comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analyses, including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %) and ferritin, were performed. sTWEAK levels were determined by enzyme-linked immunosorbent assay. study data were evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91 ± 34 mcrg/dl and 75 ± 31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs. 299 mcrg/dl, 37.2 ± 19.1% vs. 26.7 ± 14.6%, and 41 ± 25 ng/ml vs 44 ± 26 ng/ml. In N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p > 0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p < 0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is an inducer of apoptosis. OB children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of OB children.
Abstract: Tropaeolum majus L. is a native plant to South and Central America, used since ancient times by our ancestors to combat different diseases. Glucotropaeolonin is one of its main components, which when hydrolyzed, forms benzyl isothiocyanate (BIT) that promotes cellular apoptosis (programmed cell death in cancer cells). Therefore, the present research aims to evaluate the effect of the pressure and temperature of BIT extraction by supercritical CO2 from Tropaeolum majus L. The extraction was carried out in a supercritical fluid extractor equipment Speed SFE BASIC Brand: Poly science, the leaves of Tropaeolum majus L. were ground for one hour and lyophilized until obtaining a humidity of 6%. The extraction with supercritical CO2 was carried out with pressures of 200 bar and 300 bar, temperatures of 50°C, 60°C and 70°C, obtained by the conjugation of these six treatments. BIT was identified by thin layer chromatography using 98% BIT as the standard, and as the mobile phase hexane: dichloromethane (4:2). Subsequently, BIT quantification was performed by high performance liquid chromatography (HPLC). The highest yield of oleoresin by supercritical CO2 extraction was obtained pressure 300 bar and temperature at 60°C; and the higher content of BIT at pressure 200 bar and 70°C for 30 minutes to obtain 113.615 ± 0.03 mg BIT/100 g dry matter was obtained.
Abstract: 5-FU is a chemotherapeutic agent that has been used in colorectal cancer (CRC) treatment. However, it is usually associated with the acquired resistance, which decreases the therapeutic effects of 5-FU. miR-200c is involved in chemotherapeutic drug resistance, but its mechanism is not fully understood. In this study, the effect of inhibition of miR-200c in sensitivity of HCT-116 CRC cells to 5-FU was evaluated. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was evaluated using quantitative real- time PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were analyzed by western blotting. Annexin V and propidium iodide staining assay were applied for apoptosis detection. The caspase-3 activation was evaluated by an enzymatic assay. The results showed LNA-anti-miR-200c inhibited the expression of PTEN and E-cadherin protein, apoptosis and activation of caspase 3 compared with control cells. In conclusion, these results suggest that miR-200c as a prognostic marker can overcome to 5-FU chemoresistance in CRC.
Abstract: Radiation therapy is an effective vital strategy used globally in the treatment of cervical cancer. However, radiation efficacy principally depends on the radiosensitivity of the tumor, and not all patient exhibit significant response to irradiation. A radiosensitive tumor is easier to cure than a radioresistant tumor which later advances to local recurrence and metastasis. Herbal polyphenols are gaining attention for exhibiting radiosensitization through various signaling. Current work focuses to study the radiosensitization effect of ellagic acid (EA), on HeLa cells. EA intermediated radiosensitization of HeLa cells was due to the induction γ-H2AX foci formation, G1 phase cell cycle arrest, and loss of reproductive potential, growth inhibition, drop in the mitochondrial membrane potential and protein expression studies that eventually induced apoptosis. Irradiation of HeLa in presence of EA (10 μM) to doses of 2 and 4 Gy γ-radiation produced marked tumor cytotoxicity. EA also demonstrated radio-protective effect on normal cell, NIH3T3 and aided recovery from the radiation damage. Our results advocate EA to be an effective adjuvant for improving cancer radiotherapy as it displays striking tumor cytotoxicity and reduced normal cell damage instigated by irradiation.
Abstract: Harmalol administration caused remarkable reduction in proliferation of HepG2 cells with GI50 of 14.2 mM, without showing much cytotoxicity in embryonic liver cell line, WRL-68. Data from circular dichroism and differential scanning calorimetric analysis of harmalol-CT DNA complex shows conformational changes with prominent CD perturbation and stabilization of CT DNA by 8 oC. Binding constant and stoichiometry was also calculated using the above biophysical techniques. Further, dose dependent apoptotic induction ability of harmalol was studied in HepG2 cells using different biochemical assays. Generation of ROS, DNA damage, changes in cellular external and ultramorphology, alteration of membrane, formation of comet tail, decreased mitochondrial membrane potential and a significant increase in Sub Go/G1 population made the cancer cell, HepG2, prone to apoptosis. Up regulation of p53 and caspase 3 further indicated the apoptotic role of harmalol.
Abstract: Oxidative stress associated with semen cryopreservation may result in lipid peroxidation (LPO), DNA damage and apoptosis, leading to decreased sperm motility and fertilization ability. Curcumin (CUR), a natural phenol isolated from Curcuma longa Linn. has been presented as a possible supplement for a more effective semen cryopreservation because of its antioxidant properties. This study focused to evaluate the effects of CUR on selected oxidative stress parameters in cryopreserved bovine semen. 20 bovine ejaculates were split into two aliquots and diluted with a commercial semen extender containing CUR (50 μmol/L) or no supplement (control), cooled to 4 °C, frozen and kept in liquid nitrogen. Frozen straws were thawed in a water bath for subsequent experiments. Computer assisted semen analysis was used to evaluate spermatozoa motility, and reactive oxygen species (ROS) generation was quantified by using luminometry. Superoxide generation was evaluated with the NBT test, and LPO was assessed via the TBARS assay. CUR supplementation significantly (P
Abstract: Colorectal cancer (CRC) is one of the most prevalent cancers and intestinal microbial community plays an important role in colorectal tumorigenesis. Probiotics have recently been assessed as effective anti-proliferative agents and thus this study was performed to examine whether CRC undergo apoptosis by treating with isolated Iranian native dairy yeast, Kluyveromyces marxianus YAS, secretion metabolites. The cytotoxicity assessments on cells (HT-29, Caco-2) were accomplished through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as well as qualitative DAPI (4',6-diamidino-2-phenylindole staining) and quantitative (flow cytometry assessments) evaluations of apoptosis. To evaluate the main mechanism of apoptosis, Real time PCR method was applied. Kluyveromyces marxianus YAS secretions (IC50) showed significant cytotoxicity against HT-29 and Caco-2 cancer cell lines (66.57 % and 66.34 % apoptosis) similar to 5-Fluorouracil (5-FU) while apoptosis only was developed in 27.57 % of KDR normal cells. The prophylactic effects of Kluyveromyces marxianus (PTCC 5195), as a reference yeast, was not similar to Kluyveromyces marxianus YAS indicating strain dependency of bioactivities on CRC disease prevention. Based on real time PCR results, the main cytotoxicity is related to apoptosis phenomenon and the core related mechanism is depended on the overexpression of BAX, CASP 9, CASP 8 and CASP 3 inducing apoptosis genes. However, several investigations should be conducted to precisely determine the effective compounds to be used as anticancer therapeutics in the future.
Abstract: MicroRNAs are small non-coding RNA found in
many different species. They play crucial roles in cancer such as
biological processes of apoptosis and proliferation. The identification
of microRNA-target genes can be an essential first step towards to
reveal the role of microRNA in various cancer types. In this paper,
we predict miRNA-target genes for lung cancer by integrating
prediction scores from miRanda and PITA algorithms used as a
feature vector of miRNA-target interaction. Then, machine-learning
algorithms were implemented for making a final prediction. The
approach developed in this study should be of value for future studies
into understanding the role of miRNAs in molecular mechanisms
enabling lung cancer formation.
Abstract: Several embryonic cellular mechanism including cell
cycle, growth and apoptosis are regulated by phosphatidylinositol-3-
kinase (PI3K)/Akt signaling pathway. The goal of present study is to
determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol
(δ-TCT) on the regulations of PI3K/Akt genes in murine morula.
Twenty four 6-8 week old (23-25g) female balb/c mice were
randomly divided into four groups (G1-G4; n=6). Those groups were
subjected to the following treatments for 7 consecutive days: G1
(control) received tocopherol stripped corn oil, G2 was given 60
mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma
isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity)
and G4 received 60 mg/kg/day α-TOC. On Day 8, females were
superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin
(PMSG) for 48 hours followed with 5 IU human Chorionic
Gonadotropin (hCG) before mated with males at the ratio of 1:1.
Females were sacrificed by cervical dislocation for embryo collection
48 hours post-coitum. About fifty morulas from each group were
used in the gene expression analyses using Affymetrix QuantiGene
Plex 2.0 Assay. Present data showed a significant increase (p
Abstract: Array-based gene expression analysis is a powerful
tool to profile expression of genes and to generate information on
therapeutic effects of new anti-cancer compounds. Anti-apoptotic
effect of thymoquinone was studied in MCF7 breast cancer cell line
using gene expression profiling with cDNA microarray. The purity
and yield of RNA samples were determined using RNeasyPlus Mini
kit. The Agilent RNA 6000 NanoLabChip kit evaluated the quantity
of the RNA samples. AffinityScript RT oligo-dT promoter primer
was used to generate cDNA strands. T7 RNA polymerase was used to
convert cDNA to cRNA. The cRNA samples and human universal
reference RNA were labelled with Cy-3-CTP and Cy-5-CTP,
respectively. Feature Extraction and GeneSpring softwares analysed
the data. The single experiment analysis revealed involvement of 64
pathways with up-regulated genes and 78 pathways with downregulated
genes. The MAPK and p38-MAPK pathways were
inhibited due to the up-regulation of PTPRR gene. The inhibition of
p38-MAPK suggested up-regulation of TGF-ß pathway. Inhibition of
p38-MAPK caused up-regulation of TP53 and down-regulation of
Bcl2 genes indicating involvement of intrinsic apoptotic pathway.
Down-regulation of CARD16 gene as an adaptor molecule regulated
CASP1 and suggested necrosis-like programmed cell death and
involvement of caspase in apoptosis. Furthermore, down-regulation
of GPCR, EGF-EGFR signalling pathways suggested reduction of
ER. Involvement of AhR pathway which control cytochrome P450
and glucuronidation pathways showed metabolism of Thymoquinone.
The findings showed differential expression of several genes in
apoptosis pathways with thymoquinone treatment in estrogen
receptor-positive breast cancer cells.
Abstract: Artificial Immune Systems (AIS), inspired by the
human immune system, are algorithms and mechanisms which are
self-adaptive and self-learning classifiers capable of recognizing and
classifying by learning, long-term memory and association. Unlike
other human system inspired techniques like genetic algorithms and
neural networks, AIS includes a range of algorithms modeling on
different immune mechanism of the body. In this paper, a mechanism
of a human immune system based on apoptosis is adopted to build an
Intrusion Detection System (IDS) to protect computer networks.
Features are selected from network traffic using Fisher Score. Based
on the selected features, the record/connection is classified as either
an attack or normal traffic by the proposed methodology. Simulation
results demonstrates that the proposed AIS based on apoptosis
performs better than existing AIS for intrusion detection.
Abstract: Persea declinata (Bl.) Kosterm is a member of the
Lauraceae family, widely distributed in Southeast Asia. It is from the
same genus with avocado (Persea americana Mill), which is widely
consumed as food and for medicinal purposes. In the present study,
we examined the anticancer properties of Persea declinata (Bl.)
Kosterm bark methanolic crude extract (PDM). PDM exhibited a
potent antiproliferative effect in MCF-7 human breast cancer cells,
with an IC50 value of 16.68 .g/mL after 48h of treatment. We
observed that PDM caused cell cycle arrest and subsequent apoptosis
in MCF-7 cells, as exhibited by increased population at G0/G1 phase,
higher lactate dehydrogenase (LDH) release, and DNA
fragmentation. Mechanistic studies showed that PDM caused
significant elevation in ROS production, leading to perturbation of
mitochondrial membrane potential, cell permeability, and activation
of caspases-3/7. On the other hand, real-time PCR and Western blot
analysis showed that PDM treatment increased the expression of the
proapoptotic molecule, Bax, but decreased the expression of
prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner.
These findings imply that PDM could inhibit proliferation in MCF-7
cells via cell cycle arrest and apoptosis induction, indicating its
potential as a therapeutic agent worthy of further development.
Abstract: ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I transmembrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish
Abstract: MicroRNAs (miRNAs), a class of approximately 22 nucleotide long non coding RNAs which play critical role in different biological processes. The mature microRNA is usually 19–27 nucleotides long and is derived from a bigger precursor that folds into a flawed stem-loop structure. Mature micro RNAs are involved in many cellular processes that encompass development, proliferation, stress response, apoptosis, and fat metabolism by gene regulation. Resent finding reveals that certain viruses encode their own miRNA that processed by cellular RNAi machinery. In recent research indicate that cellular microRNA can target the genetic material of invading viruses. Cellular microRNA can be used in the virus life cycle; either to up regulate or down regulate viral gene expression Computational tools use in miRNA target prediction has been changing drastically in recent years. Many of the methods have been made available on the web and can be used by experimental researcher and scientist without expert knowledge of bioinformatics. With the development and ease of use of genomic technologies and computational tools in the field of microRNA biology has superior tremendously over the previous decade. This review attempts to give an overview over the genome wide approaches that have allow for the discovery of new miRNAs and development of new miRNA target prediction tools and databases.
Abstract: Modeling and simulation of biochemical reactions is of great interest in the context of system biology. The central dogma of this re-emerging area states that it is system dynamics and organizing principles of complex biological phenomena that give rise to functioning and function of cells. Cell functions, such as growth, division, differentiation and apoptosis are temporal processes, that can be understood if they are treated as dynamic systems. System biology focuses on an understanding of functional activity from a system-wide perspective and, consequently, it is defined by two hey questions: (i) how do the components within a cell interact, so as to bring about its structure and functioning? (ii) How do cells interact, so as to develop and maintain higher levels of organization and functions? In recent years, wet-lab biologists embraced mathematical modeling and simulation as two essential means toward answering the above questions. The credo of dynamics system theory is that the behavior of a biological system is given by the temporal evolution of its state. Our understanding of the time behavior of a biological system can be measured by the extent to which a simulation mimics the real behavior of that system. Deviations of a simulation indicate either limitations or errors in our knowledge. The aim of this paper is to summarize and review the main conceptual frameworks in which models of biochemical networks can be developed. In particular, we review the stochastic molecular modelling approaches, by reporting the principal conceptualizations suggested by A. A. Markov, P. Langevin, A. Fokker, M. Planck, D. T. Gillespie, N. G. van Kampfen, and recently by D. Wilkinson, O. Wolkenhauer, P. S. Jöberg and by the author.
Abstract: The inhibition effect of brazilin to human bladder
tumor cell line T24 in vitro and in vivo was studied. The results of the
in vitro experiments showed that brazilin has strong inhibition activity
on the target cells. The inhibition ratio of 100 μg/mL brazilin and 100
μg/mL mitomycin to the target cells was 90.90 % and 63.24 %
respectively, which showed that brazilin has higher inhibition activity
than mitomycin under the same concentration. Brazilin could induce
cell apoptosis in T24 cells. Significant antitumor activity of brazilin
was also showed in the animals experiments. The life extention rate of
200 mg/mL, 300 mg/kg, and 400 mg/kg brazilin intraperitoneally
injected into Balb/c-nu-nu nude mice that with human bladder cancer
were 51.50 %, 56.90 %, and 58.42 %（P
Abstract: Breast cancer is the most common malignancy in the
world among women. Many therapies have been designed to treat
this disease. Mamectomy, chemotherapy and radiotherapy are still
the main therapies of breast cancer. However, the results were
unsatisfactory and still far from the ideal treatment.
PM 701is a natural product, has anticancer activity. The bioactive
fraction PMF and subfraction PMFK had been isolated from PM701.
PM 701 and its fractions were proved to have a cytotoxic properties
against different cancer cell lines. This article is directed for the
further examination of lyophilized PM701 and its active fractions on
the growth of breast cancer cells (MCF-7). PM 701, PMF or PMFK
were adding to the cultural medium, where MCF-7 is incubated.
PM 701, PMF or PMFK were able to inhibit significantly the
proliferation of MCF-7 cells, Moreover these new agents were
proved to induce apoptosis of the breast cancer cells; through its
direct effect on the nuclei.
Abstract: Ethanol is generally used as a therapeutic reagent against Hepatocellular carcinoma (HCC or hepatoma) worldwide, as it can induce Hepatocellular carcinoma cell apoptosis at low concentration through a multifactorial process regulated by several unknown proteins. This paper provides a simple and available proteomic strategy for exploring differentially expressed proteins in the apoptotic pathway. The appropriate concentrations of ethanol required to induce HepG2 cell apoptosis were first assessed by MTT assay, Gisma and fluorescence staining. Next, the central proteins involved in the apoptosis pathway processs were determined using 2D-PAGE, SDS-PAGE, and bio-software analysis. Finally the downregulation of two proteins, AFP and survivin, were determined by immunocytochemistry and reverse transcriptase PCR (RT-PCR) technology. The simple, useful method demonstrated here provides a new approach to proteomic analysis in key bio-regulating process including proliferation, differentiation, apoptosis, immunity and metastasis.
Abstract: Newcastle Disease Virus (NDV), an avian
paramyxovirus, is a highly contagious, generalised virus disease of
domestic poultry and wild birds characterized by gastro-intestinal,
respiratory and nervous signs. In this study, it was shown that NDV
strain AF2240 and V4-UPM are cytolytic to Human Promyelocytic
Leukemia, HL60 and Human T-lymphoblastic Leukemia, CEM-SS
cells. Results from MTT cytolytic assay showed that CD50 for NDV
AF2240 against HL60 was 130 HAU and NDV V4-UPM against
HL60 and CEM-SS were 110.6 and 150.9 HAU respectively.
Besides, both strains were found to inhibit the proliferation of cells in
a dose dependent manner. The mode of cell death either by apoptosis
or necrosis was further analyzed using acridine orange and propidium
iodide (AO/PI) staining. Our results showed that both NDV strains
induced primarily apoptosis in treated cells at CD50 concentration. In
conclusion, both NDV strains caused cytolytic effects primarily via
apoptosis in leukemia cells.
Abstract: The p53 tumor suppressor gene plays two important
roles in genomic stability: blocking cell proliferation after DNA
damage until it has been repaired, and starting apoptosis if the
damage is too critical. Codon 72 exon4 polymorphism (Arg72Pro) of
the P53 gene has been implicated in cancer risk. Various studies have
been done to investigate the status of p53 at codon 72 for arginine
(Arg) and proline (Pro) alleles in different populations and also the
association of this codon 72 polymorphism with various tumors. Our
objective was to investigate the possible association between P53
Arg72Pro polymorphism and susceptibility to colorectal cancer
among Isfahan and Chaharmahal Va Bakhtiari (a part of south west
of Iran) population. We investigated the status of p53 at codon 72 for
Arg/Arg, Arg/Pro and Pro/Pro allele polymorphisms in blood
samples from 145 colorectal cancer patients and 140 controls by
Nested-PCR of p53 exon 4 and digestion with BstUI restriction
enzyme and the DNA fragments were then resolved by
electrophoresis in 2% agarose gel. The Pro allele was 279 bp, while
the Arg allele was restricted into two fragments of 160 and 119 bp.
Among the 145 colorectal cancer cases 49 cases (33.79%) were
homozygous for the Arg72 allele (Arg/Arg), 18 cases (12.41%) were
homozygous for the Pro72 allele (Pro/Pro) and 78 cases (53.8%)
found in heterozygous (Arg/Pro).
In conclusion, it can be said that p53Arg/Arg genotype may be
correlated with possible increased risk of this kind of cancers in south
west of Iran.