Iranian Biomedical Journal
Volume:21 Issue: 3, May 2017

onsidering the high prevalence of severe organ failures due to the cancer, congenital anomaly, or trauma, and the consequent needs for tissue transplantation, deficiencies in tissues and organs are a huge challenge for regenerative medicine at the moment. More than 40 years have passed since the term ‘tissue engineering’ was created as a new therapeutic means, which may overcome the drawbacks involved in the current artificial tissue or organ transplantation. Nevertheless, application of regenerated tissues is still restricted mainly owing to the cost, poor biocompatibility, low bio-functionality, as well as immune rejection. Researchers have come a long way to make safer neotissues from cells with the support of new biomaterials, recombinant proteins, and the lower dose of growth factors for medical research or even clinical trials, but some critical problems should still be resolved for the use in human patients. Thus, these issues have lead to the emergence of a new concept that focuses on looking for an alternative approach to reconstruct tissue and organ using natural, safer and cost effective methods.
A major challenge in tissue engineering and cell culture is the use of serum, animal (Xeno) products, and recombinant proteins in the media or extracellular matrix, which are rather expensive, ethically questioned or problematic for researchers to study the mechanisms of a specific biological cascade. Attempts to imitate physiology of the human organs in the laboratory are getting closer to capturing their intricacies, which is needed for clinical applications. Therefore, to try to tackle the aforementioned problems, it is desirable to exploit natural compounds instead of synthetic materials as an alternative way to assemble functional constructs that restore, maintain, or improve damaged tissues or even whole organs.
Natural products, including plant derivatives and marine compounds, have widely demonstrated their worth as a cost-effective source of molecules and functional bio-composites with therapeutic potentials over thousands of years. In recent years, rapid advances in nanotechnology in addition to the extraction of the newly discovered natural small molecules opened an arena to produce functional human organs in sufficient structure and size at low cost for clinical applications.

The culture media optimization is an inevitable part of upstream process development in therapeutic monoclonal antibodies (mAbs) production. The quality by design (QbD) approach defines the assured quality of the final product through the development stage. An important step in QbD is determination of the main quality attributes. During the media optimization, some of the main quality attributes such as glycosylation pattern, charge variants, aggregates, and low-molecular-weight species, could be significantly altered. Here, we provide an overview of how cell culture medium components affects the main quality attributes of the mAbs. Knowing the relationship between the culture media components and the main quality attributes could be successfully utilized for a rational optimization of mammalian cell culture media for industrial mAbs production.

Epidemiological studies have probed the correlation between telomere length and the risk of lung cancer, but their findings are inconsistent in this regard. The present meta-analysis study has been carried out to demonstrate the association between relative telomere length in peripheral blood leukocytes and the risk of lung cancer using an established Q-PCR technique.
A systematic search was carried out using PubMed, EMBASE, and ISI before 2015. A total of 2925 cases of lung cancer and 2931 controls from 9 studies were employed to probe the relationship between lung cancer and telomere length .ORs were used at 95% CI. Random-effects models were used to investigate this relationship based on the heterogeneity test. Heterogeneity among studies was analyzed employing subgroup analysis based on type studies and the year of publication.
Random-effects meta-analysis revealed that patients with lung cancer were expected to have shorter telomere length than the control (1.13, 95% CI: 0.82-1.81, P=0.46). The summary of the pooled ORs of telomere length in adenocarcinoma lung cancer patients was 1 (95%CI=0.68-1.47, I2=93%) compared to patients with squamous cell lung cancer, which was 1.78 (95% CI=1.25-2.53, I2=3.9%). The meta-regression revealed that the effect of telomere length shortening, decreased and increased with the year of publication and the age of risks to lung cancer, was clearly related to short telomeres lengths.
Lung cancer risks clearly related with short telomeres lengths. In patients with breathing problems, lung cancer risk can be predicted by telomere length adjustment with age, sex, and smoking.

Culture media enrichment through the addition of protein hydrolysates is beneficial for achieving higher protein expression.
In this study, designing the optimum mixture of four soy and casein-derived hydrolysates was successfully performed by design of experiment and specific productivity increased in all predicted combinations. Protein profile of recombinant CHO (rCHO) cells producing tissue plasminogen activator in a serum-free medium (SFM) supplemented with designed hydrolysate additives was compared to that of rCHO cells cultivated in SFM.
Identification of differentially expressed proteins using two-dimensional gel electrophoresis coupled with MALDI-TOF/TOF revealed the role of energy metabolism related proteins and importance of prevention of oxidative stress by this special media enrichment strategy. Up-regulation of mitochondrial enzymes, pyruvate dehydrogenase E1 and Peroxiredoxin-III, as well as other proteins involved in metabolic pathways, and uridine monophosphate/cytidine monophosphate kinase indicated higher metabolic activity. Furthermore, along with antioxidant effect of peptones, proteins with antioxidant function such as ferritin and peroxiredoxin-III were up-regulated.
Understanding molecular mechanisms involved in enhancement of protein expression can provide new approaches for efficiently engineering rCHO cell. These results support the competence of proteomics studies in finding new insights to biochemical pathways for a knowledge-based optimization of media compositions.

Gap junctions (GJs) provide direct intercellular communications that are formed by hexameric protein subunits, called connexin (Cx). The role of Cxs in epileptogenesis has not received sufficient attention. Hippocampus with critical function in epileptogenesis has a wide network of GJs. We examined the protein expression levels of hippocampal Cx36 (the prominent Cx present between GABAergic interneurons) and Cx43 (the main Cx expressed by astrocytes) during epileptogenesis in the pilocarpine model of epilepsy.
Male Wistar rats received scopolamine (1 mg/kg, s.c.). Pilocarpine (380 mg/kg, i.p.) was administered 30 min thereafter to induce status epilepticus (SE). SE was stopped 2 h later by diazepam (10 mg/kg, i.p.). Cx36 and Cx43 protein expression was assessed by Western blot analysis in the hippocampus of SE-experienced rats, after injection of diazepam (F0 subgroup), after acquisition of focal seizures (F3 subgroup), and after development of generalized seizures (F5 subgroup). The control subgroups, C0, C3, and C5, were aged-matched rats, which received saline (1 ml/kg, i.p.) instead of pilocarpine. Injection of scopolamine and diazepam, and dissection of hippocampi were carried out at the same time interval as the test subgroups.
SE emerged in 67.1% of pilocarpine-treated animals. Focal and generalized seizures developed 3.8±0.4 and 7.0±0.5 days after SE, respectively. Cx36 protein abundance was not significantly different between test and control groups in the three time points. However, Cx43 protein level showed 40% increase in F3 subgroup (P Hippocampal Cx43 is overexpressed in pilocarpine model of epileptogenesis after acquisition of focal seizures.

Despite the emerging evidence on beneficial effects of probiotics on the cardiovascular system, their impact on the management of ischemic heart diseases and its possible mechanism have not been elucidated.
Four viable probiotics bacterial strains, including Bifidobacterium breve, Lactobacillus casei, Lactobacillus bulgaricus and Lactobacillus acidophilus, at the concentrations of 2×106 colony-forming units/ml were orally administered to the rats daily for 14 days before the induction of infarct-like myocardial injury using isoproterenol. Subsequently, 24 h after myocardial injury, the right carotid artery and the left ventricle were catheterized for recording blood pressure and cardiac parameters. At the end of the experiment, the heart was removed for the evaluation of histopathological and biochemical parameters, as well as tumor necrosis factor-alpha (TNF-α) assay.
The induction of acute myocardial injury resulted in significant (P≤0.01) left ventricular (LV) dysfunction, as shown by an increase in LV end-diastolic pressure and a decrease in LV dp/dt max, LV dp/dt min, LV systolic pressure, and blood pressure, as compared with normal rats. Pretreatment with viable probiotics significantly reduced lipid peroxidation and TNF-α level and improved cardiac function (P This study shows that viable probiotics have a cardioprotective effect on infarct-like myocardial injury through suppressing TNF-α and oxidative stress damage in a rat model. Probiotic supplements may be used as a new option for prophylaxis in patients at the risk of ischemic heart disease in future.

Phototherapy is believed to be a safe method for the management of hyperbilirubinemia. However, there are some controversial issues regarding the genotoxic effects of phototherapy on DNA. The aim of this study was to investigate morphologically both phototherapy-induced DNA double-strand breaks (DSBs) and apoptosis in lymphocytes derived from jaundiced and non-jaundiced neonates.
Newborns were divided into three groups, including phototherapy-treated (PT, n=30) jaundiced newborns with total serum bilirubin (TSB) levels >15 mg/dl, non-treated jaundiced newborns (C, n=27), as positive, as well as healthy negative (C-, n=30) controls with TSB levels ranging from 10 and 15 mg/dl and less than 5 mg/dl, respectively. Lymphocytes were isolated from whole blood samples by Ficoll-isopaque density gradient centrifugation and then assessed for DNA damage and apoptosis before and 24 hours after incubation at 37°C in 5% CO2 using the neutral comet assay.
DSB levels were significantly much higher in the PT group compared to the controls before incubation but decreased remarkably after the incubation period. As expected, no statistical differences were found between the two control groups before and after incubations. The frequency of apoptotic cells showed no significant differences among all the three groups before incubation; however, it was significantly increased in the PT group after incubation.
It seems that phototherapy in jaundiced infants is able not only to induce apoptosis in newborn lymphocytes but also to affect indirectly DNA integrity.

Scorpion venom is a source of bioactive peptides, and some antimicrobial peptides (AMPs) have been found in the venom gland of scorpions. Therefore, the discovery of new anti-infective agents is an essential need to overcome the problem of antibiotic resistance of clinical isolates. Here, we describe three new cationic AMPs, including meuVAP-6, meuAP-18-1, and meuPep34 from the venom gland of the Iranian scorpion, Mesobuthus eupeus.
The cDNA sequences encoding all the three peptides were obtained from the cDNA library of scorpion venom gland and were deposited in the GenBank database.
MeuVAP-6 and meuAP-18-1 are non-disulphide-bridged antimicrobial peptides, while meuPep34 is a cysteine-rich defensin-like peptide.
All three identified AMPs are rich in arginine and tryptophan. The overall results from the length, net charge, and hydrophobicity index suggested that meuPep34 could be the most active AMPs with the potential ability of biofilm inhibition. The data from molecular characterization of identified AMPs can provide a platform for further investigations in the drug design.

There is a controversy about the relation between anti-hepatitis B (anti-HBs) antibody level and obesity. We designed this study to compare the vaccine efficacy in obese/overweight and non-obese cases.
In this cross-sectional study, 242 obese/overweight and 85 non-obese individuals were participated. Cases were selected from a referral clinic for obesity and a referral hepatology clinic, both in Tehran, Iran.
Obese cases had lower percentage of liver diseases (66.9% vs. 100%, P The level of anti-HBs surface antigen antibody’s titer in obese cases without liver disease is lower than control group. Therefore, a suitable strategy is needed to overcome this problem, which can be the use of longer needles for vaccination.