A review on microfluidics applications in biotechnology
Volume 16, Issue 4, Autumn 2025, Pages 1-14
https://doi.org/10.48311/biot.2025.103407.0
Mohadeseh Khalili, Farzaneh Shayganfar, Asieh sadat Kazemi
Abstract Microfluidic technology, known as the study and manipulation of fluid flow in channels with micrometer-scale dimensions, is one of the most important achievements in recent decades in the field of miniaturization technologies. By integrating knowledge from engineering, physics, chemistry, and biology, this technology enables the precise control and analysis of very small volumes of liquids, where fluid behavior at this scale differs significantly from the macro scale. Key features of microfluidics include precise control of physical parameters, reduced consumption of samples and reagents, faster experimentation, and the ability to perform multiple processes simultaneously. These advantages have led to the development of devices known as “lab-on-a-chip,” which can carry out complex biological processes in small, portable formats. In recent years, this technology has gained a prominent position in various fields of biotechnology and medicine. Its notable applications include rapid disease diagnosis, genetic analysis, drug screening, targeted drug delivery, and modeling of human tissues and organs. Moreover, advances in polymeric chips and paper-based microfluidics have further expanded the potential applications of this technology. The aim of this article is to provide a comprehensive review of microfluidic technology applications in biotechnology and to examine the most significant advancements, challenges, and future perspectives in three areas: pharmaceuticals, diagnostics, and bioengineering.
Investigations on various methods for cryopreservation of Echium amoenum Seeds
Volume 16, Issue 4, Autumn 2025, Pages 109-117
https://doi.org/10.48311/biot.2025.103383.0
Leila Ghaffarzadeh
Abstract Echium amoenum is a member of the Boraginaceae family, which has very valuable medicinal properties that are highly regarded in traditional Iranian medicine. Because different plant species Echium inappropriate harvesting of natural areas by humans, and the growing threat of biotic and abiotic stresses following the work resulted in reduced genetic diversity of a species is, a species of genetically keep reserves Curb upper's. Using seed cryopreservation, as one of the Ex situ plant germplasm conservation method we can store seed for long-term, with much lower expenses and without losing seed viability. In order to preserve E. amoenum seed under -196 ºC condition, three pre cryopreservation treatments, PVS2 solution, Desiccation and Glycerol were applied. The treated seeds were transferred into Liquid Nitrogen (LN) and stored for 1 week. In this study the effect of cryopreservation on germination and growth indices (germination percent, germination rate of plant species (E. amoenum) in storage conditions of cryopreservation (-196ºC) were evaluated for 1 week. Comparing treatments, significant differences were observed on germination percent and germination rate. The best treatment was desiccation. The results showed that, the long-term preservation of the species, seed in -196 ºC is possible.
Cloning, Recombinant Expression and Evaluation of Biochemical Properties of Glutaminase from native strain Alteribacillus bidgolensis
Volume 16, Issue 3, Summer 2025, Pages 42-56
https://doi.org/10.48311/biot.2025.27531
Saba Moafi, Sajjad Sarikhan, Abdolhamid Angaji, Hossein Ghafouri
Abstract L-glutaminases (L-glutamine amidohydrolase, 3.5.1.2) belong to the superfamily of serine-dependent β-lactamases and penicillin-binding proteins. L-glutaminases have received much attention in the last few decades due to their catalytic ability to deaminate glutamine to glutamic acid and ammonia; a property that has made them valuable in different industrial applications, especially in medicine. Research on glutaminase has progressed during the last four decades, though slowly in comparison to other industrially important enzymes. The relatively high cost of glutaminase is one of the major drawbacks hindering its industrial applications. The current production levels of glutaminase are also insufficient for the required clinical trials to facilitate its medical uses and for other applications.The purpose of this study is the solubilized recombinant expression and functional assay of L-glutaminase from Alteribacillus bidgolensis (P4BT) in an E. coli BL21 (DE3) expression system. In this study, the L-glutaminase gene was successfully cloned with the pET30a expression vector in the E. coli BL21 (DE3) expression system. Solubilized expression was achieved with the aid of the pG-KJE8 vector, which contains molecular chaperones. Ultimately, the specific activity of the purified and dialyzed enzyme was assessed at 40°C and pH 8, yielding an enzymatic activity of 0.53 ± 0.01 U/mg at a substrate concentration of 8 mM. The Km value for L-glutaminase was calculated at 3.10 mM, with a Vmax of 0.62 U/mg.
Theoretical Design via Umbrella Sampling and Experimental Investigation of a New Mutation in Cap37 to Increase its Antibacterial Property
Volume 16, Issue 2, Spring 2025, Pages 30-41
Mehri Hedayati, Karim mahnam, Behnaz Saffar
Abstract Abstract
The increase in antibacterial resistance due to the high consumption of antibiotics is a looming crisis for humanity. Natural antibacterial compounds, such as cationic antibacterial peptides, hold a significant position, as the likelihood of developing resistance against them is low. CAP37, or AZU1, is a protein derived from the granules of human neutrophils and functions as a natural antibiotic. The residues 20-44 of CAP37 exhibit antibacterial activity. In this study, two mutations were designed in the native CAP37 peptide to enhance its antibacterial activity. Molecular dynamics simulations of the peptides in water were conducted for 50 ns, along with umbrella sampling MD simulations to obtain reliable potential of mean force (PMF) profiles for each peptide's passage through lipid A, a component of the bilayer membrane. The results indicated that the peptide containing the SWRW sequence exhibited lower aggregation properties in water and a greater tendency to traverse the lipid A bilayer membrane compared to the native (SQRS) or WWRS sequences. Therefore, it can be concluded that CAP37 with the SWRW sequence has enhanced antimicrobial activity. To validate the theoretical findings, both the natural and SWRW mutant peptides were synthesized. The minimum inhibitory concentration (MIC) test conducted on various Gram-negative and Gram-positive bacteria, including Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus subtilis, demonstrated that the mutated peptide exhibited antibacterial activity, thereby confirming the theoretical results.
Cerasome-Antibody: A smart Nanocarrier toward Diagnostic and Delivery Applications
Volume 15, Issue 4, Autumn 2024, Pages 52-66
Maryam Vesal, Zahra Vaezi, Abdollah allahverdi, Hossein Naderi-Manesh
Abstract In recent years, targeted drug delivery systems have emerged as a promising approach to increase the efficacy and minimize side effects of therapeutic agents. Cerasomes are a special type of liposomes with covalent siloxane networks on the surface that provide exceptional morphological stability while retaining all the beneficial properties of liposomes. Cerosomes provide a unique platform for drug encapsulation and delivery due to their biocompatibility, stability, controllable release, and long-term storage. In this research, an attempt has been made to engineer the surface of cerosomes to increase the selectivity and efficiency of drug delivery. In such a way that the Herceptin antibody is placed on the surface of the serosa and allows the precise targeting of HER2+ cells. Then, the physicochemical characteristics of antibody-functionalized cerosomes, including size and surface charge 229±15.6 nm and 13.5±1.2 mV were respectively obtained. The results of IR and fluorescence spectrum showed that the antibody was successfully attached to the surface of cerasome with a binding efficiency of 64%. These results prove the basic mechanisms governing the synthesis of immunocerasomes and provide a valuable approach for future developments in targeted drug delivery systems.
The computational study of the tautomerization of Carmustine drug in the biological system: DFT approach
Volume 15, Issue 4, Autumn 2024, Pages 91-99
Mahnoush Momeni Landi, sayed ali ahmadi, Mohammad Reza Akhgar, Dadkhoda Ghazanfari
Abstract Tautomers are isomers of a molecule that exist in solution or in a cell. They are interchangeable forms because chemical bonds are rearranged many times spontaneously. This is different from chirality, where molecules are mirror images (or enantiomers) of each other. DFT method was carried out to study the tautomerization of the mechanism of carmustine as an anti-cancer drug. In the carmustine structure, two conformational tautomers were predicted and both two tautomer structures were demonstrated for considering the role of changing atoms in the conformation of carmustine. Relative energies obtained at the B3LYP/6-311G++ (d,p) , Aug-cc-pVDZ and 6-311++g(2d,2p) basis sets. The highest occupied molecular orbital (HOMO), The lowest unoccupied orbital (LUMO), and bandgap energy of structures were calculated. Electronics parameters were obtained. electrophilicity. Electronegativity, softness, and hardness for determining the reactivity of compounds in biological media. have been studied. According to the data, the structure of carmustine and two tautomer conformations are stable but T1 is more stable than the other one.
Metformin and p-coumaric acid alter the expression of some EMT genes in gastric cancer cell line AGS
Volume 14, Issue 4, Summer 2023, Pages 1-10
Youssof Sefidi-Heris, Iraj Saadat
Abstract Gastric cancer is one of the most common cancers in the world. Its treatments are costly and can cause severe side effects. As a result, treatments with natural compounds, well-established therapeutics, or combinations of both groups may be effective alternatives. p-Coumaric acid (pCA) and metformin (Met) are among such anticancer treatments. Epithelial-mesenchymal transition (EMT) is a multi-purpose process that plays a critical role in gastric cancer. This process involves a complex network of biological markers participating in gastric cancer initiation and metastasis. Subsequently, the agents downregulating the expression of EMT markers may be potential anti-gastric cancer therapeutics. Because the effects of pCA, Met, and their combination on the expression of EMT markers ZEB1, Snail2, Vimentin, and VEGFA have not been inspected, the present study aimed at assessing these effects. MTT assay determined the cytotoxicity of pCA and Met on the AGS cells for 48 hours. Real-time PCR was used to evaluate the changes in the expression levels of these EMT genes after 48 hours. A combination of pCA and Met downregulated the expression of ZEB1 and Vimentin genes at low, non-cytotoxic concentrations. Therefore, they may be potential candidates for further investigations in fighting against gastric cancer.
Investigation of the efficacy of doxorubicin combined with increased expression of caspase 9 on SH-SY5Y neuroblastoma cell line
Volume 14, Issue 4, Summer 2023, Pages 11-23
Seyed-Hossein Beheshti Shoushtari, Farangis Ataei, Saman Hosseinkhani
Abstract SH-SY5Y is a neuroblastoma cell line which used as a cancer and neurodegenerative disorders model and its neuro-experimental studies. The different diseases cause by a defect in apoptosis pathway. Disruption of apoptotic proteins has an effect on the treatment process and response to drugs. In nerve cells, due to the high expression of apoptosis inhibitory proteins, the efficacy of drugs is low. Combination therapy is one of the developing treatment methods. The aim of this research is to evaluate the effectiveness of doxorubicin drug on apoptosis in SH-SY5Y cells under the conditions of high expression of caspase9. Caspase9 is a key enzyme in intrinsic apoptosis. First, cell viability was obtained through MTT assay under the different drug concentrations. Then, caspase9 gene was transfected in cells and affected by the concentration lower than IC50 of drug, and cell energy level and cell death were checked by different methods. ATP assay showed that the expression of caspase9 with drug lead to ATP decreases. Caspase3/7 activity indicated an increase in cell death by drug and caspase. Propidium staining to hoechst showed that the expression of caspase9 in combination with doxorubicin induce more death. To ensure the expression levels of protein that induces cell death, the amount of caspase3 protein was checked by western blotting, which showed a significant increase in combination of caspase9 and drug. Our findings showed that the induction of caspase9 expression intensifies the effect of drug and the combined treatment may be effective on the responsiveness of neuronal diseases.
Induction of permeability in the blood-brain barrier using focused ultrasound to increase the effect of neuroprotective agents in Parkinson's disease
Volume 14, Issue 2, Spring 2023, Pages 94-113
Narges Nasrollahi Boroujeni, Farhang Ali Akbari, Dina Morshedi
Abstract Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and the prevalence of it has increased worldwide. PD causes severe damage to loss of midbrain dopaminergic neurons (DN) at substantia nigra which involves in the movement control. The synaptic terminals of DNs are destroyed in the posterior putamen. PD is also characterized by accumulation of misfolded and amyloid α-synuclein into proteinous inclusions named Lewy bodies. So far there is no effective treatment for PD and approved medications for PD can only slow down clinical progression, control motor and non-motor symptoms. Currently, the approved medications just induce the release of dopamine and prevent the release of acetylcholine from nerve terminals of caudate cholinergic interneurons and it is necessary to provide more effective treatment methods in the early stages of the disease. Significant progress has been achieved in development of drugs that can reduce neuronal cell death and lead up to neuroprotection, however targeting delivery of drugs to improve the pharmaceutical effects of drugs is remained as a challenge. Therefore, there is a pressing demand to find practical strategies for delivering these pharmaceuticals in vivo through the BBB without disrupting the brain's functions. In this regard, Focused ultrasound (FUS) technology eliminates the need for brain surgery and temporarily opens the blood-brain barrier to allow drugs to pass through. In this review, the application of FUS as a new drug delivery application in the PD models and the potential clinical application of neuroprotective agents are provided briefly.
Comparison of titer and neutralization of antibody, SARS-CoV-2 spike protein expressed in eukaryotic and prokaryotic cells
Volume 14, Issue 1, Winter 2023, Pages 130-141
sahar karimi, Shahram Nazarian, fattah Sotoodehnejadnematalahi, Roohollah Dorostkar, Jafar Amani
Abstract Given the global epidemic of COVID-19, it is important to design a vaccine for prevention. The virus belongs to the beta-coronavirus family and forms appendages on the surface of the glycoprotein spike virus membrane. Studies on SARS-CoV-1 and related MERS-CoV vaccines have shown that the spike protein on the virus surface is a suitable target for the vaccine. In this experimental study, we compare the recombinant fragment of spike protein (rfsp) expressed in the eukaryotic host CHO-K1 cell and prokaryotic E. coli in terms of immunogenicity, neutralizing activity, and epitopes recognition Similar to the virus strain and the ability to bind to the serum of improved patients, in two types of alpha and delta variants. The results showed that both rfSP proteins are a potential new antigen candidate for the development of the Covid 19 vaccine, but the CHO cell maintains the biological activity of the protein by performing post-translational modification processes such as glycolysis. This increases the present likelihood of developing virus-like epitopes and increases the titer of rfsp-specific antibodies in the serum of immunized mice. Therefore, priority is given to rfsp expressed in CHO cells to evaluate vaccine efficacy.
Evaluation of Interactions between Amid/Acid Hydrogel with Bicalotamide Anticancer Drug Using Molecular Dynamics
Volume 13, Issue 4, Winter 2023, Pages 1-17
Rahim Ghadari, Siamak Ahmadzadeh
Abstract Designing new drug delivery systems is important; therefore, in the present study the interaction between an anti-cancer drug, bicalutamide, and an amide/acid hydrogel was studied. Analyzing was done by using docking and molecular dynamics simulation methods. Molecular dynamics simulations were performed at 37 and 42 °C. The results showed that the binding free energies of the drug to the hydrogel system at two temperatures were similar, and altering the temperature did not affect the stability of the system. The van der Waals interaction is the most crucial interaction between the drug and the hydrogel, which depends on the distance between the drug and hydrogel. Intra- and intermolecular hydrogen bonds and van der Waals interactions, are the major factors in the stability of the hydrogel system. Due to the stability of the studied system, it can be used as a drug carrier.
Elicitors and precursors, an effective strategy for increasing betulin an anticancer agent in Betula litwinowii callus cultures
Volume 13, Issue 3, Winter 2023, Pages 30-39
Nastaran Mehrirad, vahide Payamnoor, Jamile Nazari
Abstract Betulin is a pentacyclic lupane-type triterpene, mainly obtained from Betula species plants with a variety of biological actions such as anti-HIV and anticancer properties. This study aimed to enhance the production of betulin in cultures of Betula litwinowii calli under the influence of concentrations and duration time of elicitors and precursors. Collected leaves from Sangdeh habitat in summer, were cultured in WPM medium containing 2,4-D and BAP hormones. Four month calli were sub-cultured in medium containing elicitors such as salicylic acid, chlorocholine chloride and cobalt chloride and precursors such as sucrose, vitamin and glucose. . Calli were harvested from new culture media after two, three and four weeks and their wet and dry weights were calculated. Data analysis was performed based on two-factor factorial experiment (the first factor, elicitors and precursors each in four levels and the second factor, time with three levels) in a completely randomized design with three replications with SPSS software. Duncan's multiple range test were performed to compare the mean (p≤0.01). The results showed that two week elicitation with chlorocholine chloride (1.5 mg/l for one week) was the best with a more than 3-fold increasing in betulin induction compared to the control treatment (0.068 mg / g). The use of vitamin precursor (ten-fold the normal amount in WPM culture medium) for three weeks, causes the highest increase in betulin induction compared to the control (0.1 mg / g, respectively). In general, in the present study, this treatment is introduced as the best.
A look at the Factors Affecting the Commercialization of Products in Iranian Medical Biotechnology Accelerators
Volume 13, Issue 2, Winter 2023, Pages 178-201
soode mirmohamadi, MORTEZA SOLTANI, fereidoun mahboudi, meysam shahbazi
Abstract This study investigates the factors affecting the commercialization of products in medical biotechnology accelerators, it also demonstrates the priority of these factors. The research is applied and descriptive survey. It has been done in two phases, qualitative and quantitative. Based on the general purpose of this study, to provide a framework for the commercialization of products in medical biotechnology accelerators, we interviewed with informed experts. 62 sub-codes were obtained as effective factors in the commercialization of products in medical biotechnology accelerators, which were classified into 5 main dimensions including individual, organizational, industry and competition, institutional and product. These dimensions are presented as a framework. In the quantitative phase, the main dimensions as well as the sub-themes were ranked in the main dimension. Finally, the priority of the main dimensions was as follows: 1. Individual (personality, behavioral and mental characteristics of the mentor and manager) 2. Industry and competition (interaction with pharmaceutical companies as customers, investors, etc.) 3. Organizational (experience of startup teams, codified strategy, R&D, etc.) 4. Product (value added and high-tech) 5. Institutional (government is pragmatic to the country's slogans, interaction with government managers, etc.).
A Comparison of Curcumin and Nanocurcumin Effect on the expression of the vascular endothelial growth factor (VEGF-A) in HeLa cell line
Volume 13, Issue 1, Winter 2022, Pages 107-119
Rezvaneh Vahedian Sadeghi, masoud Parsania, Majid Sadeghizadeh, Setareh Haghighat, Seyedeh Sahar Mortazavi Farsani
Abstract Abstract
Introduction: Cervical cancer is the fourth most common cancer among women. In recent years, attention has increased to natural products such as curcumin with anti-cancer potential as a therapeutic supplement. However, due to its poor solubility, its clinical use is limited. In this regard, in this study, to improve clinical parameters, the effects of nanocurcumin on the angiogenesis inhibition of cervical cancer were investigated and compared with free curcumin.
Materials and Methods: MTT method was used to evaluate the proliferation of the HeLa cell line with free curcumin and nanocurcumin at different doses and time intervals and the rate of apoptosis was assessed by flow cytometry. Then, the expression of the vascular endothelial growth factor (VEGF-A) gene in HeLa cells was measured by Real-Time PCR and Western blotting, respectively.
Results: According to IC50 for 48 hours in the HeLa cell line, which was 15 μM/ml and 50 μM/ml for nanocurcumin and free curcumin, respectively, the nanocurcumin showed a greater lethal effect. VEGF-A gene expression (p <0.0001) and protein level (p <0.01) were significantly lower following nano-curcumin treatment than free curcumin.
Conclusion: Nanocarrier increased the solubility and further inhibited the proliferation of cervical cancer HeLa cells and was three times more effective than curcumin in inhibiting angiogenesis at the same concentration. Therefore, nanocurcumin can be a good option for drug supplementation along with routine cervical cancer treatment.
Keywords: Cervical cancer, Nanocurcumin, HeLa cell, VEGF-A.
Design, Synthesis and Biological Evaluation of a Novel Sulfonamide Derivative as antiproliferative agents for Human Breast Cancer Cell line (MCF-7)
Volume 12, Issue 2, Winter 2022, Pages 91-102
Mohaddeseh Baravordeh, Hossein Ghafouri, Asadollah Mohammadi, Sevda Zarei
Abstract Aim: During the uncontrolled development of cells in the body, a subset of neoplasms or tumors is formed, the abnormal proliferation of these cells leads to the formation of a mass and eventually cancer. This mass can spread throughout the body. Thus, inhibiting the abnormal growth of cancer cells will have a significant effect on preventing the spread of cancerous tumors and improving the disease. Therefore, in the present study, a new sulfonamide derivative was designed and synthesized (HB20) and its anti-cancer effects on human breast cancer cell line (MCF-7) were investigated.
Materials and Methods: For the synthesis of a sulfonamide derivative (HB20), dcriptiazonium salt was first made using a sulfamethoxazole base compound and then combined with a pyrimidine coupling agent. Concentrations of a new synthetic compound (HB20) against Cells (MCF-7) were used. MTT assay was also performed to measure survival and cell proliferation.
Results: The synthesized compound structure was confirmed by spectral analysis, such as FT- IR, and NMR. Also, Survival in MCF-7 cells treated with a synthetic compound (HB20) was significantly reduced compared to the control group (untreated). HB20 inhibits the proliferation of MCF-7 cancer cells with an IC50 value of 75/23 μg/ml.
Conclusion: The new sulfonamide derivative (HB20) has the potential to inhibit proliferation and anti-cancer properties in the cell line (MCF-7).
open innovation system in Iran's biopharmaceutical industry
Volume 12, Issue 4, Autumn 2021, Pages 49-80
hadi siadati, Sepehr ghazinoory, mehdi fatemy
Abstract The biopharmaceutical industry in Iran is developing in parallel with the global trend. Given the risks and costs of research, development, production, and sales of these drugs, firms have moved toward open innovation models across different value chains in the last decade. However, the limited use of technological cooperation methods by the Iranian firms will trap the industry in genericization soon. Accordingly, the development of an open innovation system in the value chain of the Iranian biopharmaceutical industry provides the possibility of continuous development of the industry. In the present study, first, the technological capabilities of the firms in the Iranian biopharmaceutical industry were evaluated, and then some cases of technological cooperation in the industry were studied deeply. Accordingly, considering the "strategic" level of technological capability of firms and also the lessons learned from the multicase study of the experiences of the Iranian pharmaceutical firms, strategies including the completion of the value chain links, the use of export development tools, the supporting of the commercialization in universities and research institutes, the facilitation of technology integration and acquisition and finally the development of smart public financial support to develop are proposed for the development of open innovation system in the Iranian biopharmaceutical industry.
Bone morphogenetic proteins-2 and its medical applications
Volume 12, Issue 4, Autumn 2021, Pages 147-165
Zahra Shahsaman, Sadegh Hasannia
Abstract Bone morphogenetic proteins (BMPs) are a subfamily of multifunctional superfamily transforming growth factor-beta (TGF-β), thus they have a lot of similarity in biosynthesis, structure, signaling and biological function with other members of the superfamily. They are involved in growth and differentiation of embryo to maintenance of adult cells. Among this family member, BMP-2 is a valuable protein that acts in different processes such as spinal fusions, articular cartilage damage therapy, tumor inhibition, gingivitis and dental treatment. The high importance of this protein and its low production rate in body caused several researches in the field of producing recombinant BMP-2 in different hosts. Recombinant production of the protein in bacterial host caused the decrease in production costs and therefore led to the common use of BMP-2 in treatment of various diseases. To date, positive effects of intact BMP-2 and its derivative peptides, in order to osteoinduction in fracture treatment and jaw bone regeneration for dental implantation, were considerable. Considering high clinical significance of BMP-2, there is a necessity for more investigations in relation to this protein.
Synthesis and characterization of biocompatible chitosan/aminotetrazol nanoparticles as a novel nanocarrier for gene delivery
Volume 12, Issue 3, Summer 2021, Pages 123-136
Elaheh Mosaddegh, Masoud Torkzadeh-Mahani
Abstract This article has been attempting to present a novel and biocompatible nanocarrier based on chitosan biopolymer with high efficiency and low toxicity for gene delivery. At the first, 5-amino-1H-tetrazol reacted with (3-chloropropyl)trimethoxysilane and then, the obtained organosilane intermediate was used for functionalization of chitosan amino groups. The structure and chemical composition of the synthesized nanocarrier were fully characterized by FESEM, TEM, XRD, FTIR, Zeta potential and DLS analysis. At the fallowing, the MTT test was performed in order to investigation of the nanocarrier toxicity. Furthermore, Hek-293T cell line was used for investigation of the nanocarrier efficiency in gene transfection toward the cell. The loading capacity of plasmid was optimal at an N/P ratio of 3 with excellent protection of the plasmid. The results were shown that the novel nanocarrier is high efficient and has high potential to gene transfection and protection in addition of nontoxicity, biodegradability and cost effectively.
Extraction and identification of Gallic acid and Protocatechuic acid from fruit juices of Rhus coriria and preparation silyl derivatives of these compounds to increase their lipophilic nature and drug's effectiveness
Volume 11, Issue 4, Autumn 2020, Pages 1-15
Abdolreza Abri, Saeed Hasankhani
Abstract Aims: The aim of this study was to extract, isolate, purify, identify and determine the percentage of two natural combinations of protocatechoic acid and gallic acid from Sumac with high efficiency. These compounds exhibit good antimicrobial, antiviral, antifungal, anti-diabetic, anti-insect and parasitic and antioxidant properties. Subsequently, to enhance the drug efficacy of these compounds, their silyl derivatives were prepared.
Materials & Methods: The Rhus coriria plant from the trees of the Naghadeh, from the trees of the Aras Baran and from the trees of the Shitaneh village was collected. They were dried in the shadow and grinding. After extraction, to identify two important compounds and their silyl derivatives, we use FT-IR, 1H-NMR, 13C-NMR, GC-Mass, DSC, XRD and HPLC methods.
Findings: According to experiments, it can be concluded that the sample of Iranian Sumac fruits in Arasbaran region has the highest amounts of gallic acid (2.99%) and protocatechoic acid (2.902%). We also conclude that the type of soil and the location of growth of a genus are quite influential in its active ingredients, taste, and color. By silylation of these compounds, the lipophilic properties increase sharply, that is, they pass easily through the cell membrane and increase their judgment effect.
Conclusion: In this research work, two high-efficiency natural compounds were extracted from the samples of Sumac. Subsequently, due to their medicinal properties, silyl derivatives were prepared and their structure identified by spectroscopic methods. In this way, the permeability of the cell membrane easily done and the pharmacological effect of greatly increased.
Production of a novel hyper-glycosylated human coagulation factor IX in HEK293 cells, using a Glyco-engineering Approach
Volume 11, Issue 3, Autumn 2020, Pages 50-58
ّFahimeh Ghasemi, Alireza Zomorodipour, Ali Asghar Karkhane
Abstract Hyper-glycosylation is an approach to introduce new N-glycosylation consensus sequence(s) (َAsn-Xxx-Ser/Thr three-peptide) into a protein primary amino acid sequences by site-directed mutagenesis which is followed by the attachment of a new glycan to the Asn residue located within the three-peptide sequence. Hyper-glycosylation has attracted lots of interest especially in the protein therapeutics industry. The attached glycan may improve the pharmacokinetic properties of the hyper-glycosylated priteins and increase their half-life in the bloodstream. In the current study, a new N-glycosylation site was introduced into N-terminal Gla domain of hFIX. Arg37 position of mature hFIX was targeted to be converted into Asn residue by site-directed mutagenesis using overlap extension PCR. Recombinant expression plasmids for native and mutant hFIX were constructed. The expression of the recombinant wild-type and mutant hFIX was analyzed in mammalian HEK293 cells using gradient SDS-PAGE and western blotting analysis. The results indicated in higher molecular weight for R37N mutant in compared with the native protein. The glycan attachment to R37N mutant was further confirmed by PNGase digestion and western blotting.
Structural Insight into the role of Inhibitor Peptide derived from Tumstatin-Integrin Complex in Inhibitory Mechanism: A Molecular Dynamics Simulations Study
Volume 11, Issue 2, Spring 2020, Pages 137-144
mohammad ghorbani, Majid Taghdir
Abstract Integrin inhibitors may change conformational and dynamical properties of integrin, but its molecular properties in this process is not clearly understood. Tumstatin is an anti-angiogenesis protein derived from collagen XVIII, but little is known about how tumstatin applies its antiangiogenic and antitumor effects. It has been reported that 18 amino acids fragment of tumstatin has anti-tumor activities similar to tumstatin. We used molecular docking and molecular dynamic simulations to describe inhibitor activity of peptide in molecular level. We described the binding of this peptide to Hybrid/EGF-4 interface and that these interactions might contribute to improved hydrophobic interactions at these regions and also fixed the mobile domains of integrin. In the complex, we recognized a novel binding site on integrin for integrin inhibitors that may have critical role in integrin inhibition. These results support the idea that hydrophobic interactions between Hybrid/EGF-4 domain and peptide-anti tumor might contribute to stability of bended state and therefore inhibit integrin activation. Our finding can be applied to understand the mechanism of out-in pathway integrin signaling and development of integrin targeted drug.
Target Mutation of CD80 Protein to Enhance Its Binding to CD28 Receptor
Volume 11, Issue 1, Winter 2020, Pages 1-11
N. Pesaran Afsharian, Z. Hajihassan, N. Ansari-Pour
Abstract The CD80 protein, a member of the super-family of immunoglobulin, is a transmembrane protein expressed on the surface of the antigen-presenting cells (APC). This protein has two receptors on the surface of T cells (CTLA-4 and CD28), due to the binding of this protein to these receptors, the inhibitory and stimulatory pathway in the T cells begin, respectively. Naturally, CD80 proteins tend to have more binding affinity to CTLA-4 than CD28, and this is a factor in the extinction of T cells in the immune system in order to prevent autoimmunity. The aim of the present study is to create a variant of the CD80 protein that has an increased binding affinity to CD28 to bind to this receptor more strongly and induce more simulate pathways than the wild type of this protein (primary CD80 protein) in T cells. To identify this variant, first, the ancestral sequence was mutated by R software at positions 31 and 92 with amino acids that play an important role in the formation of hydrogen bonds. The R software output sequences were modeled with the SWISS-MODEL server. Then, each output model was docked with the HADDOCK server, and finally, the electrostatic and van der Waals energies between the receptors and the ligands were calculated. Among all the built-in models, the mutated K31Y, R92F has the best electrostatic and van der Waals energies and has the ability to have a much better connection to its CD28 receptor compared to the ancestral type of CD80.
A study on cytotoxicity, hemocompatibility, and antibacterial properties of tetracycline hydrochloride-loaded PCL-based composite scaffolds for bone tissue engineering
Volume 11, Issue 1, Winter 2020, Pages 61-69
Mahsa Bohlouli, Elnaz Tamjid, Soheila Mohammadi, Maryam Nikkhah
Abstract Since one of the main problems in bone tissue repair is the bacterial infections, recently the development of drug-eluting nanocomposite scaffolds for bone regenerative medicine applications has attracted significant attention. In this study Polycaprolactone (PCL)-based composite scaffolds containing 10vol% of titanium dioxide nanoparticles (~21nm), and bioactive glass particles (~6µm), were prepared without drug and also loaded by Tetracycline hydrochloride (TCH) antibiotic (0.57, 1.15 mg/mL) through solvent casting method for bone tissue engineering applications. Structural characterizations based on Scanning Electron Microscopy (SEM), and FTIR analysis were utilized to study the chemical bonds of glass/ceramic particles, and antibiotic crystals on the surface. In addition, in vitro cytotoxicity, and antibacterial analysis were performed by MTT, and Agar well-diffusion assays, respectively. In this study polymeric and composite scaffolds were fabricated with TCH clusters decorated on the surface. It was shown that the bioactive glass/PCL scaffolds loaded by 0.57 mg/mL of TCH revealed significant antibacterial effect, despite the acceptable cell viability. These scaffolds seem to be of interest as a potential candidate in drug-eluting scaffolds for bone tissue engineering applications.
Role of Probiotics in the Prevention and Control of Multiple Sclerosis
Volume 10, Issue 4, Autumn 2019, Pages 589-592
H. Pourkalhor, D. Farhud
Abstract Introduction: Since the gastrointestinal system plays an important role in the function of the immune system, its role in the control or treatment of autoimmune diseases cannot be ignored. Therefore, the intestinal strengthening, which much of gastrointestinal function depends on it, can be effective in this direction. Also, because the intestine plays an important role in the immune system in addition to digestion, it can help maintain the immune system's function by keeping its bacteria balanced. In this regard, probiotics and prebiotics can be useful, which this issue was investigated in the present study.
Conclusion: Probiotics have an important role in the prevention and control of multiple sclerosis.
The effects of Nanocurcumin on Expression Induction of Transcription Factors Involved in Hematopoietic Stem Cell Differentiation to Precursor Myeloid Cells
Volume 10, Issue 4, Autumn 2019, Pages 601-608
S.S. Mortazavi Farsani, M. Sadeghizadeh, H. Shirzad, F. Najafi
Abstract Aims: Hematopoietic stem cells are responsible for the production of blood cells in the bone marrow. During the process of differentiation, these cells commitment to two precursor cell lines include myeloid and lymphoid cells. Various blood cells, excluded lymphocytes, generates from myeloid cells. Some patients with severe anemia or thrombocytopenia receive hematopoietic stem cell through transplantation. Finding a potential component for inducing differentiation of hematopoietic stem cells before transplantation, could be an appropriate strategy for the acceleration of blood cells production in recipient persons. Various studies indicate the ability of Curcumin for inducing of cell differentiation. This component can alter many of cellular mechanisms.
Material and methods: The aim of this project was to evaluate the effects of Nanocurcumin on mRNA expression levels of GATA1, GATA2, c-Myb and Hhex genes and alteration of cellular ROS in umbilical cord blood-derived hematopoietic stem cells. Nanocurcumin was synthesized from Curcumin, Oleic acid, and PEG400. The rate of Nanocurcumin delivery into the cells was also evaluated.
Findings: Our results show that intracellular ROS and expression levels of GATA1, c-Myb, and Hhex transcription factors were significantly increased after treatment with Nanocurcumin (p<0.05). These transcription factors involve in myeloid differentiation.
Conclusion: Enhancement of these transcription factors expression making Nanocurcumin a potential candidate for applying in myeloid differentiation media and basic and clinical studies.
