نشریه زیست فناوری دانشگاه تربیت مدرس
سال دوازدهم شماره 4 (پیاپی 31، پاییز 1400)

Breast cancer is the leading cause of cancer-related mortality among women worldwide. In Iran, breast cancer ranks first among cancers diagnosed in women comprising 24.4% of all malignancies. Currently, the large number of etiological factors and the complexity of breast cancer present challenge for prevention and treatment. Breast cancer tumorigenesis can be described as a multi-step process in which a normal cell undergoes malignant transformation to a fully developed tumor through accumulations of genetic and epigenetic changes. On the other hand, several studies indicated the signaling pathways role in Breast cancer. EGFR gene has been shown to be overexpressed in breast cancer. Dimerization of EGFR/HER2 induces breast cancer progression via activation of PI3K/AKT signaling cascade. MicroRNAs are endogenous, small non-coding RNAs that regulate gene expression at the transcriptional and posttranscriptional level. MicroRNAs pair with partially complementary sites in the 3′untranslated regions (UTRs) of target mRNAs, leading to translational repression and/or mRNA degradation. In present study we applied bioinformatics data to predict miR-1226-3p as the regulator of PI3K/AKT pathway. Then significant down regulation of three target genes EGFR, PIK3R5 and AKT2 was observed post transfection of miR-1226-3p. To validate the effect of this down regulation on cells, expression of downstream genes PCNA, C-MYC and CCND1 was evaluated. Down regulation of these genes demonstrated that cell proliferation in this breast cancer cell line was inhibited and this miRNA could be considered as a tumor suppressor.

Premature ovarian failure (POF) is one of the most important reproductive diseases in women under 40 years of age, which affects the quality of life and longevity of these people by causing short-term and long-term complications.
The incidence of POF is a chronic process that takes several years to develop. The patient went through stages such as premature ovarian insufficiency (POI) and decreased ovarian reserve (DOR), in the early stages of the disease decreased ovarian function efficiency (POI) and then with further progression of the disease, the patient decreased ovarian reserve and further reduce their performance. As the disease progresses, the person eventually develops premature and complete ovarian failure, or POF studies have shown that many factors, including surgical trauma, autoimmune diseases, certain drugs, vaccines, and genetic factors, play a role. Genetic studies have shown that several genes are involved in the development of this disease. Part of the regulation of the expression of these genes is the responsibility of small genetic factors called miRNAs.

In the present study, bioinformatics information of miRNAs involved in this disease was investigated. For this purpose, genetic databases such as UCSC, NCBI, KEGG, MIRBASE, TARGET SCAN, STRING, etc. were used to access the genes involved in this disease, structural and functional communication, messaging pathways and regulatory miRNA.
Results and

The results of this study indicate that three factors, miRNA-187, miRNA-33b and miRNA-33a, are very effective in the development and progression of this disease.

Spectral properties and thermal stability of AS1411 G-quadruplex AS1411 is an anticancer four-stranded deoxyoligonucleotide with high affinity and specificity to a putative surface biomarker, nucleolin, which is an overexpressed protein on numerous cancer cells. AS1411 has valuable functional potential for the targeted delivery of nanoparticles, oligonucleotides, peptides and small drug molecules to cancer cells. Considering that understanding interaction of drug with target molecule is important and necessary for pharmaceutical studies, in the present study, the interaction of a porphyrin photosensitizer called TMPYP4 was evaluated with aptamer AS1411. Absorption and fluorescence spectroscopy and circular dichroism technique were used to identify how and where TMPYP4 binds to AS1411 and the resulting structural changes. The results showed that binding of the porphyrin to AS1411 caused 13 nm red shift and 56% hypochromicity in the absorption spectrum; in addition, due to this binding, the emission spectrum of porphyrin is changed and its emission intensity is reduced. The results of structural studies showed that the binding of TMPYP4 does not significantly change the shape of the AS1411 circular dichroism spectrum, but at high concentrations leads to an intense decrease in the intensity of the spectrum. These changes in the spectra indicate that TMPYP4 binds to the aptamer through intercalation between tetrad planes and end-staking and causes to opening of the aptamer structure. As a conclusion, it can be proposed that AS1411 aptamer has appropriate potential for delivery of porphyrin compounds and their photosensitizer types and can be used in photodynamic therapy of cancer cells.

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.

The aim of this study was to isolate and identify a-amylase-producing bacteria present in mangrove ecosystems on Qeshm Island, Hormozgan, Iran. Samples of mangrove leaves and roots were screened for a-amylase activity using Lugol’s solution. Crude extracts were prepared of positive samples, and their a-amylase activity was determined by the Bernfeld method. The two strains with the highest activity were identified by molecular analysis of their 16S rRNA genes. a-Amylase production and activity were optimized by varying temperature and pH. 46 bacterial strains were isolated from mangrove tree leaf and root samples. Of these, 28 strains were capable of producing a-amylase. 16S rRNA gene sequence analysis of two strains with the highest enzyme production identified them as Bacillus sp. strain HR10 and Bacillus sp. strain HR11. The optimum temperature for enzyme production was 35 and 30 °C for strains HR10 and HR11, respectively, and the optimum pH was pH 8 for both strains. The highest enzyme activity was observed at 70 °C and 60 °C for the HR10 and HR11 strains, respectively, and the optimum pH was pH 8 for both strains. In conclusion, we have shown that bacteria isolated from mangrove leaf and root samples are potential source of a-amylases, tolerating a wide range of temperature and pH. Such a-amylases may be of interest for use in environmentally friendly industries.

Today, using fungi as source of bioactive compounds such as proteins for biosynthesis of different types of nanoparticles is being developed. In this study the characteristics of the biosynthesized zirconia nanoparticles (ZrO2 NPs) using Saccharomyces cerevisiae and Colletotrichum gloeosporioides were compared. Extracellular biosynthesis of ZrO2 NPs was carried out by adding 1 mM of K2ZrF6 to S. cerevisiae and C. gloeosporioides culture medium separately. Nanoparticle biosynthesis was confirmed by visual observation of color and transparency changes in the culture medium, UV-Vis spectrophotometry and XRD. FTIR results demonstrated the effects of some possible secretory compounds of the fungi such as protein, phenol and alcohol in the biosynthesis and stability process of the biosynthesized ZrO2 NPs. The results of elemental analysis (EDAX) confirmed the biosynthesis of zirconia nanoparticles as well as the presence of some elements in organic compounds participating in the biosynthetic process. The effect of time on the biosynthesis of the nanoparticles was also investigated. The color and transparency changes of the culture media, peak formation at less than 300 nm in spectrophotometry confirmed the extracellular biosynthesis of ZrO2 NPs and also XRD results confirmed the crystalline nature of the biosynthesized ZrO2 NPs based on their crystallite size. The FESEM results showed that the most of the nanoparticles were amorphous and some were monoclinic in shape with sizes (19.49 and 35.60 nm) for C. gloeosporioides and (45.81 and 74.07 nm) for S. cerevisiae. The monoclinic structure of the biosynthesized nanoparticles was confirmed by UV, FTIR and XRD results.

Summery
       Lentinula edodes(Shitake) is one of the most popular species of edible/medicinal fungus due to its high content of protein, polysaccharide and unique aroma, which is ranked second in the world in terms of cultivation and consumption. Today, its effective compounds are used as adjunctive therapy along with chemical treatments. In this study, the culture medium, acidity and optimum growth temperature of Lentinula edodes (TMU340) mycelium were determined. Mycelium, fruiting body and whole fungi were lyophilized and the wet to dry weight ratio was obtained; Lentinan was extracted using hot water at 60°C, degassing by Sevage method and precipitation with pure ethanol at 4°C and purified by Ion exchange chromatography. Lentinan concentration was obtained by phenol-sulfuric acid test. Results, Optimum conditions including PDA and PDB media, 25°C and pH, 5.5 were determined. The wet to dry weight ratio was 10 to 1 in all samples. Lentinan concentrations after extraction and purification were 0.243, 0.103 and 0.148 mg/ml, respectively. As a result, this fungus can be useful in the production of a variety of metabolites and natural compounds without side effects such as Lentinan polysaccharide as a factor in boosting the immune system.

MicroRNAs are a group of small non-coding RNAs that regulate gene expression in eukaryotes at the post-transcriptional level. MicroRNAs, through regulating the expression of large numbers of mRNAs, act as major regulators of various biological processes such as embryonic development, cell proliferation, differentiation, and apoptosis. Therefore, the identification of microRNAs and their target genes is very effective in finding the mechanisms of embryonic development, growth, and also the processes underlying the induction and progression of various diseases. Because of the high costs of molecular experiments, the identification of effective microRNAs through bioinformatics tools and computational biology is faster and cheaper than the experimental methods. Several online bioinformatics tools and databases have been developed and are freely available for predicting microRNAs target genes. The available online tools use a broad range of information, including sequencing data, gene expression data, and computational algorithms for predicting microRNAs target genes. Some of the most important of these online tolls are miRWalk, TargetScan, RNAhybrid, Diana-microT, miRanda, and MirTarget. The four main features of the interaction between a microRNA and an mRNA, including seed pairing, sequence conservation, free energy, and access to the binding site in a target are used in the algorithm of all of these prediction tools. This stud aimed to review the latest findings on the characteristics and capabilities of microRNA target prediction tools, comparing the performance of these tools, and finally introducing the most efficient tool in the field of target gene prediction for bioinformatics, biomedicine, and molecular medicine studies.

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.