Biomacromolecular Journal
Volume:8 Issue: 1, Summer 2022

Furin is a serine protease that takes part in the processing and activation of the host cell pre-proteins. The enzyme also plays an important role in the activation of several viruses, such as the SARS-CoV-2 virus, the causative agent of COVID-19 disease which inflicted a high rate of mortality. Unlike other viral enzymes, furin has a constant sequence and active site characteristics and seems to be a better target for drug design for COVID-19 treatment. Considering furin active site as receptor and some approved drugs as ligands, we have carried out docking experiments in HEX software to pick up those which are capable of binding furin active site with high affinity. The tested drugs were chosen from different classes, including antivirals, antibiotics, and anti-protozoa/anti-parasites with suspected beneficial effects on COVID-19. Our docking experiments show that saquinavir, nelfinavir, and atazanavir with respective cumulative inhibitory effects of 2.52, 2.16, and 2.13, respectively are the best candidates for furin inhibition. Clarithromycin, niclosamide, and erythromycin show cumulative inhibitory indices of 1.97, 1.90, and 1.84, respectively. Considering the lower side effects of clarithromycin, niclosamide, and erythromycin in contrast to the antivirals such as saquinavir, nelfinavir, and atazanavir, we suggest the formers as prophylaxes and even at severe states of COVID-19 as adjuvant therapy.

One of the important issues for quality control of biological products is purity. In most cases, electrophoresis is used to determine the purity of the proteins and the quantity of related band is determined by densitometry and respective software. In order to check the purity of hyperimmune plasma and antivenom bulks, we have evaluated the albumin content of these products. Sixty samples were divided into two groups: the hyperimmune plasma group that containing thirty bulks of monovalent and polyvalent anti-snake, polyvalent anti-scorpion and anti-diphtheria toxin plasma, and plasma-derived antivenoms group, comprising thirty bulks sera obtained from the purification of relevant plasma bulks. The albumin purification from horse normal serum was performed through heat shock strategy and used as reference for the quantification of albumin content. After electrophoresis of samples, the gel images were analyzed using Image J software and the amount of protein in relevant band was determined by calculating the curve area and comparison with reference albumin. The results revealed significant changes on albumin level in hyperimmune plasma samples. Two out of 30 plasma samples had lower and sixteen samples had a higher albumin than normal levels. Using the Image J, we could not detect any residue of albumin in antivenom sera. The results demonstrated effectiveness of purification protocol for removal of albumin during antivenom production process. However, development of a quantitative evaluation method along with the semi-quantitative method used in this study can help the accuracy of these results.

Breast cancer is one of the most common cancers in women; whose mortality rate has remained high despite medical advances. The present study is aimed to evaluate the antitumor activity of caffeic acid (CA) and methylseleninic acid (MSA), separately and in combination, on the triple-negative human Caucasian breast adenocarcinoma cell line (MDA-MB -231). To evaluate the cytotoxicity of CA and MSA on the growth and proliferation of breast cancer cells, and the rate of cell survival, the MTT test was carried out. DAPI staining was used to determine the type of death induced in the MDA-MB-231 cells. The effect of caffeic acid and methyl seleninic acid on apoptosis was investigated in triple-negative Caucasian breast adenocarcinoma cell lines (MDA-MB- 231) by flow cytometry. Based on the results of the MTT assay, IC50 values of 40 and 30 µg/ml were calculated for both CA and MSA on MDA-MB -231 cell line after 24 and 48 h, respectively. Based on the results of this study, caffeic acid and methylseleninic acid inhibited MDA-MB-231cell proliferation and induced apoptosis in these cells in a dose-dependent manner by increased Bax/Bcl2 level. Morphological studies also showed apoptosis characteristic features in MDA-MB -231cell after treatment with CA and MSA. Our findings indicated that CA and MSA had significant anti-tumor activity separately and in lower dose in combination . CA is effective in treating breast cancer at lower concentrations if used in combination with MSA.

Nanotechnology has been researched over the past decades for green synthesis of iron oxide nanoparticles(IONPs); revealing the significance of plant extracts in reducing the iron precursor salt to nanoparticles and their applications in various domains. Zhumeria majdae(Mohre-khosh) is an aromatic herb, belonging to the family Lamiaceae that grows wild just in Hormozgan Province, southern Iran. It has reported that the leaves of Zhumeria majdae contain phytocompounds like flavonoids, diterpenoids and triterpenes. Herein, the leaves of Zhumeria majdae are used for the first time as a reducing agent. Present work emphasized on the synthesis of iron oxide nanoparticles using Zhumeria majdae leaves for targeted drug delivery for breast cancer. IONPs were characterized and their Cytotoxicity effects were srudied on the breast cancer cell line MCF-7 and Human embryonic kidney (Hek293). The use of the metabolic extract of Zhumeria majdae leaf indicated the involvement of phytocompounds in reducing the iron oxides and capping and stabilizing their nanoparticles. Finally, cytotoxicity assay revealed that the obtained IONPs have potential cytotoxicity against breast cancer cell line of MCF-7.

A plant of the Apocynaceae family, Gymnema sylvestre, is included and used as a traditional therapy for various purposes. It is being used as a dietary supplement because it has numerous therapeutic benefits. In this paper, reviews mainly focused on Gymnema sylvestre and its bioactive components effect on human cancer cell (in vitro) and oxidative stress. In order to write this review which provides a comprehensive review of Gymnema sylvestre showing promising anticancer and antioxidant activity relevant information was collected from scientific journals, and research papers. Due to the presence of bioactive compounds in Gymnema sylvestre such as flavonol glycoside, lupeol, sterols, triterpenoid saponins, dammarene saponins and triterpene saponins, it can act as a promising cytotoxic and anticancer agent against several human cancer cell lines. Therefore, G. sylvestre has been shown to be effective against cancer development and progression and oxidative stress, and should be considered safe and effective to use in cancer prevention and therapy and as an antioxidant.

One family of anti-apoptotic proteins named the inhibitor of apoptosis proteins (IAPs) prevents cell death by blocking the downstream region of the caspase activation pathways. Survivin is a small member of the family of proteins that suppress apoptosis. Survivin performs various tasks that help cancer cells survival, including cytoprotection, preventing cell death, and controlling the cell cycle, particularly during the mitotic process. Cancer cells may survive with the help of survivin, as it is consistently up-regulated in human tumors, connected to poor prognosis, resistance to chemotherapy or radiation therapy, and associated with these treatments. Survivin is often regulated at two levels: the transcriptional level and the post-translational levels. In this review, the different proteins influence the progression of survivin degradation in post-translation adjustment were discussed such as FAT10, Usp22, Csn5; and LNC473. Finding and developing a therapy strategy that can adequately address the range of the aforementioned issues might be aided by understanding regulators and their mechanisms of action.

Multiple sclerosis (MS) is a chronic disease of the central nervous system that leads to the disability of the affected people. The etiology of the disease is not clear, but it is believed that it has an autoimmune nature. Several studies suggested that the major histocompatibility complex (MHC) class II loci are the most prominent genetic risk factor for MS susceptibility. The Human leukocyte antigen (HLA) DQB1*06 allele was introduced in numerous studies as the MS genetic predisposition factor, but there is a debate about it in different regions. This study aims to analyze the association of the HLA-DQB1*06 allele in Tehran. Blood samples were collected from 117 MS and 114 healthy people. DNA was extracted, and genotyping was performed using allele-specific primers. Our results showed that the HLA-DQB1*06 allele is significantly associated with MS (p-value < 0.000, odds ratio = 0.059, 95% CI = 0.02 to 0.14). The homozygous genotype was also more prevalent in the MS group compared with the control (p-value < 0.000, odds ratio = 0.2, 95% CI = 0.1- 0.39). Our results show no difference in allelic distribution of this gene between men and women. Our data suggest that the HLA-DQB1*06 could be considered as an important genetic risk factor for MS in Tehran.

The most important issue in diagnosing human breast cancer is the ability to detect the early stages of cancer, which can help the healing process. Therefore, new diagnostic methods for breast cancer focus on molecular approaches. The aim of this work is to develop the NABA-ELISA method for the diagnosis of breast cancer in clinical samples, which is used for the first time to evaluate HER2, ER and SPATA19 biomarkers simultaneously. The possibility of expressing the SPATA19 gene, a specific biomarker for testis cancer, was also investigated in breast cancer. Specific primers and biotinylated probes were designed separately for each of the target genes. RT-PCR and NASBA reactions were done on total RNA extracted from the clinical tumor tissues. The DIG-labeled NASBA product was detected by the ELISA method using the biotinylated probe and anti-DIG antibody-enzyme conjugate. The ELISA reaction showed obvious color change and significant absorption in the positive samples. Of 15 samples tested; 11, 4 and 3 samples were positive for ER, HER2 and SPATA19 genes, respectively. Comparison of real-time RT-PCR with NASBA-ELISA showed the same results for both ER and HER2 genes. There was no significant relationship in the expression of the SPATA19 gene with ER and HER2 genes in these specimens. Also, no significant relationship was observed between SPATA19 gene expression and breast cancer in these samples. In this study, we developed a simple, fast, and reliable NASBA-ELISA method that can detect cases of breast cancer.

Problems with coagulation factor X (FX) inherited in families. Consanguineous marriage is common in Iran, therefore one may predict a greater prevalence rate there than in the Western populations. FX represent a category of very uncommon bleeding diseases caused by defects in the factor X (F 10) gene. Blood clots can't form without factor X, an essential protein in the coagulation cascade. Factor X deficiencies or abnormalities may cause aberrant bleeding behaviors and provide substantial clinical management problems. Autosomal recessive inheritance pattern characterizes the F10 gene. To examine potential deleterious effects on encoded proteins, in silico approaches were applied. All exons and their boundaries of patients sample were sequenced using Sanger sequencing. Members of the family were also tested. F10 gene sequencing revealed several novel mutations. In addition, the disease-causing properties of the identified mutations were validated via segregation analysis and in-silico evaluations. Inherited coagulation factor X disorder is a rare bleeding disorder caused by FX protein deficiency or absence. These results would help affected families and those who are carriers for similar mutations. Prevention of morbidity and improvement of affected people' quality of life depends on prompt diagnosis and effective care.