Iranian Biomedical Journal
Volume:27 Issue: 2, May 2023

With the aim of providing community health, the Pasteur Institute of Iran was established in 1920 as the oldest medical and health research institution in Iran. In addition to conducting research relevant to infectious diseases and manufacturing biological products, this institute has significantly contributed to the prevention and control of communicable diseases for more than a century. As an elder in the institute, Dr. Mahdokht Pourmansour, a physician and specialist in microbiology and laboratory science, was a prominent researcher at the Pasteur Institute of Iran. During four decades of her service to the institute, she has performed remarkable activities, particularly in the development of the Bacille Calmette-Guérin vaccine to prevent tuberculosis. In this biography paper, her scientific life and services are reviewed.

Early life:

Mahdokht Pourmansour was born on January 7th, 1935 in Tehran, the capital city of Iran. She attended Mehregan and Asadi elementary schools in Tehran from 1940 to 1946. During the time periods 1946-1952, she continued her high school education at Nizam Vafa in Ahvaz and obtained her high school diploma at Azarm high school in Tehran. From 1952 to 1958, she received her doctorate in medicine from the University of Tehran. During the years 1967-1968, she attended the Pasteur Institute of Paris on a scholarship from the Pasteur Institute of Iran. After returning to the country in 1974, she presented the courses she took in France and obtained Ph.D. degree in clinical laboratory science at the University of Tehran. Her Ph.D. dissertation was written on the development of a cholera vaccine in laboratory animals.

The venom glands are a rich source of biologically important peptides with pharmaceutical properties. Scorpion venoms have been identified as a reservoir for the components which might be considered as great candidates for drug development. Pharmacological properties of the venom compounds have been confirmed in the treatment of different disorders. Ion channel blockers and AMPs are the main groups of scorpion venom components. Despite existence of several studies about scorpion peptides, there are still valuable components to be discovered. Additionally, owing to the improvement of proteomics and transcriptomics, the number of peptide drugs is steadily increasing, which reflects the importance of them. This review evaluates the available literatures about some important scorpion venom peptides with pharmaceutical activities. Given that the last three years have been dominated by the COVID-19 from the medical/pharmaceutical perspective, scorpion compounds with potential against the coronavirus 2 (SARS-CoV-2) are also discussed in this review.

MicroRNAs (miRNAs) are significant regulatory factors in stem cell proliferation, and change in miRNA expression influences the cancer stem cell viability and gene expression. Herein, we evaluated the effect of the hsa-miR-4270 inhibitor and its mimic on the expression of stem cell markers in gasteric cancer (GC) stem-like cells.

GC stem-like cells were isolated from the MKN-45 cell line by a non-adherent surface system. The cells were confirmed by differentiation assays using dexamethasone and insulin as adipogenesis-inducing agents and also Staurosporine as a neural-inducing agent. Isolated GC stem-like cells were treated with different concentrations (0, 15, 20, 25, 30, 40, 50, and 60 nM) of hsa-miR-4270 inhibitor and its mimic. The quantity of cell viability was determined by trypan blue method. Transcription of the stem cell marker genes, including CD44, OCT3/4, SOX2, Nanong, and KLF4 was evaluated by real-time RT-PCR.

The results showed that GC stem-like cells were differentiated into both adipose cells using dexamethasone and insulin and neural cells by Staurosporine. Treatment of GC stem-like cells with hsa-miR-4270 inhibitor decreased cell viability and downregulated OCT3/4, CD44, and Nanog to 86%, 79%, and 91% respectively. Also, SOX2 and KLF4 were overexpressed to 8.1- and 1.94-folds, respectively. However, hsa-miR-4270 mimic had opposite effects on the cell viability and gene expression of the stem cell markers.

The effect of hsa-miR-4270 inhibitor and its mimic on the expression of the stem cell markers in GCSCs indicated that hsa-miR-4270 stimulates the stemness property of GCSCs, likely through stimulating the development of gastric stem cells.

Post-translational modifications in bioprocessing and storage of recombinant mAbs are the main sources of charge variants. While the profile of these kinds of variants is considered an important attribute for the therapeutic mAbs, there is controversy about their direct role in safety and efficacy. In this study, the physicochemical and pharmacokinetic (PK) properties of the separated charge variants belonging to a trastuzumab potential biosimilar, were examined.

The acidic peaks, basic peaks, and main variants of trastuzumab were separated and enriched by semi-preparative weak cation exchange. A panel of analytical techniques was utilized to characterize the physicochemical properties of these variants. The binding affinity to HER2 and FcγRs and the PK parameters were evaluated for each variant.

Based on the results, the charge variants of the proposed biosimilar had no significant influence on the examined efficacy and PK parameters.

During the development and production of biosimilar monoclonal antibodies, evaluating the effect of their charge variants on efficacy and PK parameters is needed.

Infection is one of the significant challenges in medical implant-related surgeries. Despite systemic antibiotic therapies, bacterial growth after implantation may cause implant failure. Nowadays, unlike the systemic therapy, local controlled release of antibiotic agents is considered an effective approach for the prevention of implant-related infections. The present study aimed to develop a niosomal nanocarrier incorporated into fibroin films for local and continuous delivery of thymol, a natural plant-derived antimicrobial agent for preventing infections caused by implant-related.

Niosomes containing thymol were prepared by thin-film hydration technique. Thymol sustained release from the prepared films was assessed for 14 days. Antibacterial activities of the synthesized films were also evaluated by the agar diffusion technique against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus.

The release behavior from the niosomal thymol films showed a sustained manner, in which the amount of the released thymol reached 40% after 14 days. The films containing thymol with and without niosome showed a significant viability against L929 fibroblast cells compared to other groups after 24 and 48 h, using MTT assay. Also, samples exhibited potent antibacterial activity against Gram-negative and Gram-positive bacteria.

The results of this study demonstrate that the niosomal thymol-loaded fibroin film is a promising candidate for the controlled release of thymol and prevention of implant-related infection.

K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants, K-Ras4A and K-Ras4B, arise originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.

Total RNA was extracted from breast tumors, and the NATs were obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.

A statistically significant increase was found in K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).

Our findings reveal that the expression levels of K-Ras4A and
K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.

Different genotypes of Echinococcus granulosus sensu lato can infect humans and animals. The simultaneous occurrence of the isoenzymes and molecular characterization of this important zoonotic parasite have not been yet investigated in Iran. This study aims to evaluate the isoenzyme pattern of the larval stage of Echinococcus spp. genotypes according to their host types in the country.

Thirty-two (8 humans and 24 animals) hydatid cyst isolates were collected from May 2018 to December 2020. DNAs were extracted using a DNA extraction kit, and their genotypes were determined by molecular methods to identify the presence of different species/genotypes of E. granulosus sensu lato. Enzymes were extracted from the cyst and subjected to polyacrylamide gel electrophoresis. The activities of glucose 6-phosphate dehydrogenase (G6PD), malate dehydrogenase (MDH), malic enzyme (ME), nucleoside hydrolyse 1 (NH1), and isocitrate dehydrogenase (ICD) were assessed in the cyst samples. The results were compared with the genotyping findings.

DNA sequence analysis of the samples showed that the specimens contained 75% E. granulosus sensu stricto (G1) and 25% E. canadensis (G6) genotypes. The isoenzyme pattern of ICD for both genotypes produced a six-band pattern with different relative factors.  Moreover, the G6PD produced two bands with different relative migration in both genotypes. The MDH and NH1 systems exhibited a two-band pattern, while only one band was observed in the ME enzyme of the E. granulosus sensu stricto genotype. Furthermore, in E. canadensis, the MDH and NH1 enzymes showed one band, and the ME enzyme represented a two-band pattern.

Our findings reveal that E. granulosus sensu stricto and E. canadensis genotypes have entirely different isoenzyme patterns for NH1, G6PD, MDH, and ME. Therefore, these enzyme systems may be used for the differentiation of these two genotypes of Echinococcus granulosus.

Dyskeratosis congenita (DC), an inherited and rare disease prevalent in males, is clinically manifested by reticulate hyperpigmentation, nail dystrophy, and leukoplakia. DC is associated with the increased risk of malignancy and other potentially lethal complications such as bone marrow failure, as well as lung and liver diseases. Mutations in 19 genes were found to be correlated with DC. Herein, we report a 12-year-old boy harboring the NM_ 001099274.3(TINF2): c.844C>T (p.Arg282Cys) mutation found by whole exome sequencing. There was no history of the disease in the family and the variant was classified as a de novo mutation.

Considering the high prevalence and clinical importance of herpes simplex virus (HSV) infection worldwide, we aimed to evaluate the seroprevalence of HSV-1 and HSV-2 in a population aged between 15 and 35 years in Mashhad, Iran.

This cross-sectional study was conducted on 916 cases composed of 288 (31.4%) men and 628 (68.6%) women. Using ELISA method, the presence of IgM and IgG antibodies against HSV-1 and HSV-2 was assessed.

Among the population studied, 681 (74.3%) cases were positive for anti-HSV antibodies, while 235 (25.7%) cases were negative. Moreover, no IgMs were found and all positive subjects had IgG antibodies. Age (p < 0.001), occupation (p < 0.001), education (p = 0.006), smoking (p = 0.029), and BMI (p = 0.004) demonstrated a significant association with HSV-1 and HSV-2 infection.

Our study indicates a high seroprevalence of HSV infection; however, there was no cases positive for IgM antibodies, suggesting the high prevalence of latent infection.