Iranian Biomedical Journal
Volume:26 Issue: 2, Mar 2022

Dr. Abolghasem Bahrami was among the generation of Iranian scientists in the early twentieth century who gained most of their knowledge through resources available inside the country. Educated at Dar-ul-Funun Medical School, he was a physician with a great talent in learning, especially self-teaching natural sciences and European languages. He joined the Pasteur Institute of Iran (IPI) at the early days of its foundation and became an integral contributor to this institution during the first twenty-five years of its mission. One of his first assignments at IPI was to help initiating an anti-rabies department by bringing back the rabies vaccine and its manufacturing equipment from Institut Pasteur of Paris. During his IPI years, aside from managerial tasks, he actively participated in upgrading the medical treatments and protocols used for controlling many infectious diseases. He functioned twice as the provisional director of IPI (1925-1926 and 1937-1946) and is considered as the first Iranian director of the Institute. Meanwhile, Dr. Bahrami was a significant contributor to the public health system and assumed several responsibilities such as Chief Quarantine Medical Officer, Chief of Public Health, and the Head of Public Health Administration, in order to improve public health planning throughout the country.

The heterogeneity of CD4+ T cells has been investigated since the late 1970s, when their Th1 and Th2 subsets were coined. Later studies on the cutaneous form of the Leishmaniasis were focused on the experimental models of Leishmania major infection using the susceptible BALB/c and the resistant C57BL/6 mice. At the early 21st century, the regulatory T-cells subpopulation was introduced and its role in concomitant immunity, responsible for lifelong resistance of the host to the reinfection was proposed. Subsequent studies, mainly focused on the visceral form of the infection pointed to the role of IL-17, produced by Th17 subset of CD4+ T cells that along the neutrophils were shown to have important yet equivocal functions in protection against or exacerbation of the infection. Altogether, the current knowledge indicates that the above four subsets could orchestrate the immune, the regulatory and the inflammatory responses of the host against different forms of leishmaniases.

Lithium is a therapeutic option for the treatment of the acute phase of the bipolar disorder and long-term management of this disorder. However,  it  is  estimated  that  10  to  60%  of  patients  do  not  properly response to this medication.

To investigate the role of MARK2 gene in response to lithium, we genotyped the MARK2 rs10792421 polymorphism in Iranian bipolar patients using amplification Refractory Mutation System-PCR.

Results of this study showed a significant association of this polymorphism with response to lithium. The A allele was more frequent in the  responder  than  the  non-responder  group  and  also  in  the  semi- responder group compared to the non-responder group in the codominant model of analysis. AA and AG genotypes were more frequent in both the responder and semi-responder groups compared to the non-responder group in dominant model of analysis.

Based on the findings of the current study, the rs10792421 variant of MARK2 gene could be considered as a potential biomarker for predicting the treatment outcome of bipolar disorder type 1 in Iranian population.

In the present study, a tissue engineered silk fibroin (SF) scaffold containing simvastatin-loaded silk fibroin nanoparticles (SFNPs) were used to stimulate the regeneration of the defected bone.

At first, the porous SF scaffold was prepared using freeze-drying. Then simvastatin-loaded SFNPs were made by dissolvation method and embedded in the SF scaffold. Afterwards, the scaffold and the NPs were characterized in terms of physicochemical properties and the ability to release the simvastatin small molecule.

The results exhibited that the SF scaffold had a porous structure suitable for releasing the small molecule and inducing the proliferation and attachment of osteoblast cells. SFNPs containing simvastatin had spherical morphology and were 174 ± 4 nm in size with -24.5 zeta potential. Simvastatin was also successfully encapsulated within the SFNPs with 68% encapsulation efficiency. Moreover, the small molecule revealed a sustained release profile from the NPs during 35 days. The results obtained from the in vitro cell-based studies indicated that simvastatin-loaded SFNPs embedded in the scaffold had acceptable capacity to promote the proliferation and alkaline phosphatase production of osteoblast cells while inducing osteogenic matrix precipitation.

The SF scaffold containing simvastatin-loaded SFNPs could have a good potential to be used as a bone tissue-engineered construct.

Inflammatory bone resorption in periodontitis can lead to tooth loss. Systemic administration of bisphosphonates such as risedronate for preventing bone resorption can cause adverse effects. Alginate hydrogel (ALG) and poly (lactic acid-co-glycolic acid) (PLGA) microparticles have been studied as drug delivery systems for sustained release of drugs. Therefore, the release pattern of risedronate from PLGA microparticles embedded with ALG was studied as a drug delivery system for sustained release of the drug, which can be used in local administrations.

Risedronate-containing PLGA microparticles were fabricated using double emulsion solvent evaporation technique. Ionic cross-linking method was used to fabricate risedronate-loaded ALG. Risedronate-containing PLGA microparticles were then coated with ALG. The calibration curve of risedronate was traced to measure encapsulation efficiency (EE) and study the release pattern. Scanning electron microscope (SEM) imaging was carried out, and cell toxicity was examined using MTT assay. Statistical analysis of data was carried out using SPSS ver. 20 software, via one-way ANOVA and Tukey’s tests.  

SEM imaging showed open porosities on ALGs. The mean EE of PLGA microparticles for risedronate was 57.14 ± 3.70%. Risedronate released completely after 72 h from ALG, and the cumulative release was significantly higher (p = 0.000) compared to PLGA microspheres coated with ALG, which demonstrated sustained released of risedronate until day 28. Risedronate-loaded ALG showed a significant decrease in gingival fibroblasts cell viability (p < 0.05).

Alginate-coated PLGA microspheres could release risedronate in a sustained and controlled way and also did not show cell toxicity. Therefore, they seem to be an appropriate system for risedronate delivery in local applications

Immobilization is an approach in industry to improve stability and reusability of urease. The efficiency of this technique depends on the type of membrane and the method of stabilization.

The PEI-modified egg shell membrane was used to immobilize urease by absorption and glutaraldehyde cross-linking methods. The membranes were characterized by Fourier-transform infrared spectroscopy (FTIR) and AFM, and Nessler method was applied to measure the kinetic of the immobilized enzymes. Finally, the storage stability (6 °C for 21 days) and reusability (until enzyme activity reached to zero) of the immobilized enzymes were investigated.  

Based on FTIR, three new peaks were observed in both the absorption- (at 1389.7, 1230.8, and 1074.2 cm-1) and the cross-linking (at 1615-1690, 1392.7, 1450 cm-1) immobilized enzymes. The surface roughness of the native membrane was altered after PEI treatment and enzyme immobilization. The optimal pH of cross-linking immobilized enzymes was shifted to a more neutral pH, while it was alkaline in adsorption-immobilized and free enzymes. The reaction time decreased in all immobilized enzymes (100 min for free enzyme vs. 60 and 30 min after immobilizing by adsorption and cross-linking methods, respectively). The optimal temperature for all enzymes was 70 °C and they had a higher Km and a lower Vmax than free enzyme. The stability and reusability of urease were improved by both methods.

Our findings propose these approaches as promising ways to enhance the urease efficiency for its applications in industries and medicines.

Stenotrophomonas maltophilia is an opportunistic bacterium, contributing to different hospital-acquired infections and can be acquired from different hospital setting sources. Epidemiological study of S. maltophilia in the hospital also demonstrates the intrahospital distribution of certain strains of bacteria in healthcare facilities. The aim of the current study was to identify the molecular epidemiology of S. maltophilia isolates from clinical and environmental sources within a hospital.  

A total of 400 samples (clinical and environmental) were collected from the different settings of hospital. Following the standard biochemical testing and 23S rRNA genotyping, the molecular typing of S. maltophilia isolates was determined using the multilocus sequence typing (MLST) technique. Also, the frequencies of zot and entF virulence genes among S. maltophilia isolates were examined by PCR technique.  

Based on the biochemical testes and PCRs targeting 23S rRNA gene, 22 S. maltophilia isolates were identified. The MLST analysis demonstrated that these isolates were assigned to 14 ST, and 6 out of 14 STs were common among clinical and environmental samples. All 22 isolates were identified in the PubMLST database. The PCR screening demonstrated that none of 22 S. maltophilia isolates had zot virulence gene, while the entF gene with the 59% frequency was observed in 13 out of 22 isolates. Among these 13 isolates, 6 STs were common in clinical and environmental isolates.

Our study showed the clonal relatedness between clinical and environmental sources of the S. maltophilia isolates in a hospital. Further studies are required to understand the epidemic situation of this pathogen in the clinic and the environment.

Lipase enzymes are of great importance in various industries. Currently, extensive efforts have been focused on exploring new lipase producer microorganism as well as genetic and protein engineering of available lipases to improve their functional features.

For screening lipase-producing lactobacilli, isolated strains were inoculated onto tributyrin agar plates. Molecular identification of lipase-producing Lactobacilli was performed by sequencing the 16Sr DNA gene, and a phylogenetic tree was constructed. The LAF_RS05195 gene, encoding lipase protein in L. fermentum isolates, was identified using specific primers, amplified by PCR (918 bp) and cloned into the pET28a (+) vector. The recombinant proteins were expressed 2, 4, 6, and 12 hours after induction with IPTG and assessed using the SDS polyacrylamide gel electrophoresis (SDS-PAGE). Enzymatic activity of the purified recombinant protein was measured at 410 nm in the presence of ρ-NPA and ρ-NPP.  

Among five identified native lipase-producing isolates, one isolate showed 98% similarity with Enterococcus species. The other four isolates indicated 98% similarity to L. fermentum. After purification steps with Ni-NTA column, a single protein band of about 34 kDa was detected on SDS-PAGE gel. The enzymatic activity of purified recombinant protein alongside ρ-NPA and ρ-NPP was measured to be 0.6 U/ml and 0.2 U/ml, respectively.

In the present research, a novel lipase/esterase from L. fermentum was cloned and expressed. The novel lipase/esterase has the merit to be further studied due to its substrate specificity.

Triple-negative breast cancer (TNBC) is determined by the absence of ERBB2, estrogen and progesterone receptors’ expression. Cancer vaccines, as the novel immunotherapy strategies, have emerged as promising tools   for treating the advanced stage of TNBC. The aim of this study was to evaluate Carcinoembryonic antigen (CEA), Metadherin (MTDH), and Mucin 1 (MUC-1) proteins as vaccine candidates against TNBC.

In this research, a novel vaccine was designed against TNBC by using different immunoinformatics and bioinformatics approaches. Effective immunodominant epitopes were chosen from three antigenic proteins, namely CEA, MTDH, and MUC-1. Recombinant TLR4 agonists were utilized as an adjuvant to stimulate immune responses. Following the selection of antigens and adjuvants, appropriate linkers were chosen to generate the final recombinant protein. To achieve an excellent 3D model, the best predicted 3D model was required to be refined and validated. To demonstrate whether the vaccine/TLR4 complex is stable or not, we performed docking analysis and dynamic molecular simulation.

Immunoinformatics and bioinformatics evaluations of the designed construct demonstrated that this vaccine candidate could effectively be used as a therapeutic armament against TNBC.

Bioinformatics studies revealed that the designed vaccine has an acceptable quality. Investigating the effectiveness of this vaccine can be confirmed by supplementary in vitro and in vivo studies.