Research in Molecular Medicine
Volume:9 Issue: 4, Nov 2021

ChAdOx1 nCov-19 vaccine is a viral vector-based vaccine with desirable protection (about 70.4% two weeks after the second dose). There were few reports on thrombocytopenia associated with thrombotic events shortly after ChAdOx1 nCov-19 vaccination. However, the exact pathophysiologic mechanism of this vaccine-induced thrombotic complication has not been yet elucidated. Vaccine induced thrombotic thrombocytopenia syndrome (VITTS), is associated with the detection of anti-PF4 antibodies, and is not still linked to the previous exposure to heparin.

In the current review, based on relevantly reported cases, possible mechanisms are suggested which provide a relationship between the results of anti-platelet factor 4 (anti-PF4) antibody assays, previous exposure to heparin, and the involved mechanisms of post-vaccination thrombocytopenia and thrombotic events, which might help the experts for selection of the appropriate therapeutic measures.

Possibly involved mechanisms in VITTS after ChAdOx1 nCoV-19 vaccination include binding of anti-PF4 antibodies to heparin/PF4 complex or to receptor binding domain (RBD) protein/PF4 complex. Additionally, binding of anti-RBD antibodies to RBD protein/PF4 complex could be considered as another mechanism. Finally, anti-RBD or anti-PF4 antibodies may bind to heparin/RBD protein/PF4 complex. Binding of either of the mentioned antibodies to these complexes via the Fc/ Angiotensin-converting enzyme 2 (ACE2) receptors can cause activation/removal of platelets leading to thrombocytopenia and thrombosis.

The suggested mechanisms in this article provide a relationship between the results of anti-PF4 antibody assays, previous exposure to heparin, and the involved mechanisms of post-vaccination thrombocytopenia and thrombotic events, which might help the experts for selection of the therapeutic measures.

Due to high genetic variation in human leukocyte antigen )HLA( alleles, epitope-based vaccines don’t show equal efficacy in different human populations. therefore, we proposed a multi-epitope vaccine against SARS-CoV-2 for Iranian populations.

For this purpose, the proteins without allergenicity and high antigenicity as well as conservancy level from SARS-CoV-2 were subjected to in silico B- and T-cell epitope mapping. T-cell epitope mapping process was performed based on the most frequent human leukocyte antigen (HLA) alleles in Iran. The B- and T-cell epitopes were screened based on their allergenicity, antigenicity and hemolytic potential and the epitopes with appropriate properties were subjected for final vaccine construct. The screened B- and T-cell epitopes were organized in the final vaccine construct. The secondary and tertiary structures of the proposed vaccine were predicted and its affinity to HLA-I, HLA-II, toll like receptor (TLR-3) and TLR-4 by molecular docking method. Additionally, probable immune responses against the vaccine were predicted trough immune simulation.

The final vaccine construct was includes six, eight and six linear B-cell epitopes, HLA-I restricted epitopes and HLA-II restricted epitopes respectively. The results of evaluations confirmed that the proposed vaccine is a 60.3 kDa stable, water soluble and high antigenic protein with high affinity to the selected target molecules and could elicits both humoral and cellular responses.

Altogether, the study suggests that the proposed vaccine can be considered as an effective anti-COVID-19 vaccine candidate for Iranian population.

A most common opportunistic pathogen, Pseudomonas aeruginosa is present in both humans and animals and responsible for various nosocomial infections and healthcare settings related infections. Different virulence genes like; oprL (membrane lipoprotein L) and toxA (exotoxin A i.e. ETA) in P. aeruginosa, assist in its pathogenicity, toxicity and contribute to high antibiotic resistance. So considering the risk of zoonotic transmission of P. aeruginosa through animal-related foods, this study aimed to monitor the prevalence of oprL and toxA virulence genes and antimicrobial resistance in P. aeruginosa isolates, obtained from animal (Cow’s milk) and human clinical samples.

Of the total 120 collected samples for this study, every 60 samples were collected from animals and humans from respective laboratories. Total 76 isolates of P. aeruginosa were isolated and identified by morphological and biochemical tests. The presence of virulence factors like oprL and toxA were evaluated by PCR analysis and antimicrobial resistance was assessed by antibiotic susceptibility test (Kirby-Bauer method).  

From the total 76, P. aeruginosa isolates obtained from both animal and human isolates, alone presence and coexistence of both toxA and oprL genes in P. aeruginosa isolates; were detected in PCR analysis. PCR analysis results showed in P. aeruginosa isolates, alone distribution of toxA and oprL genes is, 75% and 54.16% in animals, and 84.61% and 80.76% in humans, respectively. The coexistence of both genes was 37.50% and 40.32% in animals and human isolates, along with high antibiotic resistance in most P. aeruginosa isolates.  

Therefore, this study suggested PCR analysis can be used for fast and specific detection of oprL and toxA genes in P. aeruginosa. Monitoring of these genes can help to prevent the risk of transmission of multi-drug resistant P. aeruginosa, from animals to humans.

Despite its effectiveness, there are still many concerns and questions about the principles and therapeutic methods of traditional medicine (TM). In other words, in order to accept TM as a reliable health care system, its proficiency need to be declared through modern scientific research. One of the major determinants of Persian medicine (PM) which is practically utilized in diseases diagnosis and cure is temperament. Considering the association of depression with the coldness of temperament as well as with the 5-HTTLPR polymorphism, we proposed that the serotonin transporter gene could be a candidate gene contributing to the variation of temperament. To test this hypothesis, in this study, we examined the association of 5HTTLPR polymorphism with the hot/cold status of temperament in the healthy individuals.

The study included 352 healthy men (aged between 20-40 years) referred to the organization of blood transfusion, located in Shiraz city, southern Iran. The participants’ hot/cold status of temperament (warm, temperate and cold) was determined using a standard self-reported scale and to genotype the 5HTTLPR polymorphism, polymerase chain reaction (PCR) was performed. Multinomial logistic regression was used to evaluate 95% CI and ORs for the association of temperament with the 5HTTLPR genotypes. Statistical analysis was performed using the SPSS software with P<0.05 significance level.

In the term of warm temperament, no association with the 5HTTLPR genotypes was observed. However, in respect of cold temperament, our data showed no association with the SS, but the LS genotype; that is, with the reference to the LL, the LS genotype decreased the possibility of coldness rather than temperateness for the temperament (OR=0.471, p=0.040).

Our data revealed the association of temperament with the 5HTTLPR polymorphism which suggest that the temperament may be influenced by the serotonergic system. Further surveys are required to more declare the relation of genetic factors with the temperament.

Type 2 diabetic patients have an abnormally high rate of mortality due to cardiovascular diseases. Given the adverse impact of diabetes on in heart cells and the role of exercise on mitochondrial biogenesis signaling, this study investigated the effect of eight weeks of aerobic exercise on PGC-1a and SIRT-1 gene expression in the myocardium of diabetic male Wistar rats.

This experimental study was conducted on 24 adult male Wistar rats (8 weeks old and weighing 278.26±18.06g), which were randomly assigned to three groups of healthy control (n=8), diabetic control (n=8), and diabetes+aerobic exercise (n=8). The exercise protocol consisted of eight weeks of exercise, three sessions a week, starting with 10 minutes of running at a speed of 10m/s in the first week and ultimately reaching 40 minutes of running at a speed of 18m/s in the eighth week. The changes were analyzed using the one-way analysis of variance and Tukey’s post hoc test.

Significant differences were observed between the groups in terms of body mass (P=0.0001), fasting glucose (P=0.004), serum insulin (P=0.023), and myocardial PGC-1α expression (P=0.031). The post hoc test showed a significant decrease in weight in the diabetic control group (P=0.001) and the diabetic exercise group (P=0.001) compared to the healthy control group. The results also showed a significant increase in the glucose level of the diabetic control group compared to the healthy control group (P=0.008) and a significant decrease in the glucose level of the diabetic exercise group compared to the diabetic control group (P=0.001). A significant decrease was also observed in the insulin level of the diabetic exercise group compared to the diabetic control group (P=0.034). The results of the post hoc test for PGC-1α expression changes showed significantly increased myocardial PGC-1α expression in the diabetic exercise group compared to the diabetic control group (P=0.009). No significant change was detected in the expression of SIRT1 (P=0.075).

The findings suggest that exercise positively affects insulin resistance and weight changes by regulating genes related to mitochondrial biogenesis.

Gestational diabetes mellitus (GDM) is a type of clinical diabetes characterized by insulin resistance and impaired insulin secretion, due to environmental and genetic factors. The high risk of developing T2D in women with GDM and the high risk of developing GDM in women with a family history of T2D suggest that both diseases may have the same genetic basis. Therefore, genes and risk variants associated with the genetic architecture of T2D are being investigated for their effects on development of GDM. In our study, we aimed to investigate ABCC8, TCF7L2, Adiponectin, IRS1 and PPARG genes, which are known as T2D risk genes, in order to understand the genetic basis of GDM in Turkish population.

In our study, 74 pregnant women diagnosed with GDM according to ADA criteria and 49 healthy pregnant women were included. DNA isolations were made from periferal blood cells collected from pregnant women and regions of targeted genes were scanned by PCR-RFLP technique. In biochemical examinations; HOMA-IR, which is an indicator of insulin resistance, was calculated for each individual. The associations of genotypes detected in target gene regions with the disease and their effects on biochemical phenotypes were analyzed by establishing dominant, recessive and additive models and calculating odds ratios. P<0.05 was considered statistically significant in all analyses.

In our study, a statistically significant association was found between R1273R substitution in the ABCC8 gene and GDM under dominant and additive models. No statistically significant correlation was found between the A1369S and e16/-3t→c variants in the ABCC8 gene and the variants in other genes screened and GDM. When genotype-phenotype association data was evaluated, no association was detected between the all scanned variants and fasting blood sugar while a weak correlation was found with e16/-3t→c in ABCC8 gene and fasting insulin (p=0.075) and HOMA-IR (p=0.067).

ABCC8 (R1273R and e16/-3t→c) gene variants may be a risk factor for the development of GDM in the Turkish population.

Antimalarial drug resistance is one of the key challenges that the governments face in the fight against malaria. Molecular surveillance of antimalarial drug resistance supports early detection of how the recommended treatments work. This allows immediate action to reduce any threat and prevent it from spreading. Therefore, the aim of this study was to evaluate the frequency of dihydrofolate reductase (dhfr) mutants in Plasmodium falciparum resistance to primethamine in Iranian malaria patients.

In 2020, 27 patients (21 males and 5 females) with imported P. falciparum cases were studied. The Nested-PCR technique first confirmed the species identity for all samples and then amplified by the Semi-Nested-PCR method in order to detection of single nucleotide polymorphisms (SNPs) in dhfr gene related to pyrimethamine resistance.

All samples in the 18S rRNA gene had species-specific bands for P. falciparum strains. In the sequence analysis of pfdhfr gene amplification after comparison with the standard strain (wild type), 21 patients had a double mutation (C59R+S108N) and 6 patients had a triple mutation (N51I+ C59R+S108N) of pyrimethamine resistance.

The results of this study showed that the susceptibility of P. falciparum to pyrimethamine in the treatment of malaria is significantly reducing. These findings have raised concerns about pyrimethamine resistance in P. falciparum. Due to the high emergence of double and triple mutants related to pyrimethamine resistance, the malaria surveillance and treatment systems in the region should pay more attention to the use of pyrimethamine.