majid tafrihi

Teucrium persicum (T. persicum) is a well-known Iranian endemic plant that grows in the southern regions of Iran. It is used as a tea to treat abdominal pains, hyperlipidemia, and diabetes in traditional Iranian medicine. It has been previously found that the methanolic extract of T. persicum exerts significant cytotoxicity and inhibitory effects on different cancer cells. This study aimed to investigate the effects of ethyl acetate extract of T. persicum on MCF-7 cells. 

The experiments included MTT, DAPI staining, and investigating the expression of BAX and BCL2 genes. The extract had a significant cytotoxic effect on MCF-7 cells, with an IC50 value of 50 µg/ml for 48 hr. 

DAPI staining assays showed that the extract induced morphological changes, chromatin condensation, and nuclear fragmentation. Additionally, the ethyl acetate extract induced the expression of BAX and down-regulated BCL2 genes. 

These findings suggest that T. persicum has strong cytotoxic properties and warrants further investigation.

Ferula gummosa Boiss. is a widely recognized species native to Iran, primarily found in the northern and northeastern regions. It has long been valued for its medicinal properties, particularly in traditional medicine, where its gum is used to treat various gastrointestinal disorders and infections.

However, despite its established benefits, there is a significant research gap regarding its potential anti-cancer properties, specifically against skin cancer cells.

This study aimed to assess the cytotoxic and inhibitory effects of the gum of F. gummosa on the A-375 cell line using several assays, including MTT, clonogenic, acridine orange/ethidium bromide (AO/EtBr) staining, DNA degradation, and in vitro wound-healing experiments.

The findings revealed that the gum exhibited notable cytotoxicity on A-375 cells, achieving a 50% inhibitory concentration (IC 50 ) at 8 µg/mL after 48 hours of treatment (compared to control cells) (P < 0.01). The observed DNA degradation pattern suggested a reduction in cell viability, likely due to apoptosis induction. Microscopic examinations showed nuclear condensation and a significant suppression of colony formation in A-375 cells treated with 8 and 10 μg/mL concentrations of the gum, compared to untreated cells. Additionally, wound-healing assessments demonstrated the gum’s ability to inhibit cell migration in contrast to the untreated group.

These findings suggest that F. gummosa exhibits significant inhibitory effects on melanoma cancer cells, making it a promising candidate for further investigation.

Methylmalonic acidemia (MMA) is a rare autosomal recessive metabolic disorder resulting from a genetic defect in methylmalonyl-CoA mutase (MCM) or a defect in the biosynthesis of its cofactor, adenosyl-cobalamin (AdoCbl). The disease is caused by a mutation in six main genes (MUT, MMAA, MMAB, MMADHC, MMACHC, and MCEE). In this investigation, we estimate MMAdisease gene frequencies globally and report MMA-causative mutations in the Iranian population.

Human gene mutation database (HGMD) has been utilized to estimate MMA-disease gene frequencies. To compile MMA mutations in Iran, we systematically reviewed PubMed, Google Scholar, CIVILICA, Magiran, and SID databases to explore relevant articles in English and Persian.

The frequencies of causative genes among MMA patients at the global level were as follows: MUT (64.14%), MMACHC (17.74%), MMAA (13.48%), MMAB (7.1%), MMADHC (2.9%), and MCEE (0.85%). Until February 11, 2024, 24 MMA mutations had been compiled from the Iranian population; of which 11 mutations (45.8%) had been diagnosed only in Iran and had not been addressed in other populations yet.

Collection and recognition of MMA mutations in the Iranian population can be helpful for early diagnosis and treatment before the onset of neurological manifestations in neonates.

Context: 

Cellular metabolism is a set of controlled biochemical reactions known as metabolic pathways that occur in living organisms in order to sustain life. Cells may use different metabolic pathways and alter metabolism to use more effective processes for survival depending on cellular conditions. Alterations in metabolic pathways can lead to the transformation of normal cells into cancerous cells, leading to cancer initiation and development.

 Proper cellular conditions in terms of pH and the availability of essential nutrients and oxygen are important for the healthy functioning of aerobically respiring human cells. If cells are exposed to stressors such as carcinogens that can induce mutations in the genes involved in metabolic pathways, anaerobic metabolism may be used by cells, turning them into cancerous cells. Cellular conditions that maintain aerobic cellular respiration and mitigate the effects of cellular stressors can improve cells’ resistance to neoplastic transformation.

 This paper explores the key metabolic pathways used by cancer cells as a function of their environmental conditions based on the Warburg effect. In addition, some analyses and studies were conducted on global and regional cancer incidence rates, taking into account changes in lifestyle and dietary patterns.
Results and

 Natural resistance to cancer may be improved when cells grow in healthy conditions at molecular levels, requiring a balanced alkalizing diet and healthy lifestyle, as well as reduced exposure to environmental carcinogens, which are key control factors. In particular, effective nutritional interventions can help normal cells resist metabolic changes underlying cancer development.

Diabetic retinopathy is the most severe diabetic microvascular complication that causes changes in the vessel wall. One of the genes involved in this disease is PON1, which encodes paraoxanase1 protein in liver and kidney. It might regulate inflammatory and microvascular responses to the disease. The rs662 T>C is one of the single nucleotide polymorphisms of this gene that changes glutamine to arginine at position 192.

In this study, 300 samples were collected, including 100 healthy and 100 diabetics without retinopathy, and 100 diabetics retinopathies were studied and their age range was from 30 to 80 years. Then 2.5 ml of blood was collected from all relevant individuals in tubes containing EDTANa2</sub>. This polymorphism was examined by tetra-ARMS PCR.

Results showed that there is no significant correlation between genotypes and alleles related to PON1 and Diabetes (CC genotype: p=0.609; C allele: p=0.228). On the other hand, an association was observed between PON1 and diabetic retinopathy (CT+CC genotype: p<0.001; CT allele: p<0.001). Considering that the Polyphen database examined the changes caused by replacing the amino acid arginine instead of glutamine at position 129 on the protein, it does not consider these changes dangerous and has introduced this polymorphism as benign.

Based on the findings of this study, the rs662 locus could be considered as one of the molecular markers in future research.

Ferula gummosa Boiss is a well-known Iranian endemic plant that has been used in Iranian traditional medicine against various diseases. This study aimed to evaluate the antioxidant and cytotoxic capacity of F. gummosa gum on prostate cancer PC-3 cells. In this study, we evaluated the total phenolic and flavonoid contents, and antioxidant potentials of the gum. The MTT experiment was conducted to assess the cytotoxic potential of the gum on PC-3 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of PC-3 cells. DNA degradation and caspase 3/7 activity evaluations were used to assess apoptosis. The inhibitory effect on the migration of PC-3 cells was examined by in vitro wound-healing experiment. Total phenolic and flavonoid contents, and antioxidant potential of the gum were 9.22 mg of gallic acid equivalent (GAE)/g, 3.6 mg of quercetin equivalents (QE) /g of the extract, and 13 μg/ml, respectively (compared to gallic acid and quercetin, respectively) (p<0.05). The IC50 value was 9.14 µg/ml for 48 hours (compared to non-treated cells) (p<0.01).  The pattern of DNA degradation, and caspase 3/7 activity levels (compared to non-treated cells) (p<0.05) proposed decreased cell viability that may be due to apoptosis induction. Microscopic observations revealed nuclear condensation, a significant increase in the formation of micronuclei, and inhibition of forming colonies (compared to non-treated cells) (p<0.01) in PC-3 cells treated with 8 and 10 μg/ml of the gum. Wound-healing assessment showed the migration suppression potentials of the gum (compared to non-treated cells) (p<0.05). These results indicate that F. gummosa has considerable antioxidant and cytotoxic properties that can make it a good nominee for subsequent investigations.

Medicinal plants contain a high level of antioxidant compounds such as flavonoids, phenolic, carotenoids, and tannins, which can be used to eliminate excess free radicals in the body. This study aimed to determine the total phenolic and flavonoid content and to investigate the antioxidant and antibacterial effects of Berberis integerrima and Graminifolius tragopogon methanolic extracts on some Gram-positive and Gram-negative microorganisms.

In this descriptive-analytical study, methanolic extracts of B. integerrima and G. tragopogon were prepared using 80% methanol. Total phenol and flavonoid contents were determined by Folin–Ciocalteu and aluminum chloride colorimetric methods, respectively. The antioxidant capacity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reducing power methods. The antibacterial activity of the extracts of B. integerrima and G. tragopogon on Escherichia coli, Bacillus subtilis, Listeria monocytogenes, Staphylococcus aureus, and Salmonella typhimurium were determined by the disk diffusion method. Butylated hydroxytoluene and ciprofloxacin were used as positive controls for antioxidant activity and bacterial strains, respectively.

Total phenol and flavonoid compounds in the extracts of B. integerrima and G. tragopogon were 46.90±0.70 and 22.63±0.59 mg gallic acid per gram of extract and 5.61±0.01 and 46.74±0.81 mg quercetin per gram of extract, respectively. The extracts of B. integerrima and G. tragopogon showed significant antibacterial activity. B. subtilis and S. typhimurium showed the highest sensitivity and resistance to the extracts, respectively. Moreover, the extract of B. integerrima had the most potent inhibitory effect on the examined microorganisms.

B. integerrima extract exhibits higher phenolic content, antioxidant properties, and antimicrobial activity than G. tragopogon extract.

Warburg effect is a form of cellular metabolism commonly used by cancer cells, in which, consumption of glucose and production of acidic cell metabolic wastes take place at a considerably higher rate. The effect is well described in the literature, however, the applications for cancer prevention and treatment have not been resolved effectively yet. According to the Warburg effect, anaerobic cellular respiration and the resulting acidic cellular environment are linked to the development of cancerous tumors. But an oxygen-rich environment with optimum alkalinity at the cellular level can result in retaining healthy cells and inhibiting cancer cell growth. As an alternative or complementary solution for cancer treatment based on the Warburg effect, a healthy balanced diet with alkalizing (but not alkaline) properties helps maintain acid-base balance in the body and also provides optimum metabolic rate and sufficient hydration for more effective health improvement. This paper presents a review of the key concepts related to links between cancer and dietary and environmental factors, with the main focus on the Warburg effect and energy metabolisms in cancer cells. In addition, some practical diet-based solutions are summarized that may potentially control cancer by utilizing the reversed Warburg effect by which, optimum pH levels and sufficient oxygenation may be provided at the cellular level.

Trametes versicolor is important for its medicinal rather than nutritional value. Given the various pharmacological activities of this plant, this study aimed to investigate the antioxidant and antimicrobial potential of the aqueous extract of T. versicolor.

In this descriptive-analytical study, an aqueous extract of T. versicolor was prepared. Antioxidant activity, flavonoid content and total phenol were measured by diphenyl picryl hydrazyl (DPPH) and reducing power (RP) methods, aluminum chloride (AlCl3), and Folin-Ciocalteu assays. The antibacterial and antifungal activity of the aqueous extract of T. versicolor on Staphylococcus aureus, Escherichia coli and Fusarium thapsinum was determined by the disk diffusion method. Butylated hydroxytoluene (BHT), ciprofloxacin and amphotericin-B were used as positive controls for antioxidant activity and bacterial and fungal strains, respectively.

Total phenolic content was 27.6±0.38 (mg GAE/g), and total flavonoid content was 4.2±0.04 (mg QE/g). Based on DPPH radical scavenging activity, the extract of T. versicolor showed strong scavenging activity (93.8±1.2 %) with IC50 of 103.9±0.8 μg/mL when compared with the standard BHT (IC50 of 30.0±0.6 μg/mL). In addition, it was observed that increasing the concentration of aqueous extract of turkey tail increased the reducing power of iron. The zone of inhibition around the extract ranged from 13.0±0.65 mm (in F. thapsinum at 75 mg/ml) to 21±0.73 mm (in S. aureus at 300 mg/ml) (P<0.05).

The aqueous extract of  T. versicolor contains a significant amount of phenolic compounds and also has strong antimicrobial and antioxidant properties.

Teucrium persicum, a well-known Iranian endemic plant, has been used to treat various diseases in Iranian traditional medicine.

This study aimed to assess the antioxidant and cytotoxic effects of chloroform and ethyl acetate extracts of T. persicum on cancer cell lines.

The total phenolic and flavonoid contents, as well as the antioxidant potential of chloroform and ethyl acetate extracts were assayed. The GC-MS analysis was used to detect the chemical constituents of these two extracts. The cytotoxicity effects of extracts on two cancer cell lines, PC-3, SW-480, and HEK-293, as normal cell lines were evaluated using the MTT assay.

The average total phenolic contents of chloroform and ethyl acetate extracts were found to be 48 ± 0.2 and 25 ± 0.4, respectively (P < 0.05). The total flavonoid contents of chloroform and ethyl acetate extracts were measured as 34 ± 0.6 and 36 ± 0.6 mg EQ/g of the dried extract, respectively (P < 0.05). The antioxidant potential of chloroform and ethyl acetate extracts were calculated as 2.5 ± 0.013 and 3 ± 0.0023 µg/mL, respectively (P < 0.05). According to the GC-MS analysis, 60 and 61 different bioactive compounds were detected in chloroform and ethyl acetate extracts, respectively. MTT results showed that the SW-480 cell line was more sensitive than PC-3 and HEK-293 cells.

It was concluded that T. persicum had significant antioxidant and cytotoxic properties. Taking our study results into account, cancer inhibiting properties of T. persicum were strongly supported. However, it was recommended that further specific and detailed biochemical and molecular studies should be conducted in order to discover the effective compound(s) and mechanism(s) responsible for producing these effects.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has currently caused a significant pandemic among worldwide populations. The high transmission and mortality rates of the disease necessitate studies for rapid designing and effective vaccine production. This study aims to predict and design a novel multi-epitope vaccine against the SARS-CoV-2 virus using bioinformatics approaches. 

Coronavirus envelope proteins, Open Reading Frame 7b (ORF7b), Open Reading Frame 8 (ORF8), Open Reading Frame 10 (ORF10), and Nonstructural protein 9 (Nsp9) were selected as targets for epitope mapping using Immune Epitope Data Bank (IEDB) and BepiPred 2.0 servers. Also, molecular docking studies were performed to determine the candidate vaccine’s affinity to Toll-Like Receptor (TLR3, TLR4) and Major Histocompatibility Complex (MHC I and MHC II) molecules. Thirteen epitopes were selected to construct the multi-epitope vaccine. 

We found that the constructed peptide has valuable antigenicity, stability, and appropriate half-life. The Ramachandran and ERRAT plots approved the quality of the predicted model after the refinement process. Molecular docking investigations revealed that antibody-mode in the ClusPro 2.0 server showed the lowest binding energy for MHC I, MHC II, TLR3, and TLR4.

The designed vaccine has a good antigenicity and stability and could be a proper vaccine candidate against the Coronavirus Disease 2019 (COVID-19) infectious disease though, in vitro and in vivo experiments are necessary to complete and confirm our results.

Teucrium persicum is an Iranian endemic plant used in Iranian traditional medicine. The total phenolic and total flavonoid contents, and antioxidant potential of the methanolic extract of T. persicum were determined. The MTT test was used to evaluate the inhibitory effect of the extract on the viability of A-375 cells. The clonogenic, micronucleus formation, and acridine orange/ethidium bromide staining methods were used to evaluate the survival and proliferation of A-375 cells. Apoptosis was evaluated by using DNA fragmentation assay and measuring the activity of caspase 3/7. To study the effect of the extract on the migration of A-375 cells, the in vitro wound-healing (scratch) assay was employed. The average total phenolic and flavonoid contents and antioxidant properties of the extract were 6.97±0.011 mg Ellagic acid (EGA)/g, 46.83±0.0019 mg of the ethoxyquin (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline; EQ)/g of dried extract, and 10±0.002 μg/ml, respectively. The IC50 value of the T. persicum methanolic extract was 13 μg/ml for 48 hr. The DNA fragmentation pattern and the activity of caspase3/7 suggested that the reduction of the cell viability may be due to apoptosis induction. Microscopic observations showed nuclear condensation, a considerable increase in micronuclei formation, and inhibition of the colony formation in A-375 cells treated with 7 μg/ml to 15 μg/ml of the extract. Wound-healing assay supported the anti-migration activity of the extract. T. persicum has significant antioxidant and cytotoxic properties. Surely, more detailed molecular and biochemical studies are needed to find the mechanism(s) behind these effects.

Chromosomal aneuploidies are the most chromosomal abnormalities at birth due to maternal meiosis I errors. Pregnancies with autosomal chromosomal aneuploidies that survive are namely trisomies 13 (Patau syndrome), 18 (Edward syndrome), and 21 (Down syndrome), account for 89% of chromosome abnormalities. Quantitative fluorescent polymerase chain reaction (QF-PCR) which amplifies specific DNA sequences called short tandem repeats (STRs), by using fluorescently labeled primers is a rapid technique for prenatal diagnosis of common aneuploidies. In this study, DNA extraction was performed from 100 samples isolated from muscle tissue of aborted fetuses. The analysis was performed by multiplex QF-PCR using a panel of 25 STRs markers for chromosomes X, Y, 13, 18, and 21. Our results showed that 20% of abortions were due to aneuploidy. 53% of mothers who had abortions were aged 26-35 years old and 32% of them were aged 36-45 years old. The analysis of muscle samples of aborted fetuses indicated that 20 samples showed chromosomal aneuploidy. Of the abnormal cases, 10 cases (~50 %) showed trisomy 21 followed by trisomy 18 (7 cases, ~35%), Klinefelter syndrome (2 cases, ~10 %), and showed trisomy X (1 case, ~5 %). Our results indicated that the D21S1414 marker showed the highest rate of heterozygosity in the study population. Besides some limitations of this study such as sample size, these results suggest that one of the causes of these abortions could be maternal age. We concluded that QF-PCR could be a rapid and reliable method to screen prenatal chromosomal aneuploidy and allow appropriate counseling.

E-cadherin is a tumor suppressor protein that plays a crucial role in cell-cell adherens junction and tissue architecture and it is hypothesized to participate in carcinogenesis. It has been shown that a polymorphism in the upstream of the transcription start site of the CDH1 gene affects E-cadherin transcriptional regulation and seems to be associated with a variety of cancers. For the first time, we investigated the association of the rs16260 in the 5'-untranslated region of the CDH1 gene with gastric cancer in Iranian population. Seventy- eight patients with gastric cancer and 72 healthy individuals were included and genotyped for this SNP using the PCR-RFLP method. Our results showed that the frequency of the AA genotype in gastric cancer patients (16 of 78, 20.5%) was higher than healthy individuals (9 of 72, 12.5%), the frequency of the A allele in the patients group was higher than controls (OR=1.231, 95% CI= 0.772-1.962, p-value= 0.383), but statistical analysis revealed the absence of association between AA genotype and gastric cancer risk (OR=1.719, 95% CI= 0.656-4.502, p-value= 0.268). In conclusion, our results suggest that this substitution and the AA genotype have not a major impact on the individual’s susceptibility to gastric cancer, and therefore this SNP may be an ethnicity-dependent risk factor. Further works with larger sample size and including other criteria such as H. pylori infection status are needed for more accuracy.

Microsatellites or simple sequence repeats (SSRs) are very effective molecular markers in population genetics, genome mapping, taxonomic study and other large-scale studies. Variation in number of tandem repeats within microsatellite refers to simple sequence length polymorphism (SSLP); but there are a few studies that are showed SSRs replication slippage may be occurred during in vitro amplification which are produced ‘stutter products’ differing in length from the main products. The purpose of this study is introducing a reliable method to realize SSRs replication slippage. At first, three unique primers designed to amplify SSRs loci in the great gerbil (Rhombomys opimus) by PCR. Crush and soak method used to isolate interesting DNA bands from polyacrylamide gel. PCR products analyzed using by sequencing methods. Our study has been shown that Taq DNA polymerase slipped during microsatellite in vitro amplification which led to insertion or deletion of repeats in sense or antisense DNA strands. It is produced amplified fragments with various lengths in gel electrophoresis showed as ‘stutter bands’. Thus, in population studies by SSRs markers recommend that replication slippage effects and stutter bands have been considered.

E-cadherin protein is a member of cadherin superfamily which expressed mainly at the surface of epithelial cells. Reduced expression of this protein results in cell adhesion weakening, EMT (Epithelial-mesenchymal transition), migration and metastasis of epithelial cancer cells. In traditional medicine, pomegranate (Punica granatum) is used to treat several diseases including diarrhea, heart diseases and blood pressure disorders. In this study, we examined the effect of pomegranate acetone extract on the expression of β-catenin and E-cadherin proteins in PC-3 cancer cells. The results of MTT experiments showed that acetone-derived extract of pomegranate inhibits viability of PC-3 cells, especially in concentrations higher than100 μg/ml. The IC50 value of pomegranate extract was estimated to be 86μg/ml. The results of western blotting experiments showed that concentrations of 20 and 50 μg/ml of pomegranate extract led to 1.5- and 2.2-folds increase in β-catenin and E-cadherin protein levels, respectively. The results of this study suggest that pomegranate fruit may have great potentials in inhibition of cancer cell metastasis.