Elderberry diet enhances motor performance and reduces neuroinflammation-induced cell death in cerebellar ataxia rat models.

Cerebellar ataxia (CA) is a condition in which cerebellar dysfunction results in movement disorders such as dysmetria, synergy and dysdiadochokinesia. This study investigates the therapeutic effects of elderberry (EB) diet on the 3-acetylpyridine-induced (3-AP) CA rat model. First, CA rat models were generated by 3-AP administration followed by elderberry diet treatment containing 2 % EB for 8 consecutive weeks. Motor performance, electromyographic activity and gene expression were then evaluated. The number of Purkinje neurons were evaluated by stereological methods. Immunohistochemistry for the microgliosis, astrogliosis and apoptosis marker caspase-3 was also performed. In addition, the morphology of microglia and astrocytes was assessed using the Sholl analysis method. The results showed that EB diet administration in a 3-AP ataxia model improved motor coordination, locomotor activity and neuro-muscular function, prevented Purkinje neurons degeneration, increased microglia and astrocyte complexity and reduced cell soma size. Moreover, EB diet administration decreased apoptosis in cerebellum of 3-AP ataxic model. In addition, elderberry diet treatment decreased the expression of inflammatory, apoptotic and necroptotic genes and increased the expression of antioxidant-related genes. The results suggest that the EB diet attenuates 3-AP-induced neuroinflammation leading to cell death and improves motor performance. Thus, the EB diet could be used as a therapeutic procedure for CA due to its neuroprotective effects.

MicroRNA-26 and Related Osteogenic Target Genes Could Play Pivotal Roles in Photobiomodulation and Adipose-Derived Stem Cells-Based Healing of Critical Size Foot Defects in the Rat Model.

Objective: In this study, we aimed to explore the role of MicroRNA-26 in photobiomodulation (PBM)- and adipose-derived stem cell (ADS)-based healing of critical-sized foot fractures in a rat model. Background: PBM and ADS treatments are relatively invasive methods for treating bone defects. Specific and oriented cellular and molecular functions can be induced by applying an appropriate type of PBM and ADS treatment. Methods: A critical size foot defect (CSFD) is induced in femoral bones of 24 rats. Then, a human demineralized bone matrix scaffold (hDBMS) was engrafted into all CSFDs. The rats were randomly allocated into four groups (n = 6): (1) control (hDBMS); (2) hDBMS+human ADSs (hADSs), hADSs engrafted into CSFDs; (3) hDBMS+PBM, CSFD exposed to PBM (810 nm wavelength, 1.2 J/cm2 energy density); and (4) hDBMS+(hADSs+PBM), hADSs implanted into the CSFD and then exposed to PBM. At 42 days after CSFD induction, the rats were killed, and the left CSFD was removed for mechanical compression tests and the right CSFD was removed for molecular and histological studies. Results: The results indicate that miRNA-26a, BMP, SMAD, RUNX, and OSTREX had higher expression in the treated groups than in the control group. Further, the biomechanical and histological properties of CSFDs in treated groups were improved compared with the control group. Correlation tests revealed a positive relationship between microRNA and improved biomechanical and cellular parameters of CSFDs in the rat model. Conclusions: We concluded that the MicroRNA-26 signaling pathway probably plays a significant role in the hADS-, PBM-, and hADS+PBM-based healing of CSFDs in rats. Clinical Trial Registration number: IR.SBMU.MSP.REC.1398.980.

Role of CYP1A1, CYP2D6, and NOS3 gene polymorphisms in idiopathic recurrent pregnancy loss in the Iranian Azeri population: A case-control study.

Background: It is estimated that 1-5% of couples suffer from recurrent pregnancy loss (RPL). Recent studies have shown the effects of gene polymorphisms in RPL. Objective: The aim of this study was to evaluate 3 gene polymorphisms including rs1048943 of CYP1A1, rs28371725 of CYP2D6, and rs7830 of NOS3 in idiopathic RPL to identify their association with RPL. Materials and Methods: Blood samples were collected from 136 women with at least 2 consecutive idiopathic miscarriages (case group) and 136 women with no history of miscarriage and at least one successful pregnancy (control group) from the Iranian Azeri population. This study was carried out between April 2018-April 2020. Amplification-refractory mutation system polymerase chain reaction was used for the rs7830, rs1048943 and rs28371725 polymorphisms in order to genotype each extracted genomic DNA sample. After that, Chi-square, Fisher's exact test and logistic regression were used to investigate whether each of these polymorphisms is associated with RPL. Results: Among these polymorphisms, only rs1048943 of CYP1A1 showed a statistically significant association with RPL in the Iranian Azeri women studied. Conclusion: Our results suggest that CYP1A1 gene polymorphisms might be associated with a reduced risk of RPL. Further studies in other populations and in the same population with a larger sample size, as well as functional genomics analyses such as gene expression analyses or epigenetic studies are required to validate our results.

miRNA-binding site polymorphism in IL-15RA gene in rheumatoid arthritis and systemic lupus erythematosus: correlation with disease risk and clinical characteristics.

INTRODUCTION/OBJECTIVES: MiRSNPs may interfere with mRNA stability through effects on microRNAs (miRNAs)-mRNA interactions via direct changes in miRNA binding site or effect on the secondary structure of this region and changes in accessibility of this region to miRNAs. Studies have confirmed that an elevated level of interleukin-15 receptor alpha (IL-15RA) has an important role in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In the present study, for the first time, we aimed to evaluate the possible correlation between a miRSNP, rs2296135, in IL-15RA gene with the risk of SLE and RA. METHODS: In this case-control study, 100 SLE patients, 100 RA patients, and 110 healthy participants were enrolled to assess rs2296135 genotypes with real-time PCR high-resolution melting method. RESULTS: According to our findings, AA genotype and A allele of rs2296135 were considerably associated with enhanced risk of RA (for AA genotype, OR = 2.29; 95% CI [1.06-5.02]; for A allele, OR = 1.65; 95% CI [1.10-2.48]). However, this common variant was not significantly correlated with SLE risk in population under study. Stratification analysis in the RA group verified that patients with the A allele had considerably higher serum concentrations of C-reactive protein (CRP) (P < 0.001). In SLE subjects, the frequency of arthritis (P: 0.021) and renal involvement (P: 0.025) in patients with A allele was significantly higher than in other SLE individuals. CONCLUSION: The current study proposes a substantial association between rs2296135 polymorphism in IL-15RA gene with augmented risk of RA and some clinical characteristics in RA and SLE patients.

The effect of extremely low frequency electromagnetic fields following on upregulation of miR-21 and miR-29 in gastric cancer cell line.

AIM: Extremely low frequency electromagnetic fields affect miRNAs expression in cancer cell. In this study, electromagnetic fields exposed to low frequency were used to compare miR-21 and miR-29 expressions in a gastric cancer cell line. BACKGROUND: It has been recently suggested that the low frequency electromagnetic fields probably function as a treatment for cancers. METHODS: A cultured cell line of gastric cancer was exposed to an electromagnetic radiation system. The cell line was assigned to 4 groups under continuous and discontinuous radiations of 0.25 and 2.5 ml Tesla field strength. Then, the groups were compared with a non-radiation control group. Later, RNA extraction and cDNA synthesis were prepared for miR-21 and miR-29. Real Time PCR method was used to determine how expressions of these two microRNAs differ. Finally, the results were statistically analyzed. RESULTS: The percentage of cell viability in the electromagnetic field radiation experienced a significant decrease compared to that of the control group. In addition, expression of miRNA-21 and miRNA-29 had a significant increase as the strength of the electromagnetic field radiations was on an upward trend. Similarly, the percentage of cell viability saw a significant decline in the upregulation of miRNA-21 and miRNA-29 regardless of radiation types. CONCLUSION: Findings of this study showed the therapeutic effect of low frequency electromagnetic fields on the gastric cancer cell line. They also indicated that novel biomarkers (miRNA-21 and miRNA-29) could be proposed as potential treatments of gastric cancer, but the results are required to be well established by future studies.

Plasma Cytokines Profile in Subjects with Alzheimer's Disease: Interleukin 1 Alpha as a Candidate for Target Therapy.

Background: Testicular function depends on temperature, and it has been shown that scrotal hyperthermia causes a sharp decrease in sperm parameters due to oxidative stress. In recent years, the use of natural materials from the plant and nanoparticles has attracted much attention. Therefore, the present study aimed to investigate the effect of curcumin and Fe2O3 nanoparticles on sperm parameters in rats. Materials and Methods: After preparing the rats, they were placed in a hot water bath at 43°C for 30 minutes for six consecutive days. The 48 rats were then divided into eight groups. A concentration of 0.03 mg/kg body weight magnetic Fe2O3 nanoparticles and curcumin at the concentration of 0.02 mg/kg body weight were used. After killing animals, the semen parameters such as viability, concentration, motility, and morphology of sperm were studied. Results: Significant differences were observed in all groups of rats in terms of semen parameters (P<0.001). The results showed a positive effect of curcumin on improving semen parameters in scrotal hyperthermia rats and a negative and toxic effect of Fe2O3 magnetic nanoparticles. However, significant improvement in sperm parameters was observed when Fe2O3 magnetic nanoparticles were given to rats along with curcumin. Conclusion: Curcumin has a positive and significant effect on improving sperm parameters in scrotal hyperthermia conditions. Fe2O3 magnetic nanoparticles, if co-administered with curcumin, can significantly improve sperm parameters. In this regard, green synthesis of nanoparticles and concomitant administration of antioxidants such as curcumin in scrotal hyperthermia conditions is recommended.

Associations of Single Nucleotide Polymorphism in miR-146a Gene with Susceptibility to Breast Cancer in the Iranian Female.

BACKGROUND: MicroRNAs (miRNAs), short regulatory RNAs, function as negative regulators able to modulate gene expression. Just as other genetic variant, single nucleotide polymorphisms (SNPs) in miRNA genes, may have an impact on their expression and/or maturation and hence leading to different consequences in carcinogenesis. Accordingly, this study aimed to assess the frequency of miR-146a G/C (rs2910164) polymorphism and its association with susceptibility to breast cancer in Iranian women. METHODS: We conducted a case-control study using Tetra ARMS polymerase chain reaction (Tetra ARMS PCR) method in 100 Iranian female participants (50 breast cancer patients and 50 controls). Besides, a number of sequenced samples were chosen to confirm the accuracy of genotyping by Tetra ARMA PCR. SPSS software was utilized for all statistical analyses. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to analyze the association between the SNP frequency and breast cancer. RESULTS: The frequency of genotypes for G/G, G/C, and C/C were 23 (46%), 26 (52%), and 1 (2%) among cases and 15 (30%), 33 (66%), and 2(4%) among controls, respectively. The results generated by the groups did not show any significant correlation between miR-146a G/C (rs2910164) polymorphism and breast cancer, either at genotype or allele levels (P>0.05). F-SNP-based in silico analysis indicated possible modifications in transcriptional regulations induced by miR-146a G/C (rs2910164) variations. CONCLUSION: Overall, our results indicated no correlation between miR-146a G/C (rs2910164) polymorphism and genetic susceptibility to breast cancer in Iranian female populations. However, these findings need to be further confirmed by analyses of a larger number of cases.

Four Single Nucleotide Polymorphisms in INSR, SLC6A14, TAS2R38, and OR2W3 Genes in Association with Idiopathic Infertility in Persian Men.

OBJECTIVE: To analyze and evaluate 4 single nucleotide polymorphisms (SNPs)-T132903C, C109869T, T824C, and T886C- and their correlation to the idiopathic Persian (Iranian) infertile male with oligospermia and azoospermia. STUDY DESIGN: A total of 96 idiopathic infertile male patients and 100 normal fertile men (controls) were included in the study. SNP analysis was performed using Real-Time High Resolution Melt analysis (PCR-HRM). Results were confirmed using PCR-RFLP and DNA sequencing analysis. RESULTS: The frequency of 2 SNPs, T132903C in INSR and C109869T in SLC6A14, were statistically different in the infertile males as compared to the control males (p < 0.02 for T132903C and p < 0.04 for C109869T). The SNP frequency for T824C in OR2W3 and T886C in TAS2R38 were similar in the infertile men and the control group with p values of < 0.2 for the T824C and p < 0.9 for T886C SNPs, respectively. CONCLUSION: Our results indicate a significant correlation between T132903C and C109869T SNPs in the INSR and SLC6A14 genes with idiopathic infertility in Persian males. These SNPs may also play a role in defects in spermatogenesis (oligospermia and azoospermia). Our study on Persian infertile, male patients was surprisingly consistent with what others have reported for the European male population. Such similarity might indicate a solid and crucial involvement of these SNPs in idiopathic male infertility in general.

Association study of six SNPs in PRM1, PRM2 and TNP2 genes in iranian infertile men with idiopathic azoospermia.

BACKGROUND: Histones are replaced by protamines to condensate and package DNA into the sperm head during mammalian spermatogenesis. Protamine genes defects have been reported to cause sperm DNA damage and male infertility. OBJECTIVE: In this study relationship among some protamines genes family SNPs include PRM1 (C321A), PRM2 (C248T) and TNP2 (T1019C), (G1272C), (G del in 1036 and 1046 bp) were studied in 96 idiopathic infertile men with azoospermia or oligospermia and 100 normal control men. MATERIALS AND METHODS: Analysis of SNPs was performed using restriction fragment length polymorphism (PCR-RFLP), single strand conformational polymorphism (PCR-SSCP) and PCR sequencing. RESULTS: No polymorphisms were found for tested SNPs except for PRM1 (C321A) and TNP2 (G1272C) in which frequency of altered AA and GG genotypes were slightly higher in infertile case group. Statistical analysis showed no significant association related to PRM1 (C321A) p=0.805 and TNP2 (G1272C) loci p=0.654. CONCLUSION: These results are consistent with previous studies and indicating that all tested SNPs was not associated with oligospermia and azospermia and idiopatic male infertility in Iranian population.

Study of GT-repeat expansion in Heme oxygenase-1 gene promoter as genetic cause of male infertility.

PURPOSE: The length of GT-repeats polymorphic region in the promoter of human Heme oxygenase-1 gene (HO-1) alters the level of its transcriptional activity in response to oxidative stresses. Decreased level of HO-1 protein in the seminal plasma has been reported to be associated with oligospermia and azoospermia in male infertility. This is the first study to investigate the association between GT-repeats expansion in the promoter of the HO-1 gene and male infertility. METHODS: The frequencies of different GT-repeats alleles in the promoter of HO-1 gene were determined in 100 cases and 100 normal controls using PCR-PAGE, ABI fragment analysis genotyping and sequencing analysis. RESULTS: All alleles were classified into S and L alleles. S alleles were specified as number 0 to 3 with <27 GT-repeats and L alleles were specified as number 4 to 6 with >27 repeats. The L allele frequency was significantly higher among case group (54.5%) than that was obtained in the normal control group (37.5%). Statistical analysis provided a significant relationship between L allele and male infertility (P < 0.001). CONCLUSIONS: This study shows for the first time that GT-repeats expansion in promoter of the HO-1 gene is associated with oligospermia and azoospermia among Iranian infertile cases.