Search

Objective. Myocardial fibrosis is a devastating condition causing millions of deaths yearly. Several factors, such as aging, cause myocardial fibrosis. The Wnt/β-catenin pathway is one of the critical intracellular signaling for the development of cardiac fibrosis. Molecular and cellular mechanism of myocardial fibrosis induced by intensive exercise is not well-understood. The current study evaluates the effects of short- and long-term intensive exercise on the Wnt1 gene expression in a heart left ventricle in an animal model.

Aberrant DNA methylation plays essential roles in the colorectal cancer (CRC) carcinogenesis and has been demonstrated as a promising marker for cancer early detection. In this project, methylation status of the MORT promoter was studied in CRC and their marginal tissues using qMSP assay. Furthermore, we investigated the molecular function of MORT in CRC progression using computational analysis. The results showed a high methylation level of MORT promoter in CRC tissues. By in silico analysis, we found that MORT downregulation could promote the proliferation of CRC cells via sponging of has-miR-574-5p and has-miR-31-5p, and alteration of their targets expression pattern such as MYOCD and FOXP2. In conclusion, based on our results, promoter hypermethylation of MORT might be considered as a potential biomarker for CRC detection. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus is a chronic autoimmune disease that has been associated with human leukocyte antigen G (HLA-G) in previous studies on immunological diseases. This study aimed to investigate the association between three HLA-G gene polymorphisms (rs1632947, rs1233334, and rs371194629) and their impact on HLA-G mRNA expression and soluble HLA-G levels in serum. Genotyping was performed using TaqMan probe PCR. RNA extraction, reverse transcription PCR, and real-time PCR assays were conducted to assess the expression of the HLA-G gene in tissue samples. Soluble HLA-G was measured using enzyme-linked immunosorbent assay in serum. Results show a significant difference in the frequency of the G allele for two 5′-untranslated region (UTR) polymorphisms of the HLA-G gene (rs1632947 and rs1233334) located at positions -964 and -725, respectively, between lupus patients and controls, with p-values of 0.009 and 0.040, respectively. In addition, the study identified the 14 bp insertion allele of the rs371194629 polymorphism located in the 3′ UTR of the gene as a risk factor for lupus, with a p-value of 0.001. Our results also indicate that lupus-related alleles may increase the risk of developing the disease by upregulating the expression of HLA-G and increasing soluble HLA-G levels in serum. The findings of the study suggest that the identified genetic variants may play a role in the development of lupus and could be useful in identifying individuals at risk for the disease. These results are important for advancing our understanding of the genetic basis of lupus and may have implications for the development of new treatments and diagnostic tools for the disease. [ABSTRACT FROM AUTHOR]

Background and Objective(s): Human leukocyte antigen‐G (HLA‐G) is a critical protein in immune regulation and tolerance. Recurrent spontaneous abortion (RSA) is a complex disease influenced by genetic, immune dysfunction, and environmental factors. This study investigates the role of HLA‐G polymorphisms in the development of RSA. Methods: Blood samples were collected from 80 women with RSA and 200 women without a history of RSA. After DNA extraction, PCR was used to sequence the 3′‐UTR region. Allelic and genotypic frequencies were analyzed, and Haploview software was used for haplotype analysis. Results: Individual polymorphisms did not significantly differ between the two groups. However, haplotype analysis revealed significant differences. The UTR‐2 haplotype was more frequent in the RSA group compared to the healthy control group (p = 0.020), suggesting a potential association. Conversely, the UTR‐4 haplotype had a significantly lower frequency in the RSA group (p = 0.041), indicating a protective role against RSA. Conclusions: While individual polymorphisms did not differ significantly, haplotype analysis identified significant associations with RSA. These findings provide valuable insights into the genetic basis of the disease and may contribute to the development of new treatments and diagnostic tools. [ABSTRACT FROM AUTHOR]

Background: People with autism frequently exhibit poor social skills, communication difficulties, and repetitive and stereotyped behaviors. MicroRNAs (miRNAs) are potential and promised targets in developing of new treatment strategies for autism. This study aimed to assess the relative expression of miR-124a, miR-34a-3p, miR-545-3p, miR-153, and BDNF in the blood samples of autistic children. Methods: The children autism rating scale (CARS) was used to determine the severity of autism and to confirm the diagnosis. Blood samples were obtained from 50 patients and 40 age-/sex-matched healthy controls. Expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were evaluated using qRT-PCR. Pearson's correlation coefficient and regression analysis were used to check correlations between relative expressions of the miRNAs and BDNF. Biomarker potencies were assessed by ROC curve analysis. Results: qRT-PCR analysis showed that the relative expressions of miR-545-3p, miR-34a-3p, miR-124a, and BDNF were significantly higher in the patients' group than the healthy controls. However, the relative expression of miR-153 was significantly lower in the case group than the control group. The relative expression of miR-124a was positively correlated with those of miR-545-3p and BDNF among the patients group. Also, the relative expressions of miR-545-3p and BDNF were positively correlated with each other. The ROC curve data also indicated that miR-124a, miR-34a-3p, miR-545-3p, miR-153, and BDNF could be possible diagnostic biomarker for CARS diagnosis (AUC=0.8328, AUC=0.8354, AUC=0.6727, AUC=0.8518 and AUC=0.8214, respectively). Conclusions: Deregulation of miR-124a, miR-454-3p and BDNF might be considered as potential biomarkers for severity of autism. [ABSTRACT FROM AUTHOR]

Background: Pro-inflammatory cytokines play critical roles in cancer pathobiology and have been considered potential targets for cancer management and therapy. Understanding the impact of cancer therapeutics such as 5-fluorouracil (5-FU) on their expression might shed light on development of novel combinational therapies. This study aimed to encapsulate 5-FU into PLGA and evaluate their effects on the expression of pro-inflammatory genes IL-9, IL-17-A, IL-23, and IFN-γ in the HT-29 cells. Methods: PLGA-5-FU NPs were constructed and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The cytotoxicity was evaluated by MTT test and, the IC50 was identified. HT-29 cells were treated with different concentrations of the PLGA-5-FU NPs for 48 hours and, gene expression levels were analyzed by qRT-PCR. Results: DLS and AFM analysis revealed that the prepared PLGA-5-FU NPs were negatively charged spherical-shaped particles with a mean size of 215.9 ± 43.3 nm. PLGA-5-FU NPs impacted the viability of HT-29 cells in a dose- and time-dependent manner. The qRT-PCR results revealed a dosedependent decrease in the expression of IL-9, IL-17A, IL-23 and IFN-γ genes, and their expressions were significantly different in both 10 and 20 μg/mL treated groups compared to the control. However, although the treatment of HT-29 cells with 20 μg/mL free 5-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group. Conclusions: PLGA-5-FU NPs significantly suppressed expression of the IL-9, IL-17A, IL-23 and IFN-γ genes, and the encapsulation of 5-FU into PLGA improved considerably impact of the 5-FU on the HT-29 cells. [ABSTRACT FROM AUTHOR]

Background: Inflammation contributes to cancer pathobiology through different mechanisms. Higher levels of pro-inflammatory cytokines can lead to hyperinflammation and promote cancer development and metastasis. For cancer treatment, Doxorubicin (DOX) can be encapsulated into the poly-lactic-glycolic acid (PLGA) nanoparticles. This study aimed to investigate the impact of doxorubicin-loaded PLGA nanoparticles (DOX-PLGA NP) on the expression of pro-inflammatory genes TNF-α, IL-6, iNOS, and IL-1β in the MCF-7 cells. Methods: The DOX-PLGA NP was prepared by loading doxorubicin into PLGA and characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM). The cytotoxic effect of the nanoparticles was determined by the MTT assay, and their impacts on the expression of pro-inflammatory genes were assessed by qRT-PCR. Results: The encapsulation efficiency and loading capacity were 60±1.5 and 1.13±0.21 percent, respectively. The zeta potential and mean DOX-PLGA nanoparticle size were -18±0.550 mV and 172±55.6 nm, respectively. The 50% inhibitory concentration (IC50) of the DOX-PLGA NP on MCF-7 cell viability was 24.55 μg/mL after 72 hours of treatment. The qRT-PCR results revealed that the 20 μg/mL concentration of the DOX-PLGA NP significantly suppressed the expression of the pro-inflammatory genes TNF-α, IL-6, iNOS, and IL-1β compared to DOX alone (20 μg/mL). Additionally, the suppression effect of DOX-PLGA NP on the expression of these pro-inflammatory genes was dose-dependent. Conclusion: These results show that DOX-PLGA NP efficiently suppressed the expression of proinflammatory genes. Furthermore, encapsulation of DOX into PLGA nanoparticles significantly improved the effectiveness of DOX in suppressing pro-inflammatory genes in MCF-7 breast cancer cells. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is characterized by abnormal increase of Aβ peptide which is likely as the result of imbalanced homeostasis of its production and clearance mechanisms. Here, we briefly review that the uncleaned extracellular Aβ peptides are loaded into presynaptic neurons. The Aβ oligomers desperately affect pre- and post-synapse neuron activity and turn into plaques inside the presynaptic neurons over the time passes. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease that occurs with aging. In its late phases, it is determined by the loss of chondrocytes and the breakdown of the extracellular matrix, resulting in pain and functional impairment. Interleukin-1 beta (IL-1ß) is increased in the injured joints and contributes to the OA pathobiology by inducing chondrocyte apoptosis and up-regulation of matrix metalloproteinases (MMPs). Here, we aimed to understand whether minocycline could protect chondrocytes against the IL-1ß-induced effects. The human C28/I2 chondrocyte cell line was treated with IL-1ß or IL-1ß plus minocycline. Cell viability/toxicity, cell cycle progression, and apoptosis were assessed with MMT assay and flow cytometry. Expression of apoptotic genes and MMPs were evaluated with qRT-PCR and western blotting. IL-1ß showed a significant cytotoxic effect on the C28/I2 chondrocyte cells. The minocycline effective concentration (EC50) significantly protected the C28/I2 cells against the IL-1ß-induced cytotoxic effect. Besides, minocycline effectively lowered IL-1ß-induced sub-G1 cell population increase, indicating the minocycline anti-apoptotic effect. When assessed by real-time PCR and western blotting, the minocycline treatment group showed an elevated level of Bcl-2 and a significant decrease in the mRNA and protein expression of the apoptotic markers Bax and Caspase-3 and Matrix metalloproteinases (MMPs) such as MMP-3 and MMP-13. In conclusion, IL-1ß promotes OA by inducing chondrocyte death and MMPs overexpression. Treatment with minocycline reduces these effects and decreases the production of apoptotic factors as well as the MMP-3 and MMP-13. Minocycline might be considered as an anti-IL-1ß therapeutic supplement in the treatment of osteoarthritis. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent malignancy and the leading cause of cancer-related death in women. Breast cancer is still an extremely difficult cancer to treat due to its significant metastasis. Mis-regulation of Notch signaling components such as Notch receptors/ligands and their interaction in breast cancer sparks tumor initiation, maintenance, and progression through induction of abnormal tumorigenesis while modulating vascular integrity, drug resistance, invasion, and migration. Numerous studies have shown that non-coding RNAs can regulate Notch signaling and accordingly impact breast cancer pathobiology. MiRNAs could regulate Notch signaling components directly or indirectly via sponging or suppressing other genes involved in the pathway. Further, lncRNAs interact with miRNAs and mRNAs, and lncRNA-miRNA-mRNA interaction networks function as substantial mediators in various pathways, including the Notch signaling pathway. Also, by targeting and sponging other genes, circRNAs could induce tumorigenic properties via the Notch signaling pathway. Due to the intricacy of human physiology, it is challenging for standard drugs to be effective, and cancer cells can develop resistance to treatment and have a significant self-renewal capacity. Moreover, because non-specific Notch signaling intervention targets both tumor cells and immune cells, it may have the reverse effect of regulating the formation of tumors. Thus, an in-depth understanding of the mechanisms could be useful in diagnosis, prognosis, and the development of novel medications that specifically target Notch signaling, improving the efficacy of cancer immunotherapy in the treatment of breast cancer. This review will discuss and clarify the mechanisms by which miRNAs, lncRNAs, and circRNAs affect the Notch signaling pathway leading to BC development. [ABSTRACT FROM AUTHOR]

Radiotherapy (RT) has been commonly applied to treat advanced local cancers. In radiation therapy, high doses of radiation are utilized to trigger cell death. Radiation often leads to DNA double-strand breakages (DSB), which causes the activation of downstream genes including those for non-coding RNAs (ncRNA) such as long non-coding and RNAsmicro RNAs. The consequence of RT significantly relies on the radiosensitivity of cancer cells, which is affected by multiple factors, including some proteins and cellular processes. Activation of these genes can cause cell cytotoxicity and indirectly damages the cells. Recent studies have shown that non-coding RNAs can play as radiosensitivity or radioinhibitory regulators in cancers by mechanisms such as cell cycle arrest or affecting the DNA damage repair systems. ncRNAs are also known to function as tumor suppressor genes or oncogenes in colorectal cancer and therefore are considered potential diagnostic biomarkers in disease detection. For example, the investigations have shown that miR-29a and miR-224 can be informative biomarkers for early detection or screening of CRC via a noninvasive method such as liquid biopsy. Here, we discuss ncRNAs involved in the radioresistance and radiosensitivity of CRC and highlight their predictive clinical value in response to RT. Accordingly, this review represents a principal guide in the context of three major types of ncRNAs with potential roles in the pathway of radiosensitivity and radioresistance, including miRNAs, lncRNAs, and circRNAs which can be considered a precious archivement in organizing additional studies and broadening views in this area. Our findings can also assist radiotherapists in predicting CRC patients' response and, therefore, prognosis to radiation therapy, although, to achieve our goals in the clinic, we certainly need further studies. [ABSTRACT FROM AUTHOR]