Bioimpacts最新文献

Introduction: Computational studies were performed to investigate the unknown status of endosomal and cell surface receptors in SARS-CoV-2 infection. The interactions between Toll-like receptors (TLRs)- 4/7/8/9 or ACE2 receptor and different SARS-CoV-2 variants were investigated.

Methods: The RNA motifs for TLR7, TLR8 and a CpG motif for TLR9 were analyzed in different variants. Molecular docking and molecular dynamics (MD) simulations were performed to investigate receptor-ligand interactions.

Results: The number of motifs recognized by TLR7/8/9 in the Alpha, Delta and Iranian variants was lower than in the wild type (WT). Docking analysis revealed that the Alpha, Delta and some Iranian spike variants had a higher affinity for ACE2 and TLR4 than the WT, which may account for their higher transmission rate. The MD simulation also showed differences in stability and structure size between the variants and the WT, indicating potential variations in viral load.

Conclusion: It appears that Alpha and some Iranian isolates are the variants of concern due to their higher transmissibility and rapid spread. The Delta mutant is also a variant of concern, not only because of its closer interaction with ACE2, but also with TLR4. Our results emphasize the importance of ACE2 and TLR4, rather than endosomal TLRs, in mediating the effects of different viral mutations and suggest their potential therapeutic applications.

Introduction: The PI3K/AKT/mTOR signaling pathway plays a significant role in the development of T-cell acute lymphoblastic leukemia (T-ALL). Rapamycin is a potential therapeutic strategy for hematological malignancies due to its ability to suppress mTOR activity. Additionally, microRNAs (miRNAs) have emerged as key regulators in T-ALL pathophysiology and treatment. This study aimed to investigate the combined effects of rapamycin and miRNAs in inhibiting the PI3K/AKT/mTOR pathway in T-ALL cells.

Methods: Bioinformatic algorithms were used to find miRNAs that inhibit the PI3K/AKT/mTOR pathway. Twenty-five bone marrow samples were collected from T-ALL patients, alongside five control bone marrow samples from non-leukemia patients. The Jurkat cell line was chosen as a representative model for T-ALL. Gene and miRNA expression levels were assessed using quantitative real-time PCR (qRT-PCR). Two miRNAs exhibiting down-regulation in both clinical samples and Jurkat cells were transfected to the Jurkat cell line to investigate their impact on target gene expression. Furthermore, in order to evaluate the potential of combination therapy involving miRNAs and rapamycin, apoptosis and cell cycle assays were carried out.

Results: Six miRNAs (miR-3143, miR-3182, miR-99a/100, miR-155, miR-576-5p, and miR-501- 3p) were predicted as inhibitors of PI3K/AKT/mTOR pathway. The expression analysis of both clinical samples and the Jurkat cell line revealed a simultaneous downregulation of miR-3143 and miR-3182. Transfection investigation demonstrated that the exogenous overexpression of miR-3143 and miR-3182 can effectively inhibit PI3K/AKT/mTOR signaling in the Jurkat cell line. Moreover, when used as a dual inhibitor along with rapamycin, miR-3143 and miR-3182 significantly increased apoptosis and caused cell cycle arrest in the Jurkat cell line.

Conclusion: These preliminary results highlight the potential for improving T-ALL treatment through multi-targeted therapeutic strategies involving rapamycin and miR-3143/miR-3182.

Introduction: Glioblastoma (GBM), which is a heterogeneous and aggressive type of brain tumor, is known for its poor survival outcomes. The treatment of GBM remains challenging primarily due to the drug resistance to the current standard therapeutic option, temozolomide (TMZ). Researchers are currently focusing on developing an appropriate alternative combinatorial therapeutic to enhance treatment outcomes. D-limonene (DL) is a monoterpene derived from citrus fruit. This study aims to assess the impact of combining DL with TMZ and explore its potential mechanism of action in U87MG and LN229 GBM cells.

Methods: The effects of the combined treatment of DL and TMZ were assessed on various cellular aspects, including cell viability, anchorage-independent cell growth, and DNA damage. Furthermore, the influence of this combination on cell cycle progression, cell migration, and cell death was also investigated.

Results: The combination of DL+TMZ demonstrated a synergistic effect, resulting in reduced cell proliferation and suppressing the colony formation ability of a single cell. Treatment with DL and TMZ arrested the cells in G0/G1 phase. Furthermore, the DL+TMZ combination induced apoptosis by upregulating the expression of Bax, and Caspase (CASP)-3, while reducing the expression of the Bcl-2 gene in GBM cells. In addition, the combined treatment of DL+TMZ significantly decreased the expression of matrix metalloproteinase (MMP)-2 and MMP-9, expression, indicating inhibition of cell migration in GBM cells.

Conclusion: In conclusion, the combination of DL and TMZ demonstrated a synergistic effect in reducing cell proliferation, suppressing colony formation, inducing apoptosis, and inhibiting cell migration in GBM cells. These findings suggest the potential of DL+TMZ combination therapy as an effective treatment for GBM.

Introduction: Radiofrequency electromagnetic radiation (RF-EMR) and extremely low-frequency electromagnetic fields (ELF-EMF) have emerged as noteworthy sources of environmental pollution in the contemporary era. The potential biological impacts of RF-EMR and ELF-EMF exposure on human organs, particularly the central nervous system (CNS), have garnered considerable attention in numerous research studies.

Methods: This article presents a comprehensive yet summarized review of the research on the explicit/implicit effects of RF-EMR and ELF-EMF exposure on CNS performance.

Results: Exposure to RF-EMR can potentially exert adverse effects on the performance of CNS by inducing changes in the permeability of the blood-brain barrier (BBB), neurotransmitter levels, calcium channel regulation, myelin protein structure, the antioxidant defense system, and metabolic processes. However, it is noteworthy that certain reports have suggested that RF-EMR exposure may confer cognitive benefits for various conditions and disorders. ELF-EMF exposure has been associated with the enhancement of CNS performance, marked by improved memory retention, enhanced learning ability, and potential mitigation of neurodegenerative diseases. Nevertheless, it is essential to acknowledge that ELF-EMF exposure has also been linked to the induction of anxiety states, oxidative stress, and alterations in hormonal regulation. Moreover, ELF-EMR exposure alters hippocampal function, notch signaling pathways, the antioxidant defense system, and synaptic activities.

Conclusion: The RF-EMR and ELF-EMF exposures exhibit both beneficial and adverse effects. Nevertheless, the precise conditions and circumstances under which detrimental or beneficial effects manifest (either individually or simultaneously) remain uncertain.

Introduction: The microfluidic device is highly optimized to remove oocytes from the cumulus-corona cell mass surrounding them. Additionally, it effectively captures and immobilizes the oocytes, aiding in assessing their quality and facilitating the injection of sperm into the oocyte. In this study, a novel microfluidic chip was designed and manufactured using conventional soft lithography methods.

Methods: This research proposes the utilization of a microfluidic chip as a substitute for the conventional manual procedures involved in oocyte denudation, trapping, and immobilization. The microfluidic chip was modeled and simulated using COMSOL Multiphysics® 5.2 software to optimize and enhance its design and performance. The microfluidic chip was fabricated using conventional injection molding techniques on a polydimethylsiloxane substrate by employing soft lithography methods.

Results: A hydrostatic force was applied to guide the oocyte through predetermined pathways to eliminate the cumulus cells surrounding the oocyte. The oocyte was subsequently confined within the designated trap region by utilizing hydraulic resistance along the paths and immobilized by applying vacuum force.

Conclusion: The application of this chip necessitates a lower level of operator expertise compared to enzymatic and mechanical techniques. Moreover, it is feasible to continuously monitor the oocyte's state throughout the procedure. There is a reduced need for cultural media compared to more standard approaches.

Introduction: High metastasis, resistance to common treatments, and high mortality rate, has made triple-negative breast cancer (TNBC) to be the most invasive type of breast cancer. High telomerase activity and mitochondrial biogenesis are involved in breast cancer tumorigenesis. The catalytic subunit of telomerase, telomerase reverse transcriptase (hTERT), plays a role in telomere lengthening and extra-biological functions such as gene expression, mitochondria function, and apoptosis. In this study, it has been aimed to evaluate intrinsic-, extrinsic-apoptosis and DNMT3a and TET2 expression following the inhibition of telomerase and mitochondria respiration in TNBC cell lines.

Methods: TNBC cells were treated with IC₅₀ levels of BIBR1532, tigecycline, and also their combination. Then, telomere length, and DNMT3a, TET2, and hTERT expression were evaluated. Finally, apoptosis rate, apoptosis-related proteins, and genes were analyzed.

Results: The present results showed that IC₅₀ level of telomerase and inhibition of mitochondria respiration induced apoptosis but did not leave any significant effect on telomere length. The results also indicated that telomerase inhibition induced extrinsic-apoptosis in MDA-MB-231 and caused intrinsic- apoptosis in MDA-MB-468 cells. Furthermore, it was found that the expression of p53 decreased and was ineffective in cell apoptosis. The expressions of DNMT3a and TET2 increased in cells. In addition, combination treatment was better than BIBR1532 and tigecycline alone.

Conclusion: The inhibition of telomerase and mitochondria respiration caused intrinsic- and extrinsic- apoptosis and increased DNMT3a and TET2 expression and it could be utilized in breast cancer treatment.