Targeting ferroptosis for leukemia therapy: exploring novel strategies from its mechanisms and role in leukemia based on nanotechnology.

The latest findings in iron metabolism and the newly uncovered process of ferroptosis have paved the way for new potential strategies in anti-leukemia treatments. In the current project, we reviewed and summarized the current role of nanomedicine in the treatment and diagnosis of leukemia through a comparison made between traditional approaches applied in the treatment and diagnosis of leukemia via the existing investigations about the ferroptosis molecular mechanisms involved in various anti-tumor treatments. The application of nanotechnology and other novel technologies may provide a new direction in ferroptosis-driven leukemia therapies. The article explores the potential of targeting ferroptosis, a new form of regulated cell death, as a new therapeutic strategy for leukemia. It discusses the mechanisms of ferroptosis and its role in leukemia and how nanotechnology can enhance the delivery and efficacy of ferroptosis-inducing agents. The article not only highlights the promise of ferroptosis-targeted therapies and nanotechnology in revolutionizing leukemia treatment, but also calls for further research to overcome challenges and fully realize the clinical potential of this innovative approach. Finally, it discusses the challenges and opportunities in clinical applications of ferroptosis.

Combinatorial targeting of telomerase and DNA-PK induces synergistic apoptotic effects against Pre-B acute lymphoblastic leukemia cells.

BACKGROUND: Due to the high demand for novel approaches for leukemia-targeted therapy, this study investigates the impact of DNA-PK inhibitor NU7441 on the sensitivity of pre-B ALL cells to the telomerase inhibitor MST-312. METHODS: The study involved NALM-6 cells treated with MST-312 and NU7441, assessing their viability and metabolic activity using trypan blue and MTT assays. The study also evaluated apoptosis, gene expression changes, and DNA damage using flow cytometry, qRT-PCR, and micronucleus assays. The binding energy of MST-312 in the active site of telomerase was calculated using molecular docking. RESULTS: The study's findings revealed a synergistic decline in both cell viability and metabolic activity in NALM-6 cells when exposed to the combined treatment of MST-312 and NU7441, and this decrease occurred without any adverse effects on healthy PBMC cells. Furthermore, the combination treatment exhibited a significantly higher induction of apoptosis than treatment with MST-312 alone, as observed through flow cytometry assay. qRT-PCR analysis revealed that this enhanced apoptosis was associated with a notable downregulation of Bcl-2 expression and an upregulation of Bax gene expression. Moreover, the combination therapy decreased expression levels of hTERT and c-Myc genes. The micronucleus assay indicated that the combination treatment increased DNA damage in NALM-6 cells. Also, a good conformation between MST-312 and the active site of telomerase was revealed by docking data. CONCLUSIONS: The study suggests that simultaneous inhibition of telomerase and DNA-PK in pre-B ALL presents a novel targeted therapy approach.

Extracellular microvesicles: biologic properties, biogenesis, and applications in leukemia.

Microvesicles are cellular membrane vesicles of which size is limited to 30-1000 nm. Almost all cells release them in response to activation signals and apoptosis. Their ability for intercellular communication and enhancement of potential for information exchange (between them) has attracted much interest. Their content is affected by the content of the mother cell, which can help identify their origin. Furthermore, these particles can change the physiology of the target cells by transferring a set of molecules to them and changing the epigenetics of the cells by transferring DNA and RNA. These changes can be induced in cells close to the mother and distant cells. Significant activities of these microvesicles are known both in physiological and pathologic conditions. In this regard, we have reviewed these small particle elements, their contents, and the way of synthesis. Finally, we discussed their current known roles to reveal more potential applications in leukemia.

Nanotechnology development in surgical applications: recent trends and developments.

This paper gives a detailed analysis of nanotechnology's rising involvement in numerous surgical fields. We investigate the use of nanotechnology in orthopedic surgery, neurosurgery, plastic surgery, surgical oncology, heart surgery, vascular surgery, ophthalmic surgery, thoracic surgery, and minimally invasive surgery. The paper details how nanotechnology helps with arthroplasty, chondrogenesis, tissue regeneration, wound healing, and more. It also discusses the employment of nanomaterials in implant surfaces, bone grafting, and breast implants, among other things. The article also explores various nanotechnology uses, including stem cell-incorporated nano scaffolds, nano-surgery, hemostasis, nerve healing, nanorobots, and diagnostic applications. The ethical and safety implications of using nanotechnology in surgery are also addressed. The future possibilities of nanotechnology are investigated, pointing to a possible route for improved patient outcomes. The essay finishes with a comment on nanotechnology's transformational influence in surgical applications and its promise for future breakthroughs.

Differential Expression of the hTERT Gene in Umbilical Cord-Derived Mesenchymal Stem Cells Cocultured with B Cell Precursor Leukemia Cell Microparticles or CD41+/CD61+ Platelet Microparticles.

Several investigations are being done to increase the short lifetime of mesenchymal stem cells (MSCs). One of the crucial genes involved in the immortalization of MSCs, hTERT (human telomerase reverse transcriptase), is activated in most publications using viral-based techniques. In this work, we investigated the use of platelet-derived (PMPs) and B cell precursor leukemia-derived microparticles as a nonviral method to trigger and compare the expression of the hTERT gene in MSCs. MSCs were extracted from the umbilical cord for the current investigation and identified using a flow cytometry approach and an inverted microscope. The Nalm-6 cell line and platelet concentrate were used to isolate microparticles (MPs). MSCs and MPs were cocultured for 14 days at 25-, 50-, and 100 µg/ml concentrations. qRT-PCR was used to research the expression of the hTERT gene. SPSS 26.0's t test was used to compare the outcomes. After coculture with platelet MPs, MSCs had higher levels of hTERT gene expression than the control group. In contrast, this gene's expression was concurrently decreased in MSCs exposed to MPs generated from Nalm-6. We demonstrated that following 14-day treatment, PMP significantly boosted the hTERT gene expression in MSCs, while the Nalm-6 MPs lowered the gene expression. However, additional studies are necessary due to the stability of hTERT gene expression and the immortalization of MSCs following exposure.

Ofatumumab regimens in chronic lymphocytic leukemia: a meta-analysis.

Ofatumumab's therapeutic impact on patients with chronic lymphocytic leukemia (CLL) has been the subject of increasing clinical research. However, in recent years, no studies have yet provided a pooled assessment of the treatment effect of ofatumumab vs. non-ofatumumab regimens. Therefore, we conducted a progression meta-analysis to evaluate the efficacy of ofatumumab-based treatment in CLL patients using data from clinical studies. Relevant publications from PubMed, Web of Science and ClinicalTrials.gov were searched. The efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The articles reviewed in the mentioned databases and matching the specified keywords were searched until January 2023. The pooled efficacy analysis showed that there was a significant difference in PFS [hazard ratios (HR) = 0.62, 95% confidence interval (CI) = 0.52-0.74] and no significant difference in OS (HR = 0.86, 95% CI = 0.71-1.03) between ofatumumab-based therapy and non-ofatumumab therapy. Our analysis showed the pooled efficacy for PFS was statistically significantly improved with ofatumumab-based treatments for CLL compared with other groups. Also, ofatumumab had no statistically significant improvement in the OS of patients with CLL. Thus, ofatumumab-based therapies for CLL patients could be improved by other combinational-based regimens.