Regulation and Functions of α6-Integrin (CD49f) in Cancer Biology.

Over the past decades, our knowledge of integrins has evolved from being understood as simple cell surface adhesion molecules to receptors that have a complex range of intracellular and extracellular functions, such as delivering chemical and mechanical signals to cells. Consequently, they actively control cellular proliferation, differentiation, and apoptosis. Dysregulation of integrin signaling is a major factor in the development and progression of many tumors. Many reviews have covered the broader integrin family in molecular and cellular studies and its roles in diseases. Nevertheless, further understanding of the mechanisms specific to an individual subunit of different heterodimers is more useful. Thus, we describe the current understanding of and exploratory investigations on the α6-integrin subunit (CD49f, VLA6; encoded by the gene itga6) in normal and cancer cells. The roles of ITGA6 in cell adhesion, stemness, metastasis, angiogenesis, and drug resistance, and as a diagnosis biomarker, are discussed. The role of ITGA6 differs based on several features, such as cell background, cancer type, and post-transcriptional alterations. In addition, exosomal ITGA6 also implies metastatic organotropism. The importance of ITGA6 in the progression of a number of cancers, including hematological malignancies, suggests its potential usage as a novel prognostic or diagnostic marker and useful therapeutic target for better clinical outcomes.

Kaempferol-loaded bioactive glass-based scaffold for bone tissue engineering: in vitro and in vivo evaluation.

Due to the increasing prevalence of bone disorders among people especially in average age, the future of treatments for osseous abnormalities has been illuminated by scaffold-based bone tissue engineering. In this study, in vitro and in vivo properties of 58S bioactive glass-based scaffolds for bone tissue engineering (bare (B.SC), Zein-coated (C.SC), and Zein-coated containing Kaempferol (KC.SC)) were evaluated. This is a follow-up study on our previously published paper, where we synthesized 58S bioactive glass-based scaffolds coated with Kaempferol-loaded Zein biopolymer, and characterized from mostly engineering points of view to find the optimum composition. For this aim, in vitro assessments were done to evaluate the osteogenic capacity and biological features of the scaffolds. In the in vivo section, all types of scaffolds with/without bone marrow-derived stem cells (BMSC) were implanted into rat calvaria bone defects, and potential of bone healing was assessed using imaging, staining, and histomorphometric analyses. It was shown that, Zein-coating covered surface cracks leading to better mechanical properties without negative effect on bioactivity and cell attachment. Also, BMSC differentiation proved that the presence of Kaempferol caused higher calcium deposition, increased alkaline phosphatase activity, bone-specific gene upregulation in vitro. Further, in vivo study confirmed positive effect of BMSC-loaded KC.SC on significant new bone formation resulting in complete bone regeneration. Combining physical properties of coated scaffolds with the osteogenic effect of Kaempferol and BMSCs could represent a new strategy for bone regeneration and provide a more effective approach to repairing critical-sized bone defects.

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies.

Background: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). Methods: We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. Results: A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. Conclusion: This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.

Application of Nanotechnology in Targeting of Cancer Stem Cells: A Review.

Cancer is increasingly apparent as a systems-level, network happening. The central tendency of malignant alteration can be described as a two-phase procedure, where an initial increase of network plasticity is followed by reducing plasticity at late stages of tumor improvement. Cancer stem cells (CSCs) are cancer cells that take characteristics associated with normal stem cells. Cancer therapy has been based on the concept that most of the cancer cells have a similar ability to separate metastasise and kill the host. In this review, we addressed the use of nanotechnology in the treatment of cancer stem cells.