Studies on Genetic Aberrations in Acute Myeloid Leukemia

Hematopoiesis is the formation of blood cellular components. In mammalian embryonic development, the yolk sac and its vasculature are the source of the first blood cells called hematopoietic stem cells (HSCs) from which all blood cells originate. HSCs are produced by the aorta-gonad-mesonephros region, yolk sac and placenta from where they migrate to the fetal liver, where they expand. Hereafter, HSCs transfer to the bone marrow from where they establish the definitive adult hematopoiesis and reside throughout adulthood. HSCs are responsible for foundation of the adult blood differentiation hierarchy and provide continuous hematopoietic cell production. The major characteristic of HSCs is their self-renewal capacity, i.e., they proliferate to give rise to all different types of blood cells, but the pool of stem cells does not become depleted . HSCs are pluripotent. They generate more committed progenitor cells or other stem cells, i.e., common myeloid and lymphoid progenitor cells (CMPs and CLPs respectively) which differentiate and give rise to the progeny belonging to these two lineages of blood cells. While the lymphoid progenitor cells generate B- and T cells as well as natural killer cells, the myeloid progenitor cells produce the other leukocytes, i.e. granulocytes and monocytes/macrophages, as well as red blood cells (erythrocytes) and platelets (Figure 1). The life span of mature blood cells is relatively short and cell production process is continuous, therefore it demands tight regulation by hematopoietic growth factors. The hematopoietic growth factors are a family of cytokines that interact with specific receptors on hematopoietic cells. These molecules like stem cell factor (SCF) or KIT ligand (KIT-L), granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), and macrophage CSF (M-CSF), regulate the functional activation of the specific cells with which they interact. Hematopoietic growth factors are required for the survival, proliferation, and differentiation of hematopoietic progenitors

A Discursive Tradition Analysis in the Field of Political Islam

The article processing charge was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491192747 and the Open Access Publication Fund of Humboldt-Universität zu Berlin.This article explores the idea of political Islam as a discursive tradition within the context of Iranian Kurdistan. It challenges the prevailing essentialist and universalist approaches commonly used in the analysis of political Islam, advocating for a more adaptable and comprehensive interpretation. By conceptualizing political Islam as a discursive tradition, this study sheds light on the complex interconnections, configurations, and historical contingencies influencing Islamist discourses and movements. The paper argues that political Islam should be examined in relation to other phenomena and discourses, acknowledging its dynamic nature within specific temporal and spatial contexts. Focusing on an influential yet underexplored Islamist discursive tradition in Iranian Kurdistan during the 1970s and 1980s, the research acknowledges the hybrid nature of Islamist discourses, drawing from diverse traditions to fulfill particular objectives. In particular, it explores the perspectives of Ahmad Moftizadeh, a Sunni Kurdish Islamist and the founder of the Maktab Quran (MQ). This study investigates Moftizadeh’s views on the Islamic government, positioning it within the framework of discursive tradition. It analyzes his core categories and inquiries within Islamist thought, notably emphasizing Moftizadeh’s alignment of the Islamic government with the Islamic tradition of the Shura, highlighting its central role in the Islamist discursive tradition.Peer Reviewe

Longitudinal Joint Modelling of Binary and Continuous Outcomes: A Comparison of Bridge and Normal Distributions

Background: Longitudinal joint models consider the variation caused by repeated measurements over time as well as the association among the response variables. In the case of combining binary and continuous response variables using generalized linear mixed models, integrating over a normally distributed random intercept in the binary logistic regression sub-model does not yield to a closed form. In this paper, we assessed the impact of assuming a Bridge distribution for the random intercept in the binary logistic regression submodel and compared the results to that of normal distribution.  Method: The response variables are combined through correlated random intercepts. The random intercept in the continuous outcome submodel follows a normal distribution. The random intercept in the binary outcome submodel follows a normal or Bridge distribution. The estimations were carried out using a likelihood-based approach in direct and conditional joint modeling approaches. To illustrate the performance of the models, a simulation study was conducted Results: Based on the simulation results and regardless of the joint modeling approach, the models with a Bridge distribution for the random intercept of the binary outcome resulted in a slightly more accurate estimations and better performance. Conclusion: In addition to the fact that assuming a bridge distribution for the random intercept in binary logistic regression yields to the same interpretation of parameter estimates in marginal and conditional forms, our study revealed that even if the random intercept of binary logistic regression is normally distributed, assuming a Bridge distribution in the model will result in more accurate results.&nbsp

Lignin-Stabilized Doxorubicin Microemulsions: Synthesis, Physical Characterization, and In Vitro Assessments

Encapsulation of the chemotherapy agents within colloidal systems usually improves drug efficiency and decreases its toxicity. In this study, lignin (LGN) (the second most abundant biopolymer next to cellulose on earth) was employed to prepare novel doxorubicin (DOX)-loaded oil-in-water (O/W) microemulsions with the aim of enhancing the bioavailability of DOX. The droplet size of DOX-loaded microemulsion was obtained as ≈ 7.5 nm by dynamic light scattering (DLS) analysis. The entrapment efficiency (EE) % of LGN/DOX microemulsions was calculated to be about 82%. In addition, a slow and sustainable release rate of DOX (68%) was observed after 24 h for these microemulsions. The cytotoxic effects of standard DOX and LGN/DOX microemulsions on non-malignant (HUVEC) and malignant (MCF7 and C152) cell lines were assessed by application of a tetrazolium (MTT) colorimetric assay. Disruption of cell membrane integrity was investigated by measuring intracellular lactate dehydrogenase (LDH) leakage. In vitro experiments showed that LGN/DOX microemulsions induced noticeable morphological alterations and a greater cell-killing effect than standard DOX. Moreover, LGN/DOX microemulsions significantly disrupted the membrane integrity of C152 cells. These results demonstrate that encapsulation and slow release of DOX improved the cytotoxic efficacy of this anthracycline agent against cancer cells but did not improve its safety towards normal human cells. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of microemulsions as a promising drug carrier for overcoming pharmacokinetic limitations

Application of Nanotechnology for Sensitive Detection of Low-Abundance Single-Nucleotide Variations in Genomic DNA: A Review

Single-nucleotide polymorphisms (SNPs) are the simplest and most common type of DNA variations in the human genome. This class of attractive genetic markers, along with point mutations, have been associated with the risk of developing a wide range of diseases, including cancer, cardiovascular diseases, autoimmune diseases, and neurodegenerative diseases. Several existing methods to detect SNPs and mutations in body fluids have faced limitations. Therefore, there is a need to focus on developing noninvasive future polymerase chain reaction (PCR)–free tools to detect low-abundant SNPs in such specimens. The detection of small concentrations of SNPs in the presence of a large background of wild-type genes is the biggest hurdle. Hence, the screening and detection of SNPs need efficient and straightforward strategies. Suitable amplification methods are being explored to avoid high-throughput settings and laborious efforts. Therefore, currently, DNA sensing methods are being explored for the ultrasensitive detection of SNPs based on the concept of nanotechnology. Owing to their small size and improved surface area, nanomaterials hold the extensive capacity to be used as biosensors in the genotyping and highly sensitive recognition of single-base mismatch in the presence of incomparable wild-type DNA fragments. Different nanomaterials have been combined with imaging and sensing techniques and amplification methods to facilitate the less time-consuming and easy detection of SNPs in different diseases. This review aims to highlight some of the most recent findings on the aspects of nanotechnology-based SNP sensing methods used for the specific and ultrasensitive detection of low-concentration SNPs and rare mutations

Quantum Dots: Synthesis, Antibody Conjugation, and HER2-Receptor Targeting for Breast Cancer Therapy

Breast cancer is becoming one of the main lethal carcinomas in the recent era, and its occurrence rate is increasing day by day. There are different breast cancer biomarkers, and their overexpression takes place in the metastasis of cancer cells. The most prevalent breast cancer biomarker is the human epidermal growth factor receptor2 (HER2). As this biomarker is overexpressed in malignant breast tissues, it has become the main focus in targeted therapies to fight breast cancer. There is a cascade of mechanisms involved in metastasis and cell proliferation in cancer cells. Nanotechnology has become extremely advanced in targeting and imaging cancerous cells. Quantum dots (QDs) are semiconductor NPs, and they are used for bioimaging, biolabeling, and biosensing. They are synthesized by different approaches such as top-down, bottom-up, and synthetic methods. Fully human monoclonal antibodies synthesized using transgenic mice having human immunoglobulin are used to target malignant cells. For the HER2 receptor, herceptin(®) (trastuzumab) is the most specific antibody (Ab), and it is conjugated with QDs by using different types of coupling mechanisms. This quantum dot monoclonal antibody (QD-mAb) conjugate is localized by injecting it into the blood vessel. After the injection, it goes through a series of steps to reach the intracellular space, and bioimaging of specifically the HER2 receptor occurs, where apoptosis of the cancer cells takes place either by the liberation of Ab or the free radicals

Breast Cancer Vaccines: New insights into Immunomodulatory and Nano-therapeutic Approaches

Breast cancer (BC) is known to be a highly heterogeneous disease that is clinically subdivided into four primary molecular subtypes, each having distinct morphology and clinical implications. These subtypes are principally defined by hormone receptors and other proteins involved (or not involved) in BC development. BC therapeutic vaccines [including peptide-based vaccines, protein-based vaccines, nucleic acid-based vaccines (DNA/RNA vaccines), bacterial/viral-based vaccines, and different immune cell-based vaccines] have emerged as an appealing class of cancer immunotherapeutics when used alone or combined with other immunotherapies. Employing the immune system to eliminate BC cells is a novel therapeutic modality. The benefit of active immunotherapies is that they develop protection against neoplastic tissue and readjust the immune system to an anti-tumor monitoring state. Such immunovaccines have not yet shown effectiveness for BC treatment in clinical trials. In recent years, nanomedicines have opened new windows to increase the effectiveness of vaccinations to treat BC. In this context, some nanoplatforms have been designed to efficiently deliver molecular, cellular, or subcellular vaccines to BC cells, increasing the efficacy and persistence of anti-tumor immunity while minimizing undesirable side effects. Immunostimulatory nano-adjuvants, liposomal-based vaccines, polymeric vaccines, virus-like particles, lipid/calcium/phosphate nanoparticles, chitosan-derived nanostructures, porous silicon microparticles, and selenium nanoparticles are among the newly designed nanostructures that have been used to facilitate antigen internalization and presentation by antigen-presenting cells, increase antigen stability, enhance vaccine antigenicity and remedial effectivity, promote antigen escape from the endosome, improve cytotoxic T lymphocyte responses, and produce humoral immune responses in BC cells. Here, we summarized the existing subtypes of BC and shed light on immunomodulatory and nano-therapeutic strategies for BC vaccination. Finally, we reviewed ongoing clinical trials on BC vaccination and highlighted near-term opportunities for moving forward

Active Targeted of Nanoparticles for Delivery of Poly(ADP ribose) Polymerase (PARP) Inhibitors: A Preliminary Review

Nanotechnology has revolutionized novel drug delivery strategies through establishing nanoscale drug carriers, such as niosomes, liposomes, nanomicelles, dendrimers, polymeric micelles, and nanoparticles (NPs). Owing to their desirable cancer-targeting efficacy and controlled release, these nanotherapeutic modalities are broadly used in clinics to improve the efficacy of small-molecule inhibitors. Poly(ADP-ribose) polymerase (PARP) family members engage in various intracellular processes, including DNA repair, gene transcription, signal transduction, cell cycle regulation, cell division, and antioxidant response. PARP inhibitors are synthetic small-molecules that have emerged as one of the most successful innovative strategies for targeted therapy in cancer cells harboring mutations in DNA repair genes. Despite these advances, drug resistance and unwanted side effects are two significant drawbacks to using PARP inhibitors in the clinic. Recently, the development of practical nanotechnology-based drug delivery systems has tremendously improved the efficacy of PARP inhibitors. NPs can specifically accumulate in the leaky vasculature of the tumor and cancer cells and release the chemotherapeutic moiety in the tumor microenvironment. On the contrary, NPs are usually unable to permeate across the body's normal organs and tissues; hence the toxicity is zero to none. NPs can modify the release of encapsulated drugs based on the composition of the coating substance. Delivering PARP inhibitors without modulation often leads to the toxic effect; therefore, a delivery vehicle is essential to encapsulate them. Various nanocarriers have been exploited to deliver PARP inhibitors in different cancers. Through this review, we hope to cast light on the most innovative advances in applying PARP inhibitors for therapeutic purposes.(Comunidad de Madrid

A Report on the Environmental Impact of the Texas LoanSTAR Program from May 1989 to September 1995

There are a number of factors that influence emission factors. The three major pollutants considered in this analysis are CO2, SO2, and NOX. Emission factors from three different sources were considered for this report. This analysis shows that as of September, 1995, there has been a reduction in emissions of 1.88 million pounds of NOX, 1.19 million pounds of SO2, and 532 million pounds of CO2 through the implementation of energy conservation measures in the Texas LoanSTAR program.The Texas LoanSTAR (Loans to Save Taxes and Resources) program was created by the state of Texas in 1989 to lend money for energy conserving improvements, or retrofits, in public buildings. As of September 1995 the LoanSTAR program is measuring savings for 22 loan sites covering 153 buildings where retrofits have been fully or partially completed. The completed retrofits show $21.1 million in measured savings, which is more than 119% of the energy savings predicted by the energy auditors. This corresponds to 23.9% of the pre-retrofit consumption cost at these sites. Through energy savings, the Texas LoanSTAR program has made a significant contribution towards reducing hazardous environmental emissions

Multi-Functionalized Nanomaterials and Nanoparticles for Diagnosis and Treatment of Retinoblastoma

Retinoblastoma is a rare type of cancer, and its treatment, as well as diagnosis, is challenging, owing to mutations in the tumor-suppressor genes and lack of targeted, efficient, cost-effective therapy, exhibiting a significant need for novel approaches to address these concerns. For this purpose, nanotechnology has revolutionized the field of medicine with versatile potential capabilities for both the diagnosis, as well as the treatment, of retinoblastoma via the targeted and controlled delivery of anticancer drugs via binding to the overexpressed retinoblastoma gene. Nanotechnology has also generated massive advancements in the treatment of retinoblastoma based on the use of surface-tailored multi-functionalized nanocarriers; overexpressed receptor-based nanocarriers ligands (folate, galactose, and hyaluronic acid); lipid-based nanocarriers; and metallic nanocarriers. These nanocarriers seem to benchmark in mitigating a plethora of malignant retinoblastoma via targeted delivery at a specified site, resulting in programmed apoptosis in cancer cells. The effectiveness of these nanoplatforms in diagnosing and treating intraocular cancers such as retinoblastoma has not been properly discussed, despite the increasing significance of nanomedicine in cancer management. This article reviewed the recent milestones and future development areas in the field of intraocular drug delivery and diagnostic platforms focused on nanotechnology