Transcriptome analysis displays new molecular insights into the mechanisms of action of Mebendazole in gastric cancer cells.

Gastric cancer (GC) is a common cancer worldwide. Therefore, searching for effective treatments is essential, and drug repositioning can be a promising strategy to find new potential drugs for GC therapy. For the first time, we sought to identify molecular alterations and validate new mechanisms related to Mebendazole (MBZ) treatment in GC cells through transcriptome analysis using microarray technology.

Molecular characterization and biomarker discovery in gastric cancer progression through transcriptome meta-analysis.

Gastric cancer (GC) is a leading cause of cancer-related deaths globally. It is a multifactorial, molecularly heterogeneous disease whose carcinogenic patterns are not yet well established, requiring the development of new tools for better understanding and identifying gastric carcinogenesis. From this point of view, this study aims to compare transcriptome profiles from The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD) and a human-merged dataset to identify potential biomarkers and therapeutic targets.

Association of PARP1 Expression Levels and Clinical Parameters in Different Leukemic Subtypes With Translocation.

Background/aim: Although the reciprocal translocation t(9;22)(q34;q11) is a hallmark of chronic myeloid leukemia (CML), it is also present in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Depending on the gene's breakpoint, it is possible to obtain three isoforms, among which p190 stands out for the poor prognosis it induces whenever it appears. Due to the genomic instability induced by BCR::ABL1, it is proposed to expand the applicability of poly-ADP-ribose polymerase-1 (PARP1) and its inhibitors in hematological neoplasms.

Long-COVID olfactory dysfunction: allele E4 of apolipoprotein E as a possible protective factor.

Background:  Olfactory dysfunction (OD) represents a frequent manifestation of the coronavirus disease 2019 (COVID-19). Apolipoprotein E (APOE) is a protein that interacts with the angiotensin-converting enzyme receptor, essential for viral entry into the cell. Previous publications have suggested a possible role of APOE in COVID-19 severity.

Molecular and Clinical Insights in the Increasing Detection of in Adult Acute Myeloid Leukemia Patients.

Background/aim: Acute myeloid leukemia (AML) is a myeloproliferative neoplasm marked by abnormal clonal expansion of hematopoietic progenitor cells, displaying karyotypic aberrations and genetic mutations as prognostic indicators. The World Health Organization (WHO) and the European LeukemiaNet guidelines categorize BCR::ABL1 p190+ AML as high risk. This study explored the identification of the increased incidence of BCR::ABL1 p190+ in our AML population.

Three dimensional reconstruction of skin with melanoma: A model for study of invasion in vitro.

Melanoma is a type of tumor skin with high metastatic potential. Reconstructed human skin, development for pre-clinic assay, are make using primary human cells, but with same limitations. The aim this study was to characterize a cell culture model, with structure similar to human skin containing melanoma cells entirely from cell lines.

Association of CD38+ Immunophenotyping Biomarker With a Better Prognosis in Elderly Acute Myeloid Leukemia Patients.

Background/aim: The relevance of cytogenetic markers as prognostic risk factors has been demonstrated in a vast number of studies, with many prognostication tools utilizing these factors to determine treatment approaches. Patients aged above 60 years represent an important subgroup of acute myeloid leukemia (AML) patients, especially because they usually exhibit a poorer cytogenetic landscape and are less suitable for intensive treatments. The importance of evaluating prognostic parameters in AML, especially in low-income countries, prompted an investigation into CD38 expression and its effects.

A Review on Anaplastic Lymphoma Kinase (ALK) Rearrangements and Mutations: Implications for Gastric Carcinogenesis and Target Therapy.

Gastric adenocarcinoma is a complex disease with diverse genetic modifications, including Anaplastic Lymphoma Kinase (ALK) gene changes. The ALK gene is located on chromosome 2p23 and encodes a receptor tyrosine kinase that plays a crucial role in embryonic development and cellular differentiation. ALK alterations can result from gene fusion, mutation, amplification, or overexpression in gastric adenocarcinoma.

Validation of Endogenous Control Genes by Real-Time Quantitative Reverse Transcriptase Polymerase Chain Reaction for Acute Leukemia Gene Expression Studies.

Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase (), Abelson murine leukemia viral oncogene human homolog 1 (), Hypoxanthine phosphoribosyl-transferase 1 (), Ribosomal protein lateral stalk subunit P0 (), β-actin () and TATA box binding protein (). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.

Development and Clinical Applications of PI3K/AKT/mTOR Pathway Inhibitors as a Therapeutic Option for Leukemias.

Leukemias are hematological neoplasms characterized by dysregulations in several cellular signaling pathways, prominently including the PI3K/AKT/mTOR pathway. Since this pathway is associated with several important cellular mechanisms, such as proliferation, metabolism, survival, and cell death, its hyperactivation significantly contributes to the development of leukemias. In addition, it is a crucial prognostic factor, often correlated with therapeutic resistance.

Recalculating the Route: Repositioning Antimicrobial Peptides for Cancer Treatment.

Resistance to antimicrobial drugs has been considered a public health problem. Likewise, the increasing resistance of cancer cells to drugs currently used in therapy has also become a problem. Therefore, the research and development of synthetic peptides bring a new perspective on the emergence of new drugs for treating this resistance since bioinformatics provides a means to optimize these molecules and save time and costs in research.

PARP1 Characterization as a Potential Biomarker for p190+ Acute Lymphoblastic Leukemia.

Detection of t(9;22), and consequent fusion, is still a marker of worse prognosis for acute lymphoblastic leukemia (ALL), with resistance to tyrosine-kinase inhibitor therapy being a major obstacle in the clinical practice for this subset of patients. In this study, we investigated the effectiveness of targeting poly-ADP-ribose polymerase (PARP) in a model of p190+ ALL, the most common isoform to afflict ALL patients, and demonstrated the use of experimental PARP inhibitor (PARPi), AZD2461, as a therapeutic option with cytotoxic capabilities similar to that of imatinib, the current gold standard in medical care. We characterized cytostatic profiles, induced cell death, and biomarker expression modulation utilizing cell models, also providing a comprehensive genome-wide analysis through an aCGH of the model used, and further validated PARP1 differential expression in samples of ALL p190+ patients from local healthcare institutions, as well as in larger cohorts of online and readily available datasets.

Three snake venoms from Bothrops genus induced apoptosis and cell cycle arrest in K562 human leukemic cell line.

Cancer is indisputably one of the leading causes of death worldwide. Snake venoms are a potential source of bioactive compounds, complex mixtures constituted mainly of proteins and peptides with several pharmacological possibilities, including the potential to inhibit tumoral cell growth. In the present study, it was evaluated the antitumor effect of crude venom of Bothrops erythromelas (BeV), Bothrops jararaca (from Southern and Southeastern- BjsV and BjsdV, respectively) and Bothrops alternatus (BaV) in in vitro Chronic myeloid leukemia (CML) cancer cell line model.

Effects of whey protein supplementation on gut microbiota of Wistar rats with valproic acid-induced autism symptoms.

To evaluate the effects of whey protein (WP) supplementation (1.24 mg/g, 24 days) in rats with autism spectrum disorder (ASD) induced by valproic acid (400 mg/kg, single dose). Wistar rats (14 days old) were divided into four groups: control, ASD, ASD plus WP and WP.

Vasorelaxant effect of Alpinia zerumbet's essential oil on rat resistance artery involves blocking of calcium mobilization.

Alpinia zerumbet is a plant from the Zingiberaceae family, popularly used for hypertension treatment. Several studies have demonstrated Alpinia zerumbet vasodilator effect on conductance vessels but not on resistance vessels. Thereby, the aim of this study was to verify the vasodilator effect of the essential oil of Alpinia zerumbet (EOAz) on isolated rat resistance arteries and characterize its mechanism of action.

Mebendazole targets essential proteins in glucose metabolism leading gastric cancer cells to death.

Gastric cancer (GC) is among the most-diagnosed and deadly malignancies worldwide. Deregulation in cellular bioenergetics is a hallmark of cancer. Based on the importance of metabolic reprogramming for the development and cancer progression, inhibitors of cell metabolism have been studied as potential candidates for chemotherapy in oncology.

Effect of CYB2B6 (c.516G>T), CYP2C9 (c.1075A>C) and UGT1A9 (c.98T>C) polymorphisms on propofol pharmacokinetics in patients submitted to colonoscopy: a cohort study.

Background: The aim of this study was to investigate the effect of CYB2B6 (c.516G>T, rs3745274), CYP2C9 (c.1075A>C, rs1057910) and UGT1A9 (c.

Association between Immunophenotypic Parameters and Molecular Alterations in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy that occurs due to alterations such as genetic mutations, chromosomal translocations, or changes in molecular levels. These alterations can accumulate in stem cells and hematopoietic progenitors, leading to the development of AML, which has a prevalence of 80% of acute leukemias in the adult population. Recurrent cytogenetic abnormalities, in addition to mediating leukemogenesis onset, participate in its evolution and can be used as established diagnostic and prognostic markers.

Behavioral and neuroinflammatory changes caused by glyphosate: Base herbicide in mice offspring.

Background: Glyphosate is a pesticide considered of low toxicity, but scientific evidences show it can be harmful to health. This study aimed to evaluate the toxicity in mice offspring exposed to glyphosate-based herbicide (GBH) during the intrauterine period.

Methods: Female matrices received glyphosate 0.

The Role of WRAP53 in Cell Homeostasis and Carcinogenesis Onset.

The WD repeat containing antisense to TP53 () gene codifies an antisense transcript for tumor protein p53 (), stabilization (WRAP53α), and a functional protein (WRAP53β, WDR79, or TCAB1). The WRAP53β protein functions as a scaffolding protein that is important for telomerase localization, telomere assembly, Cajal body integrity, and DNA double-strand break repair. WRAP53β is one of many proteins known for containing WD40 domains, which are responsible for mediating a variety of cell interactions.

Kinase Inhibitor Screening Displayed as a Possible Therapeutic Biomarker for Gastric Cancer.

Despite advances in cancer chemotherapy, gastric cancer (GC) continues to have high recurrence rates and poor prognosis with limited treatment options. Understanding the etiology of GC and developing more effective, less harmful therapeutic approaches are vital and urgent. Therefore, this work describes a novel kinase target in malignant gastric cells as a potential therapeutic strategy.

Kinase Inhibition in Multiple Myeloma: Current Scenario and Clinical Perspectives.

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease.

Anticancer potential of mebendazole against chronic myeloid leukemia: and studies revealed new insights about the mechanism of action.

Chronic myeloid leukemia (CML) is caused by constitutively active fusion protein BCR-ABL1, and targeting ABL1 is a promising therapy option. Imatinib, dasatinib, and nilotinib have all been shown to work effectively in clinical trials. ABL1 mutations, particularly the T315I gate-keeper mutation, cause resistance in patients.