Synthesis of Tryptamine-Thiazolidin-4-one Derivatives and the Combined and Evaluation of their Biological Activity and Cytotoxicity.

Tryptamine, a monoamine alkaloid with an indole ring structure, is derived from the decarboxylation of the amino acid tryptophan, which is present in fungi, plants, and animals. Tryptamine analogues hold significant therapeutic potential due to their broad pharmacological activities, including roles as neurotransmitters and potential therapeutic agents for various diseases. Structural modifications of tryptamine enhance receptor selectivity and metabolic stability, improving therapeutic efficacy.

Claudin and transmembrane receptor protein gene expressions are reversely correlated in peritumoral brain edema.

Introduction: Peritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema.

Objective: This study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions.

Super-enhancer hijacking drives ectopic expression of hedgehog pathway ligands in meningiomas.

Hedgehog signaling mediates embryologic development of the central nervous system and other tissues and is frequently hijacked by neoplasia to facilitate uncontrolled cellular proliferation. Meningiomas, the most common primary brain tumor, exhibit Hedgehog signaling activation in 6.5% of cases, triggered by recurrent mutations in pathway mediators such as SMO.

Silencing of the MEG3 gene promoted anti-cancer activity and drug sensitivity in glioma.

Aberrant expression of MEG3 has been shown in various cancers. The purpose of this study is to evaluate the effect of MEG3 on glioma cells and the use of potential chemotherapeutics in glioma by modulating MEG3 expression. Cell viability, migration and chemosensitivity were assayed.

Comparison of anti-spike IgG, anti-spike IgA levels and neutralizing antibody activity induced by CoronaVac and BNT162b2 vaccines in patients with inflammatory rheumatic diseases receiving immunosuppressive therapy.

Background: The importance of COVID-19 vaccination for patients on immunosuppressive (IS) medication has increased due to the high risk of severe disease or mortality. Different vaccines have varying efficacy rates against symptomatic COVID-19, ranging from 46.8% to 95%.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

Background: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging.

Objective: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.

Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Sonder in the Dardanelles.

Sonder is a green alga belonging to the Caulerpaceae family. This is the first chemical investigation of in the Dardanelles which resulted in the isolation of four compounds, caulerpin (1), monomethyl caulerpinate (2), beta-sitosterol (3), and palmitic acid (4). Their structures were elucidated by spectroscopic analyses including 1D- and 2D NMR and mass.

Glycopolymer and Poly(β-amino ester)-Based Amphiphilic Block Copolymer as a Drug Carrier.

Glycopolymers are synthetic macromolecules having pendant sugar moieties and widely utilized to target cancer cells. They are usually considered as a hydrophilic segment of amphiphilic block copolymers to fabricate micelles as drug carriers. A novel amphiphilic block copolymer, namely, poly(2-deoxy-2-methacrylamido-d-glucose--2-hydroxyethyl methacrylate)--poly(β-amino ester) [P(MAG--HEMA)--PBAE], with active cancer cell targeting potential and pH responsivity was prepared.

A novel BH3 mimetic Bcl-2 inhibitor promotes autophagic cell death and reduces in vivo Glioblastoma tumor growth.

Anti-apoptotic members of the Bcl-2 family proteins play central roles in the regulation of cell death in glioblastoma (GBM), the most malignant type of brain tumor. Despite the advances in GBM treatment, there is still an urgent need for new therapeutic approaches. Here, we report a novel 4-thiazolidinone derivative BH3 mimetic, BAU-243 that binds to Bcl-2 with a high affinity.

IDH1 mutation activates mTOR signaling pathway, promotes cell proliferation and invasion in glioma cells.

Background: Glioma is the most common type of brain tumors and isocitrate dehydrogenase (IDH1) gene is the most prominent molecular marker about the disease prognosis, response to therapy and patient survival. There are conflicting data about the effect of IDH1 mutation on glial cell proliferation, invasion and migration characteristics. The effect of IDH1 mutation on mTOR signaling pathway, which has key roles in tumorigenesis process, is limited and previous data is controversial.

Antiangiogenic Molecules Suppressed Meningioma-Induced Neovascularization: A Corneal Angiogenesis Study.

Aim: To investigate the angiogenic effects of bevacizumab and imatinib on different meningioma tissue grades.

Material And Methods: In this study, in silico analysis of angiogenesis-related gene expression was carried out using previously reported datasets. Messenger ribonucleic acid expressions of VEGFA, VEGFB, PDGFRA, and PDGFRB genes were obtained from two different meningioma transcriptome datasets.

Review on Methods, High-throughput Screening Techniques, and Cell Culture Based Assays for SARS-CoV-2.

The COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to have high incidence and mortality rate globally. To meet the increasingly growing demand for new therapeutic drugs and vaccines, researchers are developing different diagnostic techniques focused on screening new drugs in clinical use, developing an antibody targeting a SARS-CoV-2 receptor, or interrupting infection/replication mechanisms of SARS-CoV-2. Although many prestigious research publications are addressing this subject, there is no open access platform where all experimental techniques for COVID-19 research can be seen as a whole.

Investigation of neuro-inflammatory parameters in a cuprizone induced mouse model of multiple sclerosis.

Cuprizone, copper chelator, treatment of mouse is a toxic model of multiple sclerosis (MS) in which oligodendrocyte death, demyelination and remyelination can be observed. Understanding T and B cell subset as well as their cytokines involved in MS pathogenesis still requires further scrutiny to better understand immune component of MS. The study presented here, aimed to evaluate relevant cytokines, lymphocytes, and gene expressions profiles during demyelination and remyelination in the cuprizone mouse model of MS.

The neutralization effect of montelukast on SARS-CoV-2 is shown by multiscale in silico simulations and combined in vitro studies.

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV-2. We initially demonstrated the dual inhibition profile of montelukast through multiscale molecular modeling studies.

Instant determination of the artemisinin from various Artemisia annua L. extracts by LC-ESI-MS/MS and their in-silico modelling and in vitro antiviral activity studies against SARS-CoV-2.

Introduction: Numerous efforts in natural product drug development are reported for the treatment of Coronavirus. Based on the literature, among these natural plants Artemisia annua L. shows some promise for the treatment of SARS-CoV-2.

Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS-CoV-2: A Combined in silico and in vitro Study.

In the current study, we used 7922 FDA approved small molecule drugs as well as compounds in clinical investigation from NIH's NPC database in our drug repurposing study. SARS-CoV-2 main protease as well as Spike protein/ACE2 targets were used in virtual screening and top-100 compounds from each docking simulations were considered initially in short molecular dynamics (MD) simulations and their average binding energies were calculated by MM/GBSA method. Promising hit compounds selected based on average MM/GBSA scores were then used in long MD simulations.

Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing.

The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int).

Association of MTHFR, MTRR and RAD54L Gene Variations with Meningioma and Correlation with Tumor's Histopathological Characteristics on Turkish Cohort.

Aim: To elucidate the association of the MTHFR, MTRR, and RAD54L gene variations with meningioma in Turkish cohort.

Material And Methods: DNAs were isolated from 87 retrospective meningioma samples. The MTHFR, MTRR, and RAD54L gene hotspot regions were amplified with specific primers via polymerase chain reaction (PCR), and next-generation sequencing (NGS) was performed.

Hybrid and TR-FRET-Guided Discovery of Novel BCL-2 Inhibitors.

B-Cell lymphoma 2 (BCL-2) regulates cell death in humans. In this study, combined multiscale approaches and studies were employed. A small-molecule library that includes more than 210 000 compounds was used.

Genome-wide identification of Chiari malformation type I associated candidate genes and chromosomal variations.

Chiari malformation type I (CMI) is a brain malformation that is characterized by herniation of the cerebellum into the spinal canal. Chiari malformation type I is highly heterogeneous; therefore, an accurate explanation of the pathogenesis of the disease is often not possible. Although some studies showed the role of genetics in CMI, the involvement of genetic variations in CMI pathogenesis has not been thoroughly elucidated.

Associations of meningioma molecular subgroup and tumor recurrence.

Background: We and others have identified mutually exclusive molecular subgroups of meningiomas; however, the implications of this classification for clinical prognostication remain unclear. Integrated genomic and epigenomic analyses implicate unique oncogenic processes associated with each subgroup, suggesting the potential for divergent clinical courses. The aim of this study was to understand the associated clinical outcomes of each subgroup, as this could optimize treatment for patients.

An Integrated in silico Approach and in vitro Study for the Discovery of Small-Molecule USP7 Inhibitors as Potential Cancer Therapies.

The ubiquitin-specific protease 7 (USP7) is a highly promising well-validated target for a variety of malignancies. USP7 is critical in regulating the tumor suppressor p53 along with numerous epigenetic modifiers and transcription factors. Previous studies showed that USP7 inhibitors led to increased levels of p53 and anti-proliferative effects in hematological and solid tumor cell lines.

Proposing novel MDM2 inhibitors: Combined physics-driven high-throughput virtual screening and in vitro studies.

The mouse double minute 2 (MDM2) protein acts as a negative regulator of the p53 tumor suppressor. It directly binds to the N terminus of p53 and promotes p53 ubiquitination and degradation. Since the most common p53-suppressing mechanisms involve the MDM2, proposing novel inhibitors has been the focus of many in silico and also experimental studies.

Integrating Ligand and Target-Driven Based Virtual Screening Approaches With Human Cell Line Models and Time-Resolved Fluorescence Resonance Energy Transfer Assay to Identify Novel Hit Compounds Against BCL-2.

Antiapoptotic members of -/-2 (BCL-2) family proteins are one of the overexpressed proteins in cancer cells that are oncogenic targets. As such, targeting of BCL-2 family proteins raises hopes for new therapeutic discoveries. Thus, we used multistep screening and filtering approaches that combine structure and ligand-based drug design to identify new, effective BCL-2 inhibitors from a small molecule database (Specs SC), which includes more than 210,000 compounds.

Development of a Rapid and Sensitive IDH1/2 Mutation Detection Method for Glial Tumors and a Comparative Mutation Analysis of 236 Glial Tumor Samples.

Background: The presence of mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) in glioma tumors is correlated with good prognosis upon standard-of-care treatment. Therefore, information on whether the glioma tumor has IDH1/2 mutations could be used in the correct diagnosis and management of glial tumors. The two most common techniques used to detect IDH1/2 mutations, immunohistochemistry (IHC) and Sanger sequencing, are prone to missing these mutations, especially if the tumor cells that carry the mutations constitute a small minority of the tumor itself.