Identification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy.

Objective And Significance: Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary.

A Phase 1b study of the OxPhos inhibitor ME-344 with bevacizumab in refractory metastatic colorectal cancer.

Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC).

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.

The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

Pearls and Pitfalls of T1-Weighted Neuroimaging: A Primer for the Clinical Radiologist.

All T1-weighted images are built upon one of two fundamental pulse sequences, spin-echo and gradient echo, each of which has distinct signal characteristics and clinical applications. Moreover, within each broadly defined category of T1-weighting, acquisition parameters can be modified to affect image quality, contrast, and scan duration; each tailored sequence has unique advantages, drawbacks, clinical indications, and potential artifacts. In this review, we describe key features that distinguish different types of T1-weighted sequences and discuss the utility of each sequence for specific clinical settings, including neuro-oncology, vasculopathy, and pediatric neuroradiology.

AMPK Activation Serves as a Common Pro-Survival Pathway in Esophageal Adenocarcinoma Cells.

Esophageal adenocarcinoma (EAC) is a subtype of esophageal cancer that is difficult to treat, with overall poor survival and frequent recurrence despite curative-intent treatment strategies. There is limited understanding of EAC resistance mechanisms to chemotherapy or radiation. We have found that the AMP-activated protein kinase (AMPK) can serve a pro-survival function in EAC cells in response to cytotoxic treatments.

Intracranial meningioma: A review of recent and emerging data on the utility of preoperative imaging for management.

Meningiomas are the most common neoplasms of the central nervous system, accounting for approximately 40% of all brain tumors. Surgical resection represents the mainstay of management for symptomatic lesions. Preoperative planning is largely informed by neuroimaging, which allows for evaluation of anatomy, degree of parenchymal invasion, and extent of peritumoral edema.

Brain Cell-based Genetic Subtyping and Drug Repositioning for Alzheimer Disease.

Alzheimer's Disease (AD) is characterized by its complex and heterogeneous etiology and gradual progression, leading to high drug failure rates in late-stage clinical trials. In order to better stratify individuals at risk for AD and discern potential therapeutic targets we employed a novel procedure utilizing cell-based co-regulated gene networks and polygenic risk scores (cbPRSs). After defining genetic subtypes using extremes of cbPRS distributions, we evaluated correlations of the genetic subtypes with previously defined AD subtypes defined on the basis of domain-specific cognitive functioning and neuroimaging biomarkers.

Comparative transcriptomic and phenotypic analysis of induced pluripotent stem cell hepatocyte-like cells and primary human hepatocytes.

Primary human hepatocytes (PHHs) are used extensively for in vitro liver cultures to study hepatic functions. However, limited availability and invasive retrieval prevent their widespread use. Induced pluripotent stem cells exhibit significant potential since they can be obtained non-invasively and differentiated into hepatic lineages, such as hepatocyte-like cells (iHLCs).

Advances in Neuro-Oncological Imaging: An Update on Diagnostic Approach to Brain Tumors.

This study delineates the pivotal role of imaging within the field of neurology, emphasizing its significance in the diagnosis, prognostication, and evaluation of treatment responses for central nervous system (CNS) tumors. A comprehensive understanding of both the capabilities and limitations inherent in emerging imaging technologies is imperative for delivering a heightened level of personalized care to individuals with neuro-oncological conditions. Ongoing research in neuro-oncological imaging endeavors to rectify some limitations of radiological modalities, aiming to augment accuracy and efficacy in the management of brain tumors.

Microstructured Gel Polymer Electrolyte and an Interdigital Electrode-Based Iontronic Barometric Pressure Sensor with High Resolution over a Broad Range.

We present a novel iontronic barometric pressure sensor based on a gel polymer electrolyte and interdigital electrodes with a much simpler structure than that of existing devices. By introducing high-density microstructures on the gel polymer electrolyte and one side electrode arrangement configuration, the developed sensor offers high performances with an ultrahigh resolution of 10 Pa, an ultrawide barometric pressure-response range from -92 to 7 kPa, a fast response time of ∼15 ms, and excellent long-term stability. The single pressure sensor is able to detect positive and negative barometric pressures without needing any additional means and can operate as a barometric altimeter with a resolution of about one-floor height.

A novel pipeline for prioritizing cancer type-specific therapeutic vulnerabilities using DepMap identifies PAK2 as a target in head and neck squamous cell carcinomas.

There is limited guidance on exploiting the genome-wide loss-of-function CRISPR screens in cancer Dependency Map (DepMap) to identify new targets for individual cancer types. This study integrated multiple tools to filter these data in order to seek new therapeutic targets specific to head and neck squamous cell carcinoma (HNSCC). The resulting pipeline prioritized 143 targetable dependencies that represented both well-studied targets and emerging target classes like mitochondrial carriers and RNA-binding proteins.

DDD-028: A potent, neuroprotective, non-opioid compound for the treatment of diabetic neuropathy.

Diabetic neuropathy (DN) is a painful, chronic ailment that affects a large segment of diabetic population worldwide. Current medications such as pregabalin or duloxetine treat only the pain symptom associated with DN, but not the underlying nerve damage. DDD-028 (1) is a small molecule that displays potent pain-relieving activity in streptozotocin (STZ)-induced rodent model of DN.

A Review of Artificial Neural Network Models Applied to Predict Indoor Air Quality in Schools.

Background: Indoor air quality (IAQ) in schools can affect the performance and health of occupants, especially young children. Increased public attention on IAQ during the COVID-19 pandemic and bushfires have boosted the development and application of data-driven models, such as artificial neural networks (ANNs) that can be used to predict levels of pollutants and indoor exposures.

Methods: This review summarises the types and sources of indoor air pollutants (IAP) and the indicators of IAQ.

Broad-spectrum neuroprotection exerted by DDD-028 in a mouse model of chemotherapy-induced neuropathy.

Neurotoxicity of chemotherapeutics involves peculiar alterations in the structure and function, including abnormal nerve signal transmission, of both the peripheral and central nervous system. The lack of effective pharmacological approaches to prevent chemotherapy-induced neurotoxicity necessitates the identification of innovative therapies. Recent evidence suggests that repeated treatment with the pentacyclic pyridoindole derivative DDD-028 can exert both pain-relieving and glial modulatory effects in mice with paclitaxel-induced neuropathy.

Comparison of Lumbosacral Fusion Grade in Patients after Transforaminal and Anterior Lumbar Interbody Fusion with Minimum 2-Year Follow-Up.

Objective: Generally, anterior lumbar interbody fusion (ALIF) was believed superior to transforaminal lumbar interbody fusion (TLIF) in induction of fusion. However, many studies have reported comparable results in lumbosacral fusion rate between the two approaches. This study aimed to evaluate the realistic lumbosacral arthrodesis rates following ALIF and TLIF in patients with degenerative spondylolisthesis as measured by CT and radiology.

Computational high-throughput screening and approaches identify CB-006-3; A novel PI3K-BRAF dual targeted inhibitor against melanoma.

Malignant melanoma is characterized by both genetic and molecular alterations that activate phosphoinositide 3-kinase (PI3K), and RAS/BRAF pathways. In this work, through diversity-based high-throughput virtual screening we identified a lead molecule that selectively targets PI3K and BRAF kinases. Computational screening, Molecular dynamics simulation and MMPBSA calculations were performed.

Computational docking and analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt.

Targeted therapies are gaining global attention to tackle Renal Cancer (RC). This study aims to screen FPMXY-14 (novel arylidene analogue) for Akt inhibition by computational and methods. FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis.

Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.

Estrogen receptor (ER) α is expressed in a subset of patient-derived acute myeloid leukemia (AML) cells, whereas Akt is predominantly expressed in most types of AML. Targeting AML with dual inhibitors is a novel approach to combat the disease. Herein, we examined a novel small molecule, 3-(4-isopropyl) benzylidene-8-ethoxy,6-methyl, chroman-4-one (SBL-060), capable of targeting AML cells by inhibiting ERα and Akt kinase.

Bovine Airway Models: Approaches for Investigating Bovine Respiratory Disease.

Bovine respiratory disease (BRD) is a multifactorial condition where different genera of bacteria, such as , , , and , and viruses, like bovine respiratory syncytial virus, bovine viral diarrhea virus, and bovine herpes virus-1, infect the lower respiratory tract of cattle. These pathogens can co-infect cells in the respiratory system, thereby making specific treatment very difficult. Currently, the most common models for studying BRD include a submerged tissue culture (STC), where monolayers of epithelial cells are typically covered either in cellular or spent biofilm culture medium.

Investigating Trans-differentiation of Glioblastoma Cells in an 3D Model of the Perivascular Niche.

Glioblastoma multiforme (GBM) is the deadliest form of brain cancer, responsible for over 50% of adult brain tumors. A specific region within the GBM environment is known as the perivascular niche (PVN). This area is defined as within approximately 100 μm of vasculature and plays an important role in the interactions between endothelial cells (ECs), astrocytes, GBM cells, and stem cells.

BV6 enhances apoptosis in Lung cancer cells by ameliorating caspase expressions through attenuation of XIAP, cIAP-1, and cIAP-2 proteins.

Objective: The present study aimed to investigate the inhibitory role of second mitochondria determined activator of caspases mimetic on inhibitor of apoptosis proteins (IAPs) and regulation of caspases in nonsmall cell lung cancer cell line.

Materials And Methods: Dimethyl sulfoxide and 3-(4, 5-dimethyl thizol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was done to determine the IC of BV6 using NCI-H23 cell line. The levels of mRNA of X-linked IAP (XIAP), cellular IAP (cIAP-1), cIAP-2, caspase-6, and caspase-7 in H23 cell line were evaluated by a quantitative real-time polymerase chain reaction, while their protein expressions were tested using western blotting.

Insilco and Invitro approaches identify novel dual PI3K/AKT pathway inhibitors to control acute myeloid leukemia cell proliferations.

Acute myeloid leukemia (AML) is characterized by disruption of intracellular signaling due to aberration of extracellular signaling pathways, namely PI3K/AKT cascade, by dysregulating erythropoiesis and myelopoiesis. Therefore, inhibition of PI3K/AKT, either individually, or by dual inhibitors, is shown to be effective in suppression of tumorigenesis. To increase the therapeutic viability and decrease adverse effects, including cytotoxicity due to off-target kinase inhibitions, customized targeted pharmacological agents are needed that would have greater treatment potential.