A Novel Allosteric Inhibitor Targets PLK1 in Triple Negative Breast Cancer Cells.

While Polo-like kinase 1 (PLK1) inhibitors have shown promise in clinical settings for treating triple-negative breast cancer tumors and other solid tumors, they are limited by their ability to bind non-selectively to the ATP kinase domain. Therefore, we sought to develop a PLK1 allosteric inhibitor targeting the PLK1 T-loop (a switch responsible for activation) and evaluate its effects in triple-negative breast cancer cells. A novel compound, RK-10, was developed based on an in silico model, and its effects on specificity, viability, migration, and cell cycle regulation in MCF-10A and MDA-MB 231 cells were evaluated.

Pt- and Pd-modified transition metal nitride catalysts for the hydrogen evolution reaction.

Hydrogen production electrochemical splitting of water using renewable electricity represents a promising strategy. Currently, platinum group metals (PGMs) are the best performing hydrogen evolution reaction (HER) catalysts. Thus, the design of non-PGM catalysts or low-loading PGM catalysts is essential for the commercial development of hydrogen generation technologies electrochemical splitting of water.

Design and discovery of a high affinity, selective and β-arrestin biased 5-HT Receptor Agonist.

Compound , 5-chloro-2-(2-(3,4-dihydroisoquinolin-2(1H)-yl)ethyl)-2,3-dihydro-1H-inden-1-one was previously reported from our laboratory showing high affinity binding to the 5-HT receptor ( = 0.5 nM). However, compound racemizes readily upon enantiomeric separation.

Epigallocatechin-3-Gallate (EGCG): New Therapeutic Perspectives for Neuroprotection, Aging, and Neuroinflammation for the Modern Age.

Alzheimer's and Parkinson's diseases are the two most common forms of neurodegenerative diseases. The exact etiology of these disorders is not well known; however, environmental, molecular, and genetic influences play a major role in the pathogenesis of these diseases. Using Alzheimer's disease (AD) as the archetype, the pathological findings include the aggregation of Amyloid Beta (Aβ) peptides, mitochondrial dysfunction, synaptic degradation caused by inflammation, elevated reactive oxygen species (ROS), and cerebrovascular dysregulation.

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents.

The purpose of this study was to evaluate if phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), and their combination, could protect mice from Paclitaxel-induced peripheral neuropathy (PIPN). Six groups of C57BL/6J mice (n = 6) were used in this study. The mice were given paclitaxel (PTX) (8 mg/kg/day, i.

Glyceollins Trigger Anti-Proliferative Effects in Hormone-Dependent Aromatase-Inhibitor-Resistant Breast Cancer Cells through the Induction of Apoptosis.

Aromatase inhibitors (AIs) are standard treatment for estrogen-dependent postmenopausal breast tumors; however, resistance develops leading to tumor relapse and metastasis. We previously demonstrated that glyceollin inhibits proliferation, survival, and migration of hormone-independent letrozole-resistant breast cancer. Since many AI-resistant tumors remain hormone-dependent, identifying distinctions between estrogen-receptor-positive (ER+) and ER-negative (ER-) AI-resistant tumor response to therapy is critical.

Achieving complete electrooxidation of ethanol by single atomic Rh decoration of Pt nanocubes.

SignificanceDirect ethanol fuel cells are attracting growing attention as portable power sources due to their advantages such as higher mass-energy density than hydrogen and less toxicity than methanol. However, it is challenging to achieve the complete electrooxidation to generate 12 electrons per ethanol, resulting in a low fuel utilization efficiency. This manuscript reports the complete ethanol electrooxidation by engineering efficient catalysts via single-atom modification.

Anticancer and chemosensitization effects of cannabidiol in 2D and 3D cultures of TNBC: involvement of GADD45α, integrin-α5, -β5, -β1, and autophagy.

To date, promising therapy for triple negative breast cancer (TNBC) remains a serious concern clinically because of poor prognosis, resistance, and recurrence. Herein, anti-cancer potential of synthetic cannabidiol (CBD; Purisys, GA; GMP grade) was explored either alone or as a chemosensitizer followed by post-treatment with doxorubicin (DOX) in TNBC (i.e.

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges.

In this focused progress review, the most widely accepted methods of transdermal drug delivery are hypodermic needles, transdermal patches and topical creams. However, microneedles (MNs) (or microneedle arrays) are low-invasive 3D biomedical constructs that bypass the skin barrier and produce systemic and localized pharmacological effects. In the past, biomaterials such as carbohydrates, due to their physicochemical properties, have been extensively used to manufacture microneedles (MNs).

Assessing the effectiveness of a community health advisor plus screen to save educational intervention on stool-based testing adherence in an African American safety net clinic population: study protocol for a randomized pragmatic trial.

Background: Colorectal cancer (CRC) is the second most deadly cancer affecting US adults and is also one of the most treatable cancers when detected at an earlier clinical stage of disease through screening. CRC health disparities experienced by African Americans are due in part to the later stage of diagnosis, suggesting the importance of improving African Americans' CRC screening participation. The national Screen to Save (S2S) initiative employs a community health educator to deliver CRC screening education which can be tailored for specific populations, and such approaches have increased CRC screening rates in disadvantaged and racial/ethnic minority populations.

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy.

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products.

Flax and Sorghum: Multi-Element Contents and Nutritional Values within 210 Varieties and Potential Selection for Future Climates to Sustain Food Security.

The Dietary Guidelines for Americans recommends giving priority to nutrient-dense foods while decreasing energy-dense foods. Although both flax () and sorghum () are rich in various essential minerals, their ionomes have yet to be investigated. Furthermore, previous studies have shown that elevated CO levels could reduce key nutrients in crops.

A Facile Synthesis of Noble-Metal-Free Catalyst Based on Nitrogen Doped Graphene Oxide for Oxygen Reduction Reaction.

A simple method for the mechanochemical synthesis of an effective metal-free electrocatalyst for the oxygen reduction reaction was demonstrated. A nitrogen-doped carbon material was obtained by grinding a mixture of graphene oxide and melamine in a planetary ball mill. The resulting material was characterized by XPS, EPR, and Raman and IR spectroscopy.

Image-based documentation of vulvodynia pain location.

Better documentation of vulvar pain is needed. We examined pain locations marked on general body and genital specific outlines among women with vulvodynia. 62 women (mean age 32.

Unraveling the Mechanisms of Zinc Efficiency in Crop Plants: From Lab to Field Applications.

Global food security and sustainability in the time of pandemics (COVID-19) and a growing world population are important challenges that will require optimized crop productivity under the anticipated effects of climate change [...

Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR), contributing to aggressive metastatic disease. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me), a glycyrrhetinic acid derivative, reportedly improves the therapeutic response to erlotinib (ERL), an EGFR tyrosine kinase inhibitor. In the present study, we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R (ERL-resistant) cells to ERL.

Therapeutic Potential of Thymoquinone in Triple-Negative Breast Cancer Prevention and Progression through the Modulation of the Tumor Microenvironment.

To date, the tumor microenvironment (TME) has gained considerable attention in various areas of cancer research due to its role in driving a loss of immune surveillance and enabling rapid advanced tumor development and progression. The TME plays an integral role in driving advanced aggressive breast cancers, including triple-negative breast cancer (TNBC), a pivotal mediator for tumor cells to communicate with the surrounding cells via lymphatic and circulatory systems. Furthermore, the TME plays a significant role in all steps and stages of carcinogenesis by promoting and stimulating uncontrolled cell proliferation and protecting tumor cells from the immune system.

Triple Isozyme Lactic Acid Dehydrogenase Inhibition in Fully Viable MDA-MB-231 Cells Induces Cytostatic Effects That Are Not Reversed by Exogenous Lactic Acid.

A number of aggressive human malignant tumors are characterized by an intensified glycolytic rate, over-expression of lactic acid dehydrogenase A (LDHA), and subsequent lactate accumulation, all of which contribute toward an acidic peri-cellular immunosuppressive tumor microenvironment (TME). While recent focus has been directed at how to inhibit LDHA, it is now becoming clear that multiple isozymes of LDH must be simultaneously inhibited in order to fully suppress lactic acid and halt glycolysis. In this work we explore the biochemical and genomic consequences of an applied triple LDH isozyme inhibitor (A, B, and C) (GNE-140) in MDA-MB-231 triple-negative breast cancer cells (TNBC) cells.

Synthetic Optimization and MAPK Pathway Activation Anticancer Mechanism of Polyisoprenylated Cysteinyl Amide Inhibitors.

Abnormalities of the MAPK pathway play vital roles in cancer initiation and progression. RAS GTPases that are key upstream mediators of the pathway are mutated in 30% of human cancers. Polyisoprenylated cysteinyl amide inhibitors (PCAIs) were designed as potential targeted therapies against the RAS-driven cancers.

Application of Machine Learning Algorithms in Breast Cancer Diagnosis and Classification.

Breast cancer continues to be the most frequent cancer in females, affecting about one in 8 women and causing the highest number of cancer-related deaths in females worldwide despite remarkable progress in early diagnosis, screening, and patient management. All breast lesions are not malignant, and all the benign lesions do not progress to cancer. However, the accuracy of diagnosis can be increased by a combination or preoperative tests such as physical examination, mammography, fine-needle aspiration cytology, and core needle biopsy.

Diversity in blueberry genotypes and developmental stages enables discrepancy in the bioactive compounds, metabolites, and cytotoxicity.

Eight blueberry cultivars at three developmental stages were investigated for metabolite profiling, antioxidant, and anticancer activities. Cultivars- and developmental stages-variations were determined in total phenolic, flavonoid, DPPH, and FRAP antioxidant assays. The anticancer capacity was equal against A549, HepG2, and Caco-2 cancer cells, whereas the inhibition rate was dose-, incubation period-, cultivar-, and developmental stages-dependent.

Polycentropus aileenae n. sp. (Trichoptera: Polycentropodidae), a caddisfly species from the eastern Nearctic, with new state records for members of the Polycentropus confusus Species Group.

A new eastern Nearctic species of tube-making caddisfly of the genus Polycentropus Curtis 1835 (Trichoptera: Polycentropodidae) is described and illustrated based on adult males and females. Polycentropus aileenae n. sp.

Physician Training Related to Environmental Hazards near Ash Superfund Sites.

Physicians do not receive formal environmental health training in medical schools. The objectives of this study were to provide health care providers with basic environmental medicine training to better advise, treat or refer patients in the community and to observe any differences in the environmental medicine learning gains pre/post- test assessment. To rectify the problem of the lack of physicians' training related to environmental hazards, we conducted an environmental health workshop which targeted physicians living near Health Zone 1, Superfund ash sites.

Practical School Nutrition Program May Reduce Food Neophobia.

The study's purpose was to evaluate an intervention to reduce fruit and vegetable food neophobia and influence attitudes and behaviors among children using a four-month, non-experimental, before-and-after intervention. Participants were children aged 5-11 years in an intervention school (IS) and a control school (CS). Children were offered fruit or vegetable samples weekly utilizing school-specific psychosocial and educational practices to encourage participation.

Density functional theory studies of transition metal carbides and nitrides as electrocatalysts.

Transition metal carbides and nitrides are interesting non-precious materials that have been shown to replace or reduce the loading of precious metals for catalyzing several important electrochemical reactions. The purpose of this review is to summarize density functional theory (DFT) studies, describe reaction pathways, identify activity and selectivity descriptors, and present a future outlook in designing carbide and nitride catalysts for the hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), nitrogen reduction reaction (NRR), CO reduction reaction (CORR) and alcohol oxidation reactions. This topic is of high interest to scientific communities working in the field of electrocatalysis and this review should provide theoretical guidance for the rational design of improved carbide and nitride electrocatalysts.