Sulindac sulfide as a non-immune suppressive γ-secretase modulator to target triple-negative breast cancer.

Introduction: Triple-negative breast cancer (TNBC) comprises a heterogeneous group of clinically aggressive tumors with high risk of recurrence and metastasis. Current pharmacological treatment options remain largely limited to chemotherapy. Despite promising results, the efficacy of immunotherapy and chemo-immunotherapy in TNBC remains limited.

Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses.

A critical feature of cancer is the ability to induce immunosuppression and evade immune responses. Tumor-induced immunosuppression diminishes the effectiveness of endogenous immune responses and decreases the efficacy of cancer immunotherapy. In this study, we describe a new immunosuppressive pathway in which adenosine promotes Casitas B-lineage lymphoma b (Cbl-b)-mediated Notch1 degradation, causing suppression of CD8+ T-cells effector functions.

Impact of temperature and biomass augmentation on biosulfur-driven autotrophic denitrification in membrane bioreactors treating real nitrate-contaminated groundwater.

Nitrate (NO) contamination of groundwater is a major health concern worldwide as it can lead to serious illnesses such as methemoglobinemia and cancer. Autotrophic denitrification is a smart approach for treating groundwater, being typically organic-deficient. Lately, biogenic sulfur (S) has emerged as a sustainable, free, and high-efficiency substrate to fuel membrane bioreactors (MBRs) treating contaminated groundwater.

Sequential sulfur-based denitrification/denitritation and nanofiltration processes for drinking water treatment.

Efficient and cost-effective solutions for nitrogen removal are necessary to ensure the availability of safe drinking water. This study proposes a combined treatment for nitrogen-contaminated groundwater by sequential autotrophic nitrogen removal in a sulfur-packed bed reactor (SPBR) and excess sulfate rejection via nanofiltration (NF). Autotrophic nitrogen removal in the SPBR was investigated under both denitrification and denitritation conditions under different NO and NO loading rates (LRs) and feeding strategies (NO only, NO only, or both NO and NO in the feed).

Correction: Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

[This corrects the article DOI: 10.1371/journal.pone.

Dual inhibition of MEK1/2 and MEK5 suppresses the EMT/migration axis in triple-negative breast cancer through FRA-1 regulation.

Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. Constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway has been linked to chemoresistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT) when cells adopt a motile and invasive phenotype through loss of epithelial markers (CDH1), and acquisition of mesenchymal markers (VIM, CDH2). Although MAPK/ERK1/2 kinase inhibitors (MEKi) are useful antitumor agents in a clinical setting, including the Food and Drug Administration (FDA)-approved MEK1,2 dual inhibitors cobimetinib and trametinib, there are limitations to their clinical utility, primarily adaptation of the BRAF pathway and ocular toxicities.

Diverse and converging roles of ERK1/2 and ERK5 pathways on mesenchymal to epithelial transition in breast cancer.

The epithelial to mesenchymal transition (EMT) is characterized by a loss of cell polarity, a decrease in the epithelial cell marker E-cadherin, and an increase in mesenchymal markers including the zinc-finger E-box binding homeobox (ZEB1). The EMT is also associated with an increase in cell migration and anchorage-independent growth. Induction of a reversal of the EMT, a mesenchymal to epithelial transition (MET), is an emerging strategy being explored to attenuate the metastatic potential of aggressive cancer types, such as triple-negative breast cancers (TNBCs) and tamoxifen-resistant (TAMR) ER-positive breast cancers, which have a mesenchymal phenotype.

Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling.

Extracellular signal-regulated kinase (ERK5) is an essential regulator of cancer progression, tumor relapse, and poor patient survival. Epithelial to mesenchymal transition (EMT) is a complex oncogenic process, which drives cell invasion, stemness, and metastases. Activators of ERK5, including mitogen-activated protein kinase 5 (MEK5), tumor necrosis factor α (TNF-α), and transforming growth factor-β (TGF-β), are known to induce EMT and metastases in breast, lung, colorectal, and other cancers.

Evaluation of deacetylase inhibition in metaplastic breast carcinoma using multiple derivations of preclinical models of a new patient-derived tumor.

Metaplastic breast carcinoma (MBC) is a clinically aggressive and rare subtype of breast cancer, with similar features to basal-like breast cancers. Due to rapid growth rates and characteristic heterogeneity, MBC is often unresponsive to standard chemotherapies; and novel targeted therapeutic discovery is urgently needed. Histone deacetylase inhibitors (DACi) suppress tumor growth and metastasis through regulation of the epithelial-to-mesenchymal transition axis in various cancers, including basal-like breast cancers.

Self-forming dynamic membrane bioreactor for textile industry wastewater treatment.

The robustness of anaerobic dynamic membrane bioreactor (AnDMBR) for synthetic textile wastewater treatment was investigated. Textile wastewater may contain high concentrations of NaCl and sulfate, hence their impact on the AnDMBR performance was investigated in detail. A dynamic membrane was formed on a 20-μm pore sized nylon support layer at a constant flux of around 8 LMH.

ERK5 Is Required for Tumor Growth and Maintenance Through Regulation of the Extracellular Matrix in Triple Negative Breast Cancer.

Conventional mitogen-activated protein kinase (MAPK) family members regulate diverse cellular processes involved in tumor initiation and progression, yet the role of ERK5 in cancer biology is not fully understood. Triple-negative breast cancer (TNBC) presents a clinical challenge due to the aggressive nature of the disease and a lack of targeted therapies. ERK5 signaling contributes to drug resistance and metastatic progression through distinct mechanisms, including activation of epithelial-to-mesenchymal transition (EMT).

A novel screening approach comparing kinase activity of small molecule inhibitors with similar molecular structures and distinct biologic effects in triple-negative breast cancer to identify targetable signaling pathways.

Breast cancer affects women globally; the majority of breast cancer-related mortalities are due to metastasis. Acquisition of a mesenchymal phenotype has been implicated in the progression of breast cancer cells to an invasive, metastatic state. Triple-negative breast cancer (TNBC) subtypes have high rates of metastases, recurrence, and have poorer prognoses compared to other breast cancer types, partially due to lack of commonly targeted receptors.

Process optimization and filtration performance of an anaerobic dynamic membrane bioreactor treating textile wastewaters.

The study aimed at investigating the performance of anaerobic dynamic MBR (AnDMBR) for the treatment of synthetic textile wastewater. A laboratory scale anaerobic bioreactor was operated to test nylon mesh support materials with different pore sizes (20 μm, 53 μm and 100 μm). The performances of the AnDMBR were evaluated with a stimulated wastewater containing 1,000 mg.

General Surgery Operating Room Practice in Patients with COVID-19.

The virus COVID-19, which emerged in China in December 2019, was announced by the World Health Organization as a pandemic in January 2020. It is known that infection is not severe and may even progress without symptoms in patients who have come into contact with COVID-19. Although various organizations have been informed about how to take measures to protect the patient and the surgeon in case of diseases requiring urgent or elective surgery in people infected with COVID-19 or in cases with high suspicion, there is still no definite judgment between patients, physicians and health authorities.

Comparison of biogenic and chemical sulfur as electron donors for autotrophic denitrification in sulfur-fed membrane bioreactor (SMBR).

Two sulfur-oxidizing membrane bioreactors (SMBRs) performing autotrophic denitrification at different HRTs (6-26 h), one supplemented with biogenic elemental sulfur (S) and the other with chemically-synthesized elemental sulfur (S), were compared in terms of nitrate reduction rates, impact on membrane filtration and microbial community composition. Complete denitrification with higher rates (up to 286 mg N-NO/L d) was observed in the SMBR supplemented with S (SMBR), while nitrate was never completely reduced in the SMBR fed with S (SMBR). Trans membrane pressure was higher for SMBR due to smaller particle size and colloidal properties of S.

Notch Signaling Regulates Mitochondrial Metabolism and NF-κB Activity in Triple-Negative Breast Cancer Cells via IKKα-Dependent Non-canonical Pathways.

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival.

Notch Signaling in Myeloid Cells as a Regulator of Tumor Immune Responses.

Cancer immunotherapy, which stimulates or augments host immune responses to treat malignancies, is the latest development in the rapidly advancing field of cancer immunology. The basic principles of immunotherapies are either to enhance the functions of specific components of the immune system or to neutralize immune-suppressive signals produced by cancer cells or tumor microenvironment cells. When successful, these approaches translate into long-term survival for patients.

An Overview of Electron Acceptors in Microbial Fuel Cells.

Microbial fuel cells (MFC) have recently received increasing attention due to their promising potential in sustainable wastewater treatment and contaminant removal. In general, contaminants can be removed either as an electron donor via microbial catalyzed oxidization at the anode or removed at the cathode as electron acceptors through reduction. Some contaminants can also function as electron mediators at the anode or cathode.

A novel elemental sulfur-based mixotrophic denitrifying membrane bioreactor for simultaneous Cr(VI) and nitrate reduction.

This study aims at investigating the simultaneous nitrate and chromate reduction by combining the advantages of sulfur-based autotrophic denitrification, heterotrophic denitrification and membrane bioreactor (MBR) technologies. A laboratory-scale MBR equipped with hydrophilic flat sheet polyethersulfone (PES) membranes (0.45μm) was used to evaluate the performance of mixotrophic denitrification at varying nitrate and Cr(VI) concentrations.

Heterotrophic-autotrophic sequential system for reductive nitrate and perchlorate removal.

Nitrate and perchlorate were identified as significant water contaminants all over the world. This study aims at evaluating the performances of the heterotrophic-autotrophic sequential denitrification process for reductive nitrate and perchlorate removal from drinking water. The reduced nitrate concentration in the heterotrophic reactor increased with increasing methanol concentrations and the remaining nitrate/nitrite was further removed in the following autotrophic denitrifying process.

Performances of anaerobic and aerobic membrane bioreactors for the treatment of synthetic textile wastewater.

This study aims at comparatively evaluating anaerobic and aerobic MBRs for the treatment of azo-dye containing synthetic wastewater. Also, the filtration performances of AnMBR and AeMBR were compared under similar operating conditions. In both MBRs, high COD removal efficiencies were observed.

Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin.

Introduction: Hypertriglyceridaemia (HT)-induced pancreatitis rarely occurs unless triglyceride levels exceed 1000 mg/dl. Hypertriglyceridaemia over 1,000 mg/dl can provoke acute pancreatitis (AP) and its persistence can worsen the clinical outcome. In contrast, a rapid decrease in triglyceride level is beneficial.

A FAK scaffold inhibitor disrupts FAK and VEGFR-3 signaling and blocks melanoma growth by targeting both tumor and endothelial cells.

Melanoma has the highest mortality rate of all skin cancers and a major cause of treatment failure is drug resistance. Tumors heterogeneity requires novel therapeutic strategies and new drugs targeting multiple pathways. One of the new approaches is targeting the scaffolding function of tumor related proteins such as focal adhesion kinase (FAK).

Inhibiting the interaction of cMET and IGF-1R with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo.

Pancreatic cancer is one of the most lethal diseases with no effective treatment. Previously, we have shown that FAK is overexpressed in pancreatic cancer and plays a key role in cancer cell survival and proliferation. FAK has been shown to interact with growth factor receptors including cMET and IGF-1R.

Disruption of the protein interaction between FAK and IGF-1R inhibits melanoma tumor growth.

FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other and thereby activate crucial signaling pathways that benefit cancer cells. Inhibition of FAK and IGF-1R function has been shown to significantly decrease cancer cell proliferation and increase sensitivity to chemotherapy and radiation treatment. As a novel approach in human melanoma, we evaluated the effect of a small-molecule compound that disrupts the protein interaction of FAK and IGF-1R.