Expression of Ceramide Synthases in Mice and Their Roles in Regulating Acyl-Chain Sphingolipids: A Framework for Baseline Levels and Future Implications in Aging and Disease.

Sphingolipids are an important class of lipids present in all eukaryotic cells that regulate critical cellular processes. Disturbances in sphingolipid homeostasis have been linked to several diseases in humans. Ceramides are central in sphingolipid metabolism and are largely synthesized by six ceramide synthase (CerS) isoforms (CerS1-6), each with a preference for different fatty acyl chain lengths.

Is there a need for change in cancer survivorship care? A qualitative exploration of survivor experiences and needs at the Sydney Cancer Survivorship Centre Clinic.

Purpose: Effective cancer survivorship care is contingent on a comprehensive understanding and management of the dynamic needs of cancer survivors. The Sydney Cancer Survivorship Centre (SCSC) clinic established a holistic, multidisciplinary model of survivorship care. We aimed to explore survivors' experiences and perceptions of the clinic, and to identify their unmet needs.

Targeting sphingosine kinase 1 in p53KO thymic lymphoma.

Sphingosine kinase 1 (SK1) is a key sphingolipid enzyme that is upregulated in several types of cancer, including lymphoma which is a heterogenous group of malignancies. Treatment for lymphoma has improved significantly by the introduction of new therapies; however, subtypes with tumor protein P53 (p53) mutations or deletion have poor prognosis, making it critical to explore new therapeutic strategies in this context. SK1 has been proposed as a therapeutic target in different types of cancer; however, the effect of targeting SK1 in cancers with p53 deletion has not been evaluated yet.

A novel HSPB1 mouse model of Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth Disease (CMT) is a commonly inherited peripheral polyneuropathy. Clinical manifestations for this disease include symmetrical distal polyneuropathy, altered deep tendon reflexes, distal sensory loss, foot deformities, and gait abnormalities. Genetic mutations in heat shock proteins have been linked to CMT2.

Ceramide as an endothelial cell surface receptor and a lung-specific lipid vascular target for circulating ligands.

The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins.

ACSL1 is a key regulator of inflammatory and macrophage foaming induced by short-term palmitate exposure or acute high-fat feeding.

Foamy and inflammatory macrophages play pathogenic roles in metabolic disorders. However, the mechanisms that promote foamy and inflammatory macrophage phenotypes under acute-high-fat feeding (AHFF) remain elusive. Herein, we investigated the role of acyl-CoA synthetase-1 (ACSL1) in favoring the foamy/inflammatory phenotype of monocytes/macrophages upon short-term exposure to palmitate or AHFF.

Upregulation of sphingosine kinase 1 in response to doxorubicin generates an angiogenic response via stabilization of Snail.

Sphingosine kinase 1 (SK1) converts the pro-death lipid sphingosine to the pro-survival sphingosine-1-phosphate (S1P) and is upregulated in several cancers. DNA damaging agents, such as the chemotherapeutic doxorubicin (Dox), have been shown to degrade SK1 protein in cancer cells, a process dependent on wild-type p53. As mutations in p53 are very common across several types of cancer, we evaluated the effects of Dox on SK1 in p53 mutant cancer cells.

Alkaline ceramidase catalyzes the hydrolysis of ceramides via a catalytic mechanism shared by Zn2+-dependent amidases.

Human alkaline ceramidase 3 (ACER3) is one of three alkaline ceramidases (ACERs) that catalyze the conversion of ceramide to sphingosine. ACERs are members of the CREST superfamily of integral-membrane hydrolases. All CREST members conserve a set of three Histidine, one Aspartate, and one Serine residue.

Community pharmacists' experiences of working during lockdown.

Background: Transmission of the novel coronavirus strain, SARS-CoV-2, caused many health services to reach crisis points worldwide. As infection rates rose, many countries implemented 'lockdown' periods where only essential services could remain open; this included community pharmacies in the UK. This study retrospectively explores the experiences of community pharmacists during the first lockdown period of the pandemic in the UK, helping us to learn for the future if another pandemic were to arise.

Neutral ceramidase deficiency protects against cisplatin-induced acute kidney injury.

Cisplatin is a commonly used chemotherapeutic for the treatment of many solid organ cancers; however, its effectiveness is limited by the development of acute kidney injury (AKI) in 30% of patients. AKI is driven by proximal tubule cell death, leading to rapid decline in renal function. It has previously been shown that sphingolipid metabolism plays a role in regulating many of the biological processes involved in cisplatin-induced AKI.

1-Deoxysphinganine initiates adaptive responses to serine and glycine starvation in cancer cells via proteolysis of sphingosine kinase.

Cancer cells may depend on exogenous serine, depletion of which results in slower growth and activation of adaptive metabolic changes. We previously demonstrated that serine and glycine (SG) deprivation causes loss of sphingosine kinase 1 (SK1) in cancer cells, thereby increasing the levels of its lipid substrate, sphingosine (Sph), which mediates several adaptive biological responses. However, the signaling molecules regulating SK1 and Sph levels in response to SG deprivation have yet to be defined.

GRASP55 regulates intra-Golgi localization of glycosylation enzymes to control glycosphingolipid biosynthesis.

The Golgi apparatus, the main glycosylation station of the cell, consists of a stack of discontinuous cisternae. Glycosylation enzymes are usually concentrated in one or two specific cisternae along the cis-trans axis of the organelle. How such compartmentalized localization of enzymes is achieved and how it contributes to glycosylation are not clear.

A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.

A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer.

Adsorption of Organic Dyes on Magnetic Iron Oxide Nanoparticles. Part I: Mechanisms and Adsorption-Induced Nanoparticle Agglomeration.

This series of two papers is devoted to the effect of organic dye (methylene blue, MB; or methyl orange, MO) adsorption on the surface of either bare or citrate-coated magnetic iron oxide nanoparticles (IONPs) on their primary agglomeration (in the absence of an applied magnetic field) and secondary field-induced agglomeration. The present paper (Part I) is focused on physicochemical mechanisms of dye adsorption and adsorption-induced primary agglomeration of IONPs. Dye adsorption to oppositely charged IONPs is found to be mostly promoted by electrostatic interactions and is very sensitive to pH and ionic strength variations.

Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.

Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer.

Ceramide kinase regulates TNF-α-induced immune responses in human monocytic cells.

Ceramide kinase (CERK) phosphorylates ceramide to produce ceramide-1-phosphate (C1P), which is involved in the development of metabolic inflammation. TNF-α modulates inflammatory responses in monocytes associated with various inflammatory disorders; however, the underlying mechanisms remain not fully understood. Here, we investigated the role of CERK in TNF-α-induced inflammatory responses in monocytes.

Public perception on opioids & pain management after major surgery.

Background: In the US, opioids are overprescribed after surgery contributing to the opioid epidemic. Patients' expectations regarding postoperative opioids remains unclear.

Methods: A representative survey using random-digit dial telephone sampling of English-speaking adults in US was conducted from August 28 to December 11, 2019.

Sphingosine kinase 1 downregulation is required for adaptation to serine deprivation.

It has been well-established that cancer cells often display altered metabolic profiles, and recent work has concentrated on how cancer cells adapt to serine removal. Serine can be either taken exogenously or synthesized from glucose, and its regulation forms an important mechanism for nutrient integration. One of the several important metabolic roles for serine is in the generation of bioactive sphingolipids since it is the main substrate for serine palmitoyltransferase, the initial and rate-limiting enzyme in the synthesis of sphingolipids.

How to Support a Surgeon Scientist: Lessons from National Institutes of Health K-Award Recipients.

Background: Success in academic surgery is challenging and research cannot survive without funding. NIH K-awards are designed to mentor junior investigators to achieve independence. As a result we aimed to study K awardees in departments of surgery and learn from their experience.

Transcriptional Regulation of Sphingosine Kinase 1.

Once thought to be primarily structural in nature, sphingolipids have become increasingly appreciated as second messengers in a wide array of signaling pathways. Sphingosine kinase 1, or SK1, is one of two sphingosine kinases that phosphorylate sphingosine into sphingosine-1-phosphate (S1P). S1P is generally pro-inflammatory, pro-angiogenic, immunomodulatory, and pro-survival; therefore, high SK1 expression and activity have been associated with certain inflammatory diseases and cancer.