Article
Biochemistry & Molecular Biology
Nuria Puig, Jose Rives, Montserrat Estruch, Ana Aguilera-Simon, Noemi Rotllan, Mercedes Camacho, Nuria Colome, Francesc Canals, Jose Luis Sanchez-Quesada, Sonia Benitez
Summary: Electronegative low-density lipoprotein (LDL(-)) is a modified fraction of human plasma LDL with atherogenic properties, including increased bioactive lipid mediator content. The present study suggests the presence of ceramidase (CDase)-like activity in LDL(-), which is associated with the increased sphingosine (Sph) content. However, the exact origin of this activity remains unknown and requires further investigation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yasharah Raza, Jane Atallah, Chiara Luberto
Summary: Dysregulation of sphingolipid metabolism plays a complex role in hematological malignancies, contributing to the design of combinatorial therapeutic regimens and reducing resistance to standard therapies. Inhibitors targeting specific nodes of the sphingolipid pathway significantly decrease leukemic cell survival. The recent advances in this field focus on the latter part of the last decade.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Albena Momchilova, Roumen Pankov, Alexander Alexandrov, Tania Markovska, Stefan Pankov, Plamen Krastev, Galya Staneva, Evgenia Vassileva, Nikolai Krastev, Adriana Pinkas
Summary: This study analyzed the lipid composition and sphingolipid-catabolizing enzymes in the blood of multiple sclerosis (MS) patients and found changes in the levels of sphingomyelin and its products. The activity of acid sphingomyelinase and alkaline ceramidase also showed alterations. Additionally, differences in the ratios of saturated, unsaturated, and polyunsaturated fatty acids were observed, which could potentially serve as markers for distinguishing MS patients from healthy controls. The application of lipid analysis in medical practice could contribute to more precise diagnosis, analysis of disease progression, and evaluation of therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Daniela I. Staquicini, Marina Cardo-Vila, Jimmy A. Rotolo, Fernanda I. Staquicini, Fenny H. F. Tang, Tracey L. Smith, Aditya Ganju, Carmine Schiavone, Prashant Dogra, Zhihui Wang, Vittorio Cristini, Ricardo J. Giordano, Michael G. Ozawa, Wouter H. P. Driessen, Bettina Proneth, Glauco R. Souza, Lina M. Brinker, Achraf Noureddine, Ashley J. Snider, Daniel Canals, Juri G. Gelovani, Irina Petrache, Rubin M. Tuder, Lina M. Obeid, Yusuf A. Hannun, Richard N. Kolesnick, C. Jeffrey Brinker, Renata Pasqualini, Wadih Arap
Summary: The vascular endothelium in individual organs has specialized functions and unique molecular targets. This study identifies a lipid-based receptor system in the lung vascular endothelium, where CGSPGWVRC peptide interacts with C16-ceramide to trigger ceramide-rich platform formation and activate ceramide production. This peptide shows lung selectivity dependent on ceramide production and has potential applications in pulmonary imaging and lung immunization against COVID-19.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Medicinal
Kan Yang, Keyi Nong, Fei Xu, Yu Chen, Jinying Yu, Lizhi Lin, Xiao Hu, Youzhi Wang, Ting Li, Jibin Dong, Jinxin Wang
Summary: In this study, a series of benzene-heterocyclic-based ASM inhibitors were designed, synthesized, and screened, and some compounds showed favorable inhibitory activity against recombinant human ASM. Compound 4i exhibited good pharmacokinetic properties and in vivo inhibitory activity against ASM, reducing the level of ceramide in mice plasma and liver. Moreover, 4i was found to decrease lipid plaques, plasma ceramide concentration, and Ox-LDL levels, and to regulate cell inflammation induced by LPS and Ox-LDL by modulating the levels of ceramide and sphingomyelin. Overall, this study demonstrates the potential of ASM as an effective target for treating atherosclerosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Daniel Canals, Silvia Salamone, Bruno Jaime Santacreu, Daniel Aguilar, Maria Jose Hernandez-Corbacho, Anne G. Ostermeyer-Fay, Meaghan Greene, Erika Nemeth, John D. Haley, Lina M. Obeid, Yusuf A. Hannun
Summary: The study revealed that low doses of the chemotherapeutic compound doxorubicin result in dysregulation of cytoskeletal proteins, enhancing cancer cell migration, which could explain the reported effects of doxorubicin worsening cancer metastasis in animal models.
Article
Biochemistry & Molecular Biology
Mazen Aseeri, Jose Luis Abad, Antonio Delgado, Gemma Fabrias, Gemma Triola, Josefina Casas
Summary: Ceramide plays a crucial role in regulating cellular senescence and apoptosis. Acid ceramidase (AC) reduces Ceramide levels, which is abnormally expressed in various cancers. However, the lack of suitable screening formats has hindered AC inhibitor discovery. In this study, a fluorogenic assay was adapted to a 384-well plate format, overcoming this limitation. The optimized platform successfully screened a library of 4100 compounds and identified several hits with potency ranges of 2-25 μM, belonging to different chemical classes. These inhibitors showed selectivity for neutral ceramidase and retained activity in cells, serving as a basis for further chemical optimization.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
A. Ra Kho, Bo Young Choi, Song Hee Lee, Dae Ki Hong, Beom Seok Kang, Si Hyun Lee, Sang Won Suh
Summary: The administration of imipramine after hypoglycemia significantly reduces neuronal death and improves cognitive function, suggesting it as a promising therapeutic tool for preventing hypoglycemia-induced neuronal death.
Article
Cell Biology
Yuan Jiang, Xingxuan He, Calogera M. Simonaro, Bin Yi, Edward H. Schuchman
Summary: The study demonstrates that recombinant acid ceramidase has therapeutic potential in hepatic ischemia reperfusion injury in mice, reducing damage and decreasing oxidative stress and inflammation. Changes in sphingolipid metabolism play a crucial role in the injury, and administration of acid ceramidase can alter sphingolipid levels and other pathologic changes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Plant Sciences
Hong-Yun Zeng, He-Nan Bao, Yi-Li Chen, Ding-Kang Chen, Kun Zhang, Shuai-Kang Liu, La Yang, Yong-Kang Li, Nan Yao
Summary: This study reveals that two classes of ceramide synthases differentially regulate EDS1/PAD4-dependent programmed cell death and immunity in Arabidopsis by subtly controlling long-chain bases and ceramides.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Cell Biology
Nina Geiger, Louise Kersting, Jan Schlegel, Linda Stelz, Sofie Faehr, Viktoria Diesendorf, Valeria Roll, Marie Sostmann, Eva-Maria Koenig, Sebastian Reinhard, Daniela Brenner, Sibylle Schneider-Schaulies, Markus Sauer, Jurgen Seibel, Jochen Bodem
Summary: The study demonstrates that fluoxetine and its derivative AKS466 can interfere with the replication of SARS-CoV-2 by inhibiting acid ceramidase activity. The findings suggest that acid ceramidase may serve as a host factor for SARS-CoV-2.
Article
Cell Biology
Ahmed Elsherbini, Zhihui Zhu, Zainuddin Quadri, Simone M. Crivelli, Xiaojia Ren, Hemendra J. Vekaria, Priyanka Tripathi, Liping Zhang, Wenbo Zhi, Erhard Bieberich
Summary: We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate their role in Alzheimer's disease (AD). Our findings suggest that sEVs from female mice contain more astrocyte-derived sEVs and have a higher likelihood of binding to Aβ, a hallmark protein in AD. We also discovered that sEVs from female brains have higher levels of acid sphingomyelinase (ASM) and ceramide, both important for sEV formation and Aβ binding. Moreover, sEVs from female 5xFAD mice were more neurotoxic, indicating their potential as distinct biomarkers for AD.
Review
Oncology
Marina Bataller, Almudena Sanchez-Garcia, Yoelsis Garcia-Mayea, Cristina Mir, Isabel Rodriguez, Matilde Esther LLeonart
Summary: Sphingolipids play a significant role in drug resistance, with complex metabolism and involvement of multiple enzymes, being associated with drug resistance in various types of cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Martha Franco, Agustina Cano-Martinez, Maria del Pilar Ramos-Godinez, Rebeca Lopez-Marure, Luis Donis-Maturano, Jose Santamaria Sosa, Rocio Bautista-Perez
Summary: This study investigated the potential of enzymes involved in sphingolipid catabolism as biomarkers for predicting early renal damage in diabetic and hypertensive rats. The activity of acid sphingomyelinase (aSMase) and neutral sphingomyelinase (nSMase) increased in the urine of diabetic rats and decreased in hypertensive rats, while only neutral ceramidase (nCDase) activity increased in the urine of diabetic rats. Immunofluorescence staining showed positive expression of nSMase, nCDase, and sphingosine kinase (SphK1) in various cells of the kidney. These findings suggest that aSMase and nCDase activity in urine could serve as novel predictors of early ultrastructural changes in the nephron, with aSMase and nCDase being potential markers for glomerular injury and nSMase for tubular injury in diabetic and hypertensive rats.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Miira M. M. Klemetti, Sruthi Alahari, Martin Post, Isabella Caniggia
Summary: Disturbances in lipid metabolism are common in diabetes. This study compared the placental sphingolipid metabolism in type 1 and type 2 diabetic pregnancies and non-diabetic controls. The results showed that placental ceramide levels were lower in diabetic pregnancies, but higher in cases of preeclampsia and poor glycemic control. Sphingosine kinases (SPHK) and sphingoid-1-phosphates (S1P) were elevated in diabetic pregnancies, especially in cases of fetal macrosomia.
Review
Obstetrics & Gynecology
Irving L. M. H. Aye, Catherine E. Aiken, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: This article discusses the metabolic basis for placental dysfunction and proposes that alterations in energy metabolism may explain various placental phenotypes in preeclampsia. It also suggests that placental metabolic reprogramming may be associated with severe preeclampsia phenotypes.
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
(2022)
Review
Obstetrics & Gynecology
Laura A. Wijs, Melinda R. Fusco, Dorota A. Doherty, Jeffrey A. Keelan, Roger J. Hart
Summary: The study revealed a trend towards a significantly increased risk of asthma in offspring conceived after ART, but not allergies.
HUMAN REPRODUCTION UPDATE
(2022)
Article
Pediatrics
Jacob Twiss, Alistair Stewart, Catherine A. Gilchrist, Jeffrey A. Keelan, Russell Metcalfe, Catherine A. Byrnes
Summary: This study investigates the efficacy of nebulised gentamicin in improving respiratory function in children with bronchiectasis. The results show that gentamicin reduces sputum bacterial density and inflammation, but does not lead to major improvements in clinical outcomes. Adherence to treatment was also a challenge.
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Article
Obstetrics & Gynecology
L. A. Wijs, D. A. Doherty, J. A. Keelan, V Panicker, P. Burton, J. L. Yovich, R. J. Hart
Summary: This study found no clinically relevant differences in thyroid function between adolescents and young adults conceived with and without ART.
HUMAN REPRODUCTION
(2022)
Article
Obstetrics & Gynecology
L. A. Wijs, D. A. Doherty, J. A. Keelan, P. Burton, J. L. Yovich, L. Beilin, T. A. Mori, R. C. Huang, L. A. Adams, J. K. Olynyk, O. T. Ayonrinde, B. Penova-Veselinovic, R. J. Hart
Summary: A study comparing cardiometabolic health parameters between adolescents conceived through ART and those conceived without ART found that the majority of health indicators were similar or more favorable in the ART group.
HUMAN REPRODUCTION
(2022)
Article
Obstetrics & Gynecology
Laura A. Wijs, Dorota A. Doherty, Jeffrey A. Keelan, Blagica Penova-Veselinovic, Peter Burton, John L. Yovich, Graham L. Hall, Peter D. Sly, Patrick G. Holt, Roger J. Hart
Summary: Adolescents conceived with assisted reproductive technologies (ART) show no difference in asthma prevalence compared to those conceived without, but have slightly altered lung function, increased rates of allergic rhinoconjunctivitis, food allergies, and positive skin prick testing.
REPRODUCTIVE BIOMEDICINE ONLINE
(2022)
Article
Cell Biology
Jane L. L. Tarry-Adkins, India G. G. Robinson, Rebecca M. M. Reynolds, Irving L. M. H. Aye, D. Stephen Charnock-Jones, Benjamin Jenkins, Albert Koulmann, Susan E. E. Ozanne, Catherine E. E. Aiken
Summary: Metformin concentrations in maternal, fetal, and placental tissues are closely related. Exposure to clinically relevant metformin concentrations in primary trophoblast cultures leads to reduced mitochondrial respiration, ATP production, and oxidative stress markers.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biology
Irving L. M. H. Aye, Sungsam Gong, Giulia Avellino, Roberta Barbagallo, Francesca Gaccioli, Benjamin J. Jenkins, Albert Koulman, Andrew J. Murray, D. Stephen Charnock-Jones, Gordon C. S. Smith
Summary: The function and dysfunction of the placenta differ between sexes, but the mechanisms responsible for this are unknown. This study reveals that differences in polyamine metabolism are associated with the escape from X chromosome inactivation of the gene encoding spermine synthase (SMS), which helps explain some of the sex differences observed in human placenta.
COMMUNICATIONS BIOLOGY
(2022)
Article
Respiratory System
Rachel E. Foong, Peter Franklin, Francesca Sanna, Graham L. Hall, Peter D. Sly, Eric B. Thorstensen, Dorota A. Doherty, Jeffrey A. Keelan, Roger J. Hart
Summary: This study investigated the effects of prenatal exposure to phthalates and bisphenol A (BPA) on asthma, allergy, and lung function outcomes from childhood to adulthood. The results showed that prenatal BPA exposure was associated with an increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with an increased likelihood of adult asthma in males. However, lung function was not adversely affected by prenatal exposure to these chemicals.
Article
Environmental Sciences
Ye'elah E. Berman, Dorota A. Doherty, Trevor A. Mori, Lawrence J. Beilin, Oyekoya T. Ayonrinde, Leon A. Adams, Rae-Chi Huang, John K. Olynyk, Jeffrey A. Keelan, John P. Newnham, Roger J. Hart
Summary: This study found that prenatal exposure to phthalate metabolites is associated with adverse metabolic profiles. Prenatal exposure to mono-carboxy-iso-octyl phthalate (MCiOP) is positively correlated with systolic blood pressure, while prenatal exposure to mono-n-butyl phthalate (MnBP) is associated with a higher incidence of non-alcoholic fatty liver disease (NAFLD). Prenatal exposure to Mono-3-carboxypropyl phthalate (MCPP) is linked to lower serum HDL-C levels, and higher prenatal exposure to mono-iso-butyl phthalate (MiBP) is associated with higher LDL-C levels. Additionally, mid-level prenatal exposure to mono-2-ethylhexyl phthalate (MEHP) metabolites is connected to higher insulin levels in adulthood, and higher prenatal exposure to Di-(2-ethyl-hexyl) phthalate (DEHP) and Di-iso-nonyl phthalate (DiNP) metabolites is linked to higher fasting serum glucose levels in adulthood.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Cell Biology
Giulia Avellino, Ruhi Deshmukh, Stephanie N. Rogers, D. Stephen Charnock-Jones, Gordon C. S. Smith, Saverio Tardito, Irving L. M. H. Aye
Summary: Human trophoblast cultures are important for studying placental development. However, current in vitro studies using commercial media with nonphysiological nutrient levels have unknown effects on trophoblast metabolism and function. This study shows that a physiological medium called Plasmax, which mimics human plasma, improves the proliferation and differentiation of human trophoblast stem cells (hTSCs) compared to standard medium (DMEM-F12). hTSCs cultured in Plasmax-based medium also exhibit altered metabolism and reduced S-adenosylmethionine/S-adenosyl-homocysteine ratio. These findings highlight the importance of the nutritional environment for phenotyping cultured human trophoblasts.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Cell Biology
Sungsam Gong, Francesca Gaccioli, Irving L. M. H. Aye, Giulia Avellino, Emma Cook, Andrew R. J. Lawson, Luke M. R. Harvey, Gordon C. S. Smith, D. Stephen Charnock-Jones
Summary: The aim of this study is to identify uniquely absent or depleted transcripts in the placenta, and it is found that 40 out of 46 other organs have no selectively depleted transcripts. The liver has the largest number of depleted transcripts, with 26, while the term placenta has 762 depleted transcripts, including genes involved in mitochondrial function and polyamine metabolism.
Article
Microbiology
Lisa F. Stinson, Yey Berman, Shaofu Li, Jeffrey A. Keelan, Jan E. Dickinson, Dorota A. Doherty, John P. Newnham, Matthew S. Payne
Summary: There is a strong association between intrauterine bacteria and preterm birth. This study investigated the bacterial and cytokine profiles in mid-gestation amniotic fluid samples from Australian preterm and term births. The results showed low diversity and richness in bacterial DNA profiles, with no significant differences between term and preterm samples. Certain cytokine levels were elevated in the presence of specific bacteria, but the biological relevance of this remains unknown.
Article
Obstetrics & Gynecology
Yuki Takahashi, Tsukasa Takahashi, Haruo Usuda, Sean Carter, Erin L. Fee, Lucy Furfaro, Sylvain Chemtob, David M. Olson, Jeffrey A. Keelan, Suhas Kallapur, Matthew W. Kemp
Summary: The study demonstrates that intraamniotic administration of rytvela and anakinra can significantly inhibit inflammation induced by intraamniotic lipopolysaccharide in preterm fetal sheep, protecting the fetal brain.
AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
(2023)
Meeting Abstract
Obstetrics & Gynecology
L. Wijs, D. A. Doherty, J. A. Keelan, B. Penova-Veselinovic, P. Burton, J. L. Yovich, G. L. Hall, P. D. Sly, P. G. Holt, R. J. Hart
HUMAN REPRODUCTION
(2022)
Article
Cell Biology
Karina A. Pena, Sofya Savransky, Breanna Lewis
Summary: Compartmentalization of GPCR signaling is an emerging topic that emphasizes the importance of spatial bias in signaling for physiological relevance. PTH1R was the first GPCR discovered to signal via cAMP from endosomes, challenging the conventional model of GPCR signaling. The location of cAMP generation determines the physiological outcomes of GPCR signaling.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Cheng-Xu Ma, Xiao-Ni Ma, Jin-Jin Liu, Cong-Hui Guan, Ying-Dong Li, Nan Zhao, Didac Mauricio, Song-Bo Fu
Summary: The downregulation of primary cilia (PCs) due to BRAFV600E mutation contributes to the aggressiveness and lymph node metastasis of Papillary Thyroid Cancer (PTC).
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Kejun Wu, Cuihua Huang, Wenrong Zheng, Yubin Wu, Qintao Huang, Menghua Lin, Ruonan Gao, Liqin Qi, Guanlian He, Xiaoying Liu, Xiaohong Liu, Linxi Wang, Zhou Chen, Libin Liu
Summary: Recurrent non-severe hypoglycemia in patients with diabetes is associated with cognitive impairment. This study found that this condition is associated with reduced mitophagy in the hippocampus, leading to mitochondrial dysfunction and neurological impairment.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Yifei Lv, Yizhou Huang, Huiyu Fan, Yunxiu Zhao, Linjuan Ma, Yibing Lan, Chunming Li, Peiqiong Chen, Zheng Lou, Jianhong Zhou
Summary: Before menopause, females have a lower incidence of cardiovascular disease than age-matched males, possibly due to the protective effects of sex hormones. 17 beta-E2 inhibits THBS1 expression, preventing cell senescence and apoptosis, and counteracts oxidative stress by suppressing the TGF-beta/Smad signaling pathway.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Ana C. L. Camargo, Flavia B. Constantino, Sergio A. A. Santos, Ketlin T. Colombelli, Luiz M. F. Portela, Matheus N. Fioretto, Luisa A. Barata, Guilherme T. Valente, Carlos S. Moreno, Luis A. Justulin
Summary: This study examined the effects of maternal malnutrition on the transcriptomic landscape of the ventral prostate in rats. It found that changes in molecular pathways related to cellular development and tissue morphogenesis were associated with maternal malnutrition. The Abcg1 gene was found to be deregulated in both malnourished rats and prostate cancer models and patients.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Sandra Romero-Cordoba, Mayel Chirinos, Nancy Noyola-Martinez, Nayeli Torres-Ramirez, Mitzi Garcia-Olivares, Juan Pablo Aragon-Hernandez, Ixchel Ramirez-Camacho, Rosa Zuniga, Fernando Larrea, Ali Halhali, David Barrera
Summary: This study analyzed the effects of calcitriol, TGF-131, and their combination on human trophoblast cells. The results showed that the combination treatment modified the transcriptional landscape and mainly affected the storage, activity, and metabolism of lipids, which may have an impact on placental development.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Traver J. Wright, Richard B. Pyles, Melinda Sheffield-Moore, Rachel R. Deer, Kathleen M. Randolph, Kristen A. Mcgovern, Christopher P. Danesi, Charles R. Gilkison, Weston W. Ward, Jayson A. Vargas, Peyton A. Armstrong, Sarah E. Lindsay, Mohammed F. Zaidan, Justin Seashore, Tamara L. Wexler, Brent E. Masel, Randall J. Urban
Summary: This study investigates the persistent neurologic symptoms in COVID-19 patients after recovery and explores the association between these symptoms and disrupted growth hormone secretion and gastrointestinal discomfort.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
Article
Cell Biology
Li-Li Chen, Ya-Qin Li, Zhi-Hui Kang, Xuan Zhang, Su-Yan Gu, Na Wang, Xue-Yan Shen
Summary: Defects in trophoblastic EMT caused by dysregulation of circTNRC18's interaction with LIN28A play a vital role in the development of preeclampsia. LIN28A overexpression suppresses circTNRC18-mediated inhibition of trophoblast migration, invasion, and EMT, while LIN28A knockdown promotes them. Furthermore, circTNRC18 regulates the intracellular distribution of LIN28A and the expression of insulin-like growth factor II, affecting cell migration and invasion. Targeting the circTNRC18-LIN28A regulatory axis may provide a novel treatment approach for preeclampsia.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2024)
