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Contemporary Perspectives on Chronic Renal Disorders.

The prevalence of renal diseases and its associated burden on healthcare have tremendously risen in the past few years. From simple markers assessing kidney function, current renal research delves into understanding the diseases at the cellular and molecular levels and not just at treating, but at improving quality of life, arresting progression and providing personalized diagnostics and therapy. This narrative review highlights the improvements in diagnostic applications of kidney disease and briefly discusses a few notable biomarkers emphasizing the high throughput omics technologies, as wel

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… Metabolomics, proteomics, genomics, and lipidomics are examples of high‐throughput omics techniques that are widely being used. These techniques have proven to be successful in developing novel biomarkers that can accurately reflect the complex disease process [ 5 ]. … Lipids Profiling in Kidney Disease Lipidomics has garnered interest in CKD because of the established lipid alterations. The common lipid abnormalities associated with CKD are high triglycerides, VLDL, and low HDL [ 64 ]. …

Spatiotemperal Dynamics of Osteoarthritis: Преобразование значений от стенда до Бедсайда.

Остеоартрит (OA) представляет собой многогранное дегенеративное совместное расстройство, вызванное различными факторами риска, такими, как возраст, механический стресс, воспаление и метаболическое воздействие. Эти элементы способствуют его разнообразным фенотипам и эндотипам, что подчеркивает имманентную сложность болезни. Участие нескольких тканей и их взаимодействие еще больше осложняет расследование ОА. Нынешние ограничения в области технологий пространственного фенотификации в сочетании со сложной сетью многофакторных взаимодействий препятствуют обнаружению надежных ранних диагностических

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… OA : Recent advances in the molecular changes of OA from a spatiotemporal perspective mainly focus on spatial metabolomics and lipidomics. … These findings emphasise the unique lipidomic signature of OA synovium and its potential utility in diagnostic and therapeutic applications [ 206 ]. These investigations provide invaluable insights into OA's complex metabolic and lipidomic adaptations. …

Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine.

Multiple myeloma (MM) is a hematological malignancy worldwide in urgent need for novel therapeutic strategies. Since Velcade (bortezomib) was approved for the treatment of relapsed/refractory MM in 2003, we have seen considerable improvement in extending MM patient survival. However, most patients are fraught with high recurrence rate and incurability. Acupuncture is known for alleviating patient symptoms and improving the quality of life, but it is not well investigated in MM, especially in combination with bortezomib. In this study, we employed LC-MS and UHPLC-MS together with bioinformatics

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… Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics. Int J Mol Sci (2017) 18(12):2550. doi: 10.3390/ijms18122550 28. Colombero C, Cardenas S, Venara M, Martin A, Pennisi P, Barontini M, et al. … Alterations in Arginine and Energy Metabolism, Structural and Signalling Lipids in Metastatic Breast Cancer in Mice Detected in Plasma by Targeted Metabolomics and Lipidomics. Breast Cancer Res (2018) 20(1):148. doi: 10.1186/s13058-018-1075-y 46. Du T, Han J. …

Short-chain fatty acids in the tumor microenvironment: from molecular mechanisms to cancer therapy.

Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, serve as pivotal metabolites within the tumor microenvironment (TME), playing essential roles in modulating tumor progression. Although the biological functions and mechanisms of SCFAs in the TME show some overlap, each SCFA also exerts some distinct regulatory effects on tumors and TME. Notably, even a single SCFA may exhibit pleiotropic effects across different cancer types or under varying conditions within the same malignancy. Consequently, according to the different metabolic microenvironment of patients, precis

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… However, advances in lipidomics have deepened our understanding of lipid functionality 14 - 16 . As the basic skeleton of lipids, fatty acids (FAs) exert diverse biological effects in the TME 17 , 18 . … 'Lipidomics': Mass spectrometric and chemometric analyses of lipids. Adv Drug Deliv Rev. 2020;159:294–307. doi: 10.1016/j.addr.2020.06.009. 15. Jensen M, Liu S, Stepula E, Martella D, Birjandi AA, Farrell-Dillon K. et al. Opto-Lipidomics of Tissues. …

Role of exosomes in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies. Exosomes, which are released by multiple cell types, such as cancer cells, contain functional biomolecules (including proteins, nucleic acids and lipids) that can be horizontally delivered to recipient cells. Exosomes act as the most prominent mediator of intercellular communication and can regulate, instruct and re-educate their surrounding microenvironment and target specific organs. The present review performed an extensive search of multiple databases from 2005 to April 23 2017, for eligible literature relating to exosomes and their

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… It is possible that progress in lipidomics will aid in the improved understanding of the biological mechanisms of exosomal formation, sorting and release under physiological and pathological conditions. … Lombardo D Exosomal lipids induce human pancreatic tumoral MiaPaCa-2 cells resistance through the CXCR4-SDF-1α signaling axis Oncoscience 2 15 30 2014 25821841 10.18632/oncoscience.96 PMC4341461 19 Llorente A Skotland T Sylvänne T Kauhanen D Róg T Orłowski A Vattulainen I Ekroos K Sandvig K Molecular lipidomics …

Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress.

The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER st

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… Sphingolipidomics Quantitation of sphingolipid species was performed at the Lipidomics Core Facility, Medical University of South Carolina, using previously described methods [ 52 ]. Proliferation and viability assays Cell proliferation was measured using the WST-1 reagent (Sigma-Aldrich). … We also acknowledge Prof Jacek Bielawski (Lipidomics Mass Spectrometry Unit, Medical University of South Carolina) for performing the sphingolipid mass spectrometry, Dr John Toubia (University of South Australia and SA Pathology) for assistance with gene set enrichment analysis and the staff of the SA …

Ganglioside therapy in cancer molecular insights and therapeutic opportunities.

Gangliosides, a class of glycosphingolipids located on the plasma membrane of nearly all cells, play a crucial role in cell signaling and lipid raft dynamics. Their expression is notably high during embryonic development, markedly reduced in most adult tissues, but significantly elevated in various tumor tissues. This distinct expression pattern highlights gangliosides as promising therapeutic targets due to their roles in tumor progression, metastasis, and therapeutic resistance. Targeted ganglioside therapies, particularly monoclonal antibodies against GD2, have already demonstrated clinical

Disease-Modifying Therapies for Multiple System Atrophy: Where Are We in 2022?

Multiple system atrophy is a rapidly progressive and fatal neurodegenerative disorder. While numerous preclinical studies suggested efficacy of potentially disease modifying agents, none of those were proven to be effective in large-scale clinical trials. Three major strategies are currently pursued in preclinical and clinical studies attempting to slow down disease progression. These target α-synuclein, neuroinflammation, and restoration of neurotrophic support. This review provides a comprehensive overview on ongoing preclinical and clinical developments of disease modifying therapies. Furth

Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.

Bortezomib, a first-generation proteasome inhibitor widely used in chemotherapy for hematologic malignancy, has effective anti-cancer activity but often causes severe peripheral neuropathy. Although bortezomib-induced peripheral neuropathy (BIPN) is a dose-limiting toxicity, there are no recommended therapeutics for its prevention or treatment. One of the most critical problems is a lack of knowledge about pathological mechanisms of BIPN. Here, we summarize the known mechanisms of BIPN based on preclinical evidence, including morphological abnormalities, involvement of non-neuronal cells, oxid

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… Recently, lipidomics analysis of serum from 59 patients identified certain lipid species as biomarker candidates of BIPN symptoms [ 89 ]. … Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma. Cancer Sci. 2019;110:3267–3274. doi: 10.1111/cas.14178. …

ISEV2025 Резюме книги.

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Metabolic reprogramming in T cell senescence: a novel strategy for cancer immunotherapy.

The complex interplay between cancer progression and immune senescence is critically influenced by metabolic reprogramming in T cells. As T cells age, especially within the tumor microenvironment, they undergo significant metabolic shifts that may hinder their proliferation and functionality. This manuscript reviews how metabolic alterations contribute to T cell senescence in cancer and discusses potential therapeutic strategies aimed at reversing these metabolic changes. We explore interventions such as mitochondrial enhancement, glycolytic inhibition, and lipid metabolism adjustments that co

Idiopathic pulmonary fibrosis: Current and future treatment.

ObjectivesIdiopathic pulmonary fibrosis (IPF) is a chronic fibrotic lung disease characterized by dry cough, fatigue, and progressive exertional dyspnea. Lung parenchyma and architecture is destroyed, compliance is lost, and gas exchange is compromised in this debilitating condition that leads inexorably to respiratory failure and death within 3-5 years of diagnosis. This review discusses treatment approaches to IPF in current use and those that appear promising for future development.Data sourceThe data were obtained from the Randomized Controlled Trials and scientific studies published in En

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… Gene and protein expression profiling is beginning to generate information on the mechanisms that result in lung damage in IPF. 155 , 156 Lipidomics are also being analyzed to expand our knowledge of how IPF progresses. 157 The clinical and research communities must come together to find better ways … There is detectable variation in the lipidomic profile between stable and progressive patients with idiopathic pulmonary fibrosis (IPF) . Respir Res . 2021 ; 22 : 105 . 33836757 10.1186/s12931-021-01682-3 PMC8033725 …

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

Hematological Malignancy-Derived Small Extracellular Vesicles and Tumor Microenvironment: The Art of Turning Foes into Friends.

Small extracellular vesicles (small EVs) are commonly released by all cells, and are found in all body fluids. They are implicated in cell to cell short- and long-distance communication through the transfer of genetic material and proteins, as well as interactions between target cell membrane receptors and ligands anchored on small EV membrane. Beyond their canonical functions in healthy tissues, small EVs are strategically used by tumors to communicate with the cellular microenvironment and to establish a proper niche which would ultimately allow cancer cell proliferation, escape from the imm

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

Менделийский анализ случайности не подтверждает причинно-следственного воздействия липопротеинов (А) и иммунопосредованных подстрекательских заболеваний.

Результаты наблюдений свидетельствуют о наличии связи между липопротеином(a) (Lp(a)) и эпидемическими эпидемическими заболеваниями (IMID). Для изучения причинно-следственной связи между липопротеином (a) [Lp(a)] и иммунизированными подстрекательскими заболеваниями (IMID) в этом исследовании использовались менделианские методы рандомизации (MR) и многовариантные MR (MVMR). Мы провели двухнаправленный анализ менделизации с использованием двух выборок на основе общих исследований генома (GWAS) сводные статистические данные по Lp(a) и девяти IMID, в частности по заболеваниям селияка (CeD), болезни

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… In the future, by including more lipid characteristics and analyzing their relationship with inflammation-related diseases through lipidomics and other methods, it will provide more understanding of the relationship between lipid disorders and inflammation-related diseases. …

Количественная оценка холестерина в мозговой и спинной кордах во время развития, обезвоживания и ремиелинации.

Хлестерин в центральной нервной системе (КНС) в значительной степени неэстерифицирован (>99%) и присутствует главным образом в миелинской оболочке (~70% от общего количества холестерина CNS). Однако во время неврологических заболеваний наблюдалось накопление холестерина. В этом поперечном исследовании мы измерили уровень свободного холестерина и холестерина эстера в мозгу и спинные мозги модели мыши Plp1-iCKO-Myrf во время послеродовой миелиации, демиелинации и ремиелиции с использованием газовой хроматографии-массы спектрометрии с одним ионным мониторингом (GC-MS-SIM) и жидкой хроматографии-м

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… Although lipidomics studies on CNS tissues are becoming more common, it remains challenging to accurately quantify cholesterol and related sterols using mass spectrometry methods reliant on electrospray ionization (ESI) as cholesterol does not ionize well under ESI conditions. … Lipidomic analysis reveals differences in the extent of remyelination in the brain and spinal cord J. Proteome Res. 2023 23 2830 2844 10.1021/acs.jproteome.3c00443 38018851 PMC11133230 24. Zupan M.C. Petersen J.M. Stover A.C. Fairchild C.A. Mohotti N.D.S. Hartley M.D. …

Hypothesis: are neoplastic macrophages/microglia present in glioblastoma multiforme?

Most malignant brain tumours contain various numbers of cells with characteristics of activated or dysmorphic macrophages/microglia. These cells are generally considered part of the tumour stroma and are often described as TAM (tumour-associated macrophages). These types of cells are thought to either enhance or inhibit brain tumour progression. Recent evidence indicates that neoplastic cells with macrophage characteristics are found in numerous metastatic cancers of non-CNS (central nervous system) origin. Evidence is presented here suggesting that subpopulations of cells within human gliomas

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease.

Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as ev

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… Full Original Lipidomics Data are available in Supplementary Data 1 . To investigate whether exogenous GlcCer or LacCer may be sufficient to rescue eliglustat-induced autophagy deficiency, three commercially available lipids, LacCer (C16 and C24), and GlcCer (C16), were investigated. … Full Original Lipidomics Data is available in Supplementary Data 1 . Statistical analyses All data shown are represented as mean ± standard error of the mean (SEM). Two-tailed t -test was applied when comparing two experimental groups. …

Adipocyte-Tumor Interactions in the Bone Marrow Niche: Implications for Metastasis and Therapy.

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidat

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… Dynamic Lipidomics Current knowledge of BMA lipid metabolism is largely derived from static snapshots. Real-time lipid tracing, particularly in patients, is critically lacking. … Innovative metabolic flux approaches, such as stable isotope–based tracing combined with advanced lipidomics, could clarify how BMAs contribute to tumor lipid acquisition, systemic lipid pools, and energy balance. …