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Can Hemp Help? Low-THC Cannabis and Non-THC Cannabinoids for the Treatment of Cancer.

Cannabis has been used to relieve the symptoms of disease for thousands of years. However, social and political biases have limited effective interrogation of the potential benefits of cannabis and polarised public opinion. Further, the medicinal and clinical utility of cannabis is limited by the psychotropic side effects of ∆9-tetrahydrocannabinol (∆9-THC). Evidence is emerging for the therapeutic benefits of cannabis in the treatment of neurological and neurodegenerative diseases, with potential efficacy as an analgesic and antiemetic for the management of cancer-related pain and treatment-r

Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation.

The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increa

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… Endogenous cannabinoids play a significant role in regulating the de novo synthesis of ceramides (lipid-based components of the phospholipid bilayer involved in structure and cellular signaling). Also, ceramide autophagy has a crucial role in signaling regarding the control of apoptosis. … The link between ceramide signaling (by involving cannabinoids) and some cancers is becoming ever more prevalent in the research to alter tumor microenvironment for cell apoptosis. 55 In glioma cells, either CB1 or CB2 is related to increased ceramide levels. …

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

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… This might explain why overall ceramide levels decrease in aging T cells, yet the levels of specific C14/C16 ceramides are upregulated. Future research should further analyze which ceramides are downregulated and identify the related molecular mechanisms. … Aging-dependent mitochondrial dysfunction mediated by ceramide signaling inhibits antitumor T cell response. Cell Rep. 2021;35:109076. 48. Park JW, Park WJ, Futerman AH. Ceramide synthases as potential targets for therapeutic intervention in human diseases. …

Effect of PLA2G6 and SMPD1 Variants on the Lipid Metabolism in the Cerebrospinal Fluid of Patients with Parkinson's Disease: A Non-targeted Lipidomics Study.

IntroductionSleep patterns are more frequently interrupted in patients with Parkinson's disease (PD), and it is still unclear whether genetic factors are involved in PD-related sleep disorders. In this study, we hypothesize that PD-associated genetic risk affects lipid metabolism, which in turn contributes to different types of sleep disorders.MethodsWe used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations.ResultsPLA2G

Restoration of NK T cell development in fyn-mutant mice by a TCR reveals a requirement for Fyn during early NK T cell ontogeny.

NK T cells are a unique lymphocyte population that have developmental requirements distinct from conventional T cells. Mice lacking the tyrosine kinase Fyn have 5- to 10-fold fewer mature NK T cells. This study shows that Fyn-deficient mice have decreased numbers of NK1.1(-) NK T cell progenitors as well. 5-Bromo-2'-deoxyuridine-labeling studies indicate that the NK T cells remaining in fyn(-/-) mice exhibit a similar turnover rate as wild-type cells. The fyn(-/-) NK T cells respond to alpha-galactosylceramide, a ligand recognized by NK T cells, and produce cytokines, but have depressed prolif

Intracellular and extracellular miRNome deregulation in cellular models of NAFLD or NASH: Clinical implications.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in industrialized countries. NAFLD has the potential to progress through the inflammatory phase of nonalcoholic steatohepatitis (NASH) to fibrosis, cirrhosis, and hepatocellular carcinoma. Identifying patients at risk for this transition is a relevant clinical challenge. The complexity of these phenotypes in vivo made necessary the development of in vitro models in order to dissect the molecular signalling affected in NAFLD and NASH, but also to identify potential circulating biomarkers

Lysosomal storage diseases.

Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage ca

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… In these diseases ( Table 5 ), a variety of lipids can be stored, including ceramides, cerebroside and other ceramide hexosides, sulfatides, sphingomyelins, gangliosides and lipofuscins. Fig.2 Structure of sphingolipids. Sphingosine (top) plus a fatty acid forms ceramide (middle). … Ceramide attached to a single sugar forms a glucocerebroside (bottom). If ceramide is combined with a polysaccharide (complex sugar) with one or more terminal N-acetylneuraminic acids, the result is a ganglioside. …

Устранение неврологических расстройств путем борьбы с нейродегенеративными ассоциированными ферментами: естественные и синтетические молекулы.

Неврологические расстройства, включая нейродегенеративные и нейро-воспалительные заболевания, создают значительные проблемы в области здравоохранения и клинических проблем. Недавние исследования показали, что различные ферменты играют ключевую роль в наступлении и развитии этих расстройств. В этом обзоре изучается терапевтический потенциал адресации этих ферментов естественными и синтетическими молекулами. К таким заболеваниям, как болезнь Альцгеймера, болезнь Паркинсона и множественный склероз, причастны основные ферменты, включая ацетилхолинестеразу, оксидазу моноамина, бета-секретазу, тау к

Dysregulation of sphingolipid metabolism contributes to bortezomib-induced neuropathic pain.

The development of chemotherapy-induced painful peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutics, including bortezomib, but the mechanisms remain poorly understood. We now report that bortezomib causes the dysregulation of de novo sphingolipid metabolism in the spinal cord dorsal horn to increase the levels of sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) ligands, S1P and dihydro-S1P. Accordingly, genetic and pharmacological disruption of S1PR1 with multiple S1PR1 antagonists, including FTY720, blocked and reversed neuropathic pain. Mice with astrocyte-sp

Cannabis Biomolecule Effects on Cancer Cells and Cancer Stem Cells: Cytotoxic, Anti-Proliferative, and Anti-Migratory Activities.

Cancer is a complex family of diseases affecting millions of people worldwide. Gliomas are primary brain tumors that account for ~80% of all malignant brain tumors. Glioblastoma multiforme (GBM) is the most common, invasive, and lethal subtype of glioma. Therapy resistance and intra-GBM tumoral heterogeneity are promoted by subpopulations of glioma stem cells (GSCs). Cannabis sativa produces hundreds of secondary metabolites, such as flavonoids, terpenes, and phytocannabinoids. Around 160 phytocannabinoids have been identified in C. sativa. Cannabis is commonly used to treat various medical co

Влияние различных методов лечения на толщину спины у пациентов с множественным склерозом: обзор.

Множественный склероз (MS) — аутоиммунное расстройство, воздействующее на центральную нервную систему с различными клиническими проявлениями, такими, как оптический неврит, сенсорные расстройства и синдромы головного мозга. Происхождение заболеваний контролируется с помощью таких методов, как сканирование МРТ, шкала инвалидности и томография оптической согласованности (OCT), которые могут обнаруживать утончённую сетчатку сетчатки, даже при отсутствии оптического невраита. MS прогрессирует в нейродегенерации, особенно транссинптической дегенерации, которая выходит за рамки первоначального места

Fatty acid synthase in chemoresistance: mechanisms and therapeutic opportunities.

Chemoresistance has been a major obstacle to the efficient treatment of cancer. Recently, targeting lipid metabolism has gained significant attention because of its roles not only in promoting cancer progression but also in inducing chemotherapy resistance. Fatty acid synthase (FAS) is the sole enzyme that is in charge of catalyzing the synthesis of palmitate, a long-chain lipid that is essential for membrane construction and post-translational modification in cell biology. Both FAS and its product, palmitate, have been validated as critical players in mediating or causing chemoresistance in c

Molecular Mechanism of Autophagy and Its Regulation by Cannabinoids in Cancer.

Autophagy is a "self-degradation" process whereby malfunctioned cytoplasmic constituents and protein aggregates are engulfed by a vesicle called the autophagosome, and subsequently degraded by the lysosome. Autophagy plays a crucial role in sustaining protein homeostasis and can be an alternative source of energy under detrimental circumstances. Studies have demonstrated a paradoxical function for autophagy in cancer, displaying both tumour suppressive and tumour promotive roles. In early phases of tumour development autophagy promotes cancer cell death. In later phases, autophagy enables canc

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t

Липид Метаболизм и статинская терапия нейродегенеративных заболеваний: эндокринный взгляд.

Справочная информация/цели: Растущий объем данных свидетельствует о наличии связи между дислипидемией и нейродегенеративными заболеваниями, подчеркивая решающую роль липидного метаболизма в здоровье центральной нервной системы. Цель нашей работы состояла в том, чтобы представить обновленную информацию по этой теме с уделением особого внимания клинической практике с эндокринологической точки зрения. Эндокринологи, будучи экспертами в области управления дислипидемиями, могут играть ключевую роль в профилактике и лечении нейродегенеративных заболеваний путем предварительной и эффективной оптимиза

Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

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… Ceramides are bioactive sphingolipids generated de novo by ceramide synthetase (Ces 1–6), containing fatty acids of various lengths. The type of fatty acyl group that is attached often dictates the biological activity of ceramide. … Mitochondrial C 18 -ceramide interacted with LC3B-II to recruit autophagosomes to mitochondria for degradation via the ceramide-binding domain. Additionally, AML can upregulate ceramide catabolism through acid ceramidase (AC) overexpression [ 155 ]. …

Use of Cannabis and Cannabinoids for Treatment of Cancer.

The endocannabinoid system (ECS) is an ancient homeostasis mechanism operating from embryonic stages to adulthood. It controls the growth and development of many cells and cell lineages. Dysregulation of the components of the ECS may result in uncontrolled proliferation, adhesion, invasion, inhibition of apoptosis and increased vascularization, leading to the development of various malignancies. Cancer is the disease of uncontrolled cell division. In this review, we will discuss whether the changes to the ECS are a cause or a consequence of malignization and whether different tissues react dif

Оценка причинно-следственного воздействия метаболомы на риск психических и нейродегенеративных расстройств.

Данные свидетельствуют о фенотипическом и биологическом переплетении между психическими и нейродегенеративными расстройствами. Дальнейшее выявление лежащих в основе взаимных и уникальных биологических механизмов может привести к появлению новых, многопорядковых и многопорядковых терапевтических целей. Метаболом представляет собой важную область для идентификации целей, поскольку метаболиты играют важнейшую роль в модуляции разнообразных биологических процессов.Мы использовали менделианскую случайность (MR) для проверки причинного воздействия ~ 1000 плазменных метаболитов и ~ 300 метаболитов на

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… Sphingomyelins are central to ceramide metabolism, to which they are converted via sphingomyelinase and back via sphingomyelin synthase [ 117 ] (Additional File 1: Fig S5). Ceramides are catabolised into sphingosine and eventually sphingosine-1-phosphate [ 117 ]. … As such, the ceramide system is a proposed pathway for drug-based interventions for psychiatric disorders [ 117 ]. This study implicates sphingomyelins as possible protective targets. …

Gaucher disease: clinical profile and therapeutic developments.

Gaucher disease is a rare inborn error of glycosphingolipid metabolism due to deficiency of lysosomal acid β-glucocerebrosidase; the condition has totemic significance for the development of orphan drugs. A designer therapy, which harnesses the mannose receptor to complement the functional defect in macrophages, ameliorates the principal clinical manifestations in hematopoietic bone marrow and viscera. While several aspects of Gaucher disease (particularly those affecting the skeleton and brain) are refractory to treatment, enzyme (replacement) therapy has become a pharmaceutical blockbuster.

Перепрофилированный активатор Nrf2 диметилфумарат спасает мышцы воспаление и фиброз в отягченной мышиной модели мышечной дистрофии Дученна.

В унаследованных нейромускульных болезнях мышечная дистрофия Дюченна (ДМД) глюкокортикоиды значительно медленнее прогрессируют, но в то же время создают достаточно серьезные побочные эффекты, исключающие применение в значительной части пациентов. Распространяя наши выводы о том, что в результате острого лечения с УЛХ были одобрены многочисленные склерозные препараты, диметилфумарат (ДМФ), спасающая мышечную патологию у молодых мышей Mdx, мы намеревались провести доклиническое тестирование на перевод. Чтобы усилить фенотип болезни у взрослых мышц mdx, у которых обычно нет эквивалентной человече

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… Reactome pathway analysis ( Supplemental Table 3 ) revealed that the tumour necrosis factor receptor (TNFR)-mediated ceramide production pathway was significantly upregulated in mdx quadriceps and was normalised by DMF but not PRED treatment. … In humans, TNFR1 agonism contributes to muscle adiposis by inducing sphingomyelin hydrolysis-mediated ceramide production. Ceramides are bioactive molecules capable of activating apoptotic and pro-inflammatory pathways and their accumulation in muscle is linked to myopathy [ 48 ]. …