Diabetes mellitus (DM) is a global health concern characterized by a deficiency in insulin production. Considering the systemic toxicity and limited efficacy associated with current antidiabetic medications, there is the utmost need for natural, plant-based alternatives. Herbal medicines have experienced exponential growth in popularity globally in recent years for their natural origins and minimal side effects. Ecuador has a rich cultural history in ethnobotany that plays a crucial role in its people's lives. This study identifies 27 Ecuadorian medicinal plants that are traditionally used for diabetes treatment and are prepared through infusion, decoction, or juice, or are ingested in their raw forms. Among them, 22 plants have demonstrated hypoglycemic or anti-hyperglycemic properties that are rich with bioactive phytochemicals, which was confirmed in several in vitro and in vivo studies. However, Bryophyllum gastonis-bonnieri, Costus villosissimus, Juglans neotropica, Pithecellobium excelsum, and Myroxylon peruiferum, which were extensively used in traditional medicine preparation in Ecuador for many decades to treat diabetes, are lacking in pharmacological elucidation. The Ecuadorian medicinal plants used to treat diabetes have been found to have several bioactive compounds such as flavonoids, phenolics, fatty acids, aldehydes, and terpenoids that are mainly responsible for reducing blood sugar levels and oxidative stress, regulating intestinal function, improving insulin resistance, inhibiting α-amylase and α-glucosidase, lowering gluconeogenic enzymes, stimulating glucose uptake mechanisms, and playing an important role in glucose and lipid metabolism. However, there is a substantial lack of integrated approaches between the existing ethnomedicinal practices and pharmacological research. Therefore, this review aims to discuss and explore the traditional medicinal plants used in Ecuador for treating DM and their bioactive phytochemicals, which are mainly responsible for their antidiabetic properties. We believe that the use of Ecuadorian herbal medicine in a scientifically sound way can substantially benefit the local economy and industries seeking natural products.

• Publication type
• Journal Article MeSH
• Review MeSH

Menopause brings about profound physiological changes, including the acceleration of insulin resistance and other abnormalities, in which adipose tissue can play a significant role. This study analyzed the effect of ovariectomy and estradiol substitution on the metabolic parameters and transcriptomic profile of adipose tissue in prediabetic females of hereditary hypertriglyceridemic rats (HHTgs). The HHTgs underwent ovariectomy (OVX) or sham surgery (SHAM), and half of the OVX group received 17β-estradiol (OVX+E2) post-surgery. Ovariectomy resulted in weight gain, an impaired glucose tolerance, ectopic triglyceride (TG) deposition, and insulin resistance exemplified by impaired glycogenesis and lipogenesis. Estradiol alleviated some of the disorders associated with ovariectomy; in particular, it improved insulin sensitivity and reduced TG deposition. A transcriptomic analysis of perimetrial adipose tissue revealed 809 differentially expressed transcripts in the OVX vs. SHAM groups, mostly pertaining to the regulation of lipid and glucose metabolism, and oxidative stress. Estradiol substitution affected 1049 transcripts with overrepresentation in the signaling pathways of lipid metabolism. The principal component and hierarchical clustering analyses of transcriptome shifts corroborated the metabolic data, showing a closer resemblance between the OVX+E2 and SHAM groups compared to the OVX group. Changes in the adipose tissue transcriptome may contribute to metabolic abnormalities accompanying ovariectomy-induced menopause in HHTg females. Estradiol substitution may partially mitigate some of these disorders.

• Publication type
• Journal Article MeSH

• MeSH
• Adaptation, Biological MeSH
• Exercise * physiology   MeSH
• Energy Metabolism physiology   MeSH
• Muscle Fibers, Skeletal physiology   metabolism   MeSH
• Humans MeSH
• Lipid Metabolism MeSH
• Carbohydrate Metabolism MeSH
• Oxidative Phosphorylation MeSH
• Physical Exertion physiology   MeSH
• Physical Fitness physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

• MeSH
• Exercise MeSH
• Sports Nutritional Physiological Phenomena * MeSH
• Nutritional Physiological Phenomena MeSH
• Glycemic Index MeSH
• Humans MeSH
• Lipids MeSH
• Drinking physiology   MeSH
• Dietary Supplements MeSH
• Dietary Fiber MeSH
• Proteins MeSH
• Carbohydrates MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Digital weight loss interventions present a viable and cost-effective alternative to traditional therapy. However, further evidence is needed to establish the equal effectiveness of both approaches. This randomized controlled non-inferiority trial aimed to compare the effects of an intensive in-person weight loss intervention program with Vitadio digital therapy. One hundred patients with obesity and diagnosed with type 2 diabetes, prediabetes, or insulin resistance were enrolled and randomly assigned to one of the two treatment groups. Over a 6-month period, the control group received five in-person consultations with a physician who specialized in obesity treatment, a dietitian and/or a nutrition nurse, while the intervention group followed the digital program based on a multimodal therapeutic approach. The extent of weight loss was assessed and compared between the groups. Additionally, changes in body composition and metabolic parameters for the digital intervention group were analyzed. The study results demonstrated comparable effectiveness of both treatments for weight reduction. The positive effects of Vitadio were further evidenced by favorable changes in body composition and lipid metabolism and improved glycemic control in the intervention group. These findings suggest that Vitadio is an effective tool for assisting patients with managing obesity and preventing diabetes progression.

• MeSH
• Diabetes Mellitus, Type 2 * therapy   MeSH
• Adult MeSH
• Weight Loss * MeSH
• Insulin Resistance MeSH
• Blood Glucose metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity * therapy   MeSH
• Prediabetic State * therapy   MeSH
• Weight Reduction Programs * methods   MeSH
• Body Composition MeSH
• Telemedicine MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

Acylcarnitines are important markers in metabolic studies of many diseases, including metabolic, cardiovascular, and neurological disorders. We reviewed analytical methods for analyzing acylcarnitines with respect to the available molecular structural information, the technical limitations of legacy methods, and the potential of new mass spectrometry-based techniques to provide new information on metabolite structure. We summarized the nomenclature of acylcarnitines based on historical common names and common abbreviations, and we propose the use of systematic abbreviations derived from the shorthand notation for lipid structures. The transition to systematic nomenclature will facilitate acylcarnitine annotation, reporting, and standardization in metabolomics. We have reviewed the metabolic origins of acylcarnitines important for the biological interpretation of human metabolomic profiles. We identified neglected isomers of acylcarnitines and summarized the metabolic pathways involved in the synthesis and degradation of acylcarnitines, including branched-chain lipids and amino acids. We reviewed the primary literature, mapped the metabolic transformations of acyl-CoAs to acylcarnitines, and created a freely available WikiPathway WP5423 to help researchers navigate the acylcarnitine field. The WikiPathway was curated, metabolites and metabolic reactions were annotated, and references were included. We also provide a table for conversion between common names and abbreviations and systematic abbreviations linked to the LIPID MAPS or Human Metabolome Database.

• MeSH
• Carnitine * analogs & derivatives   metabolism   biosynthesis   MeSH
• Humans MeSH
• Metabolic Networks and Pathways * MeSH
• Metabolomics MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Cylindrospermopsin, a potent hepatotoxin produced by harmful cyanobacterial blooms, poses environmental and human health concerns. We used a 3D human liver in vitro model based on spheroids of HepG2 cells, in combination with molecular and biochemical assays, automated imaging, targeted LC-MS-based proteomics, and lipidomics, to explore cylindrospermopsin effects on lipid metabolism and the processes implicated in hepatic steatosis. Cylindrospermopsin (1 μM, 48 h) did not significantly affect cell viability but partially reduced albumin secretion. However, it increased neutral lipid accumulation in HepG2 spheroids while decreasing phospholipid levels. Simultaneously, cylindrospermopsin upregulated genes for lipogenesis regulation (SREBF1) and triacylglycerol synthesis (DGAT1/2) and downregulated genes for fatty acid synthesis (ACLY, ACCA, FASN, SCD1). Fatty acid uptake, oxidation, and lipid efflux genes were not significantly affected. Targeted proteomics revealed increased levels of perilipin 2 (adipophilin), a major hepatocyte lipid droplet-associated protein. Lipid profiling quantified 246 lipid species in the spheroids, with 28 significantly enriched and 15 downregulated by cylindrospermopsin. Upregulated species included neutral lipids, sphingolipids (e.g., ceramides and dihexosylceramides), and some glycerophospholipids (phosphatidylethanolamines, phosphatidylserines), while phosphatidylcholines and phosphatidylinositols were mostly reduced. It suggests that cylindrospermopsin exposures might contribute to developing and progressing towards hepatic steatosis or metabolic dysfunction-associated steatotic liver disease (MASLD).

• MeSH
• Alkaloids * pharmacology   MeSH
• Bacterial Toxins * metabolism   MeSH
• Spheroids, Cellular drug effects   metabolism   MeSH
• Hep G2 Cells MeSH
• Homeostasis drug effects   MeSH
• Liver * metabolism   drug effects   MeSH
• Humans MeSH
• Lipidomics MeSH
• Lipogenesis drug effects   MeSH
• Lipid Metabolism * drug effects   MeSH
• Proteomics MeSH
• Cyanobacteria Toxins * MeSH
• Uracil * analogs & derivatives   metabolism   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

A tumour suppressor miRNA, miR-128-3p, is widely involved in various biological processes and has been found to get downregulated in breast cancer patients. We previously published that ectopically expressed miR-128-3p suppressed migration, invasion, cell cycle arrest, and breast cancer stem cells. In the present study, we explored the role of Empagliflozin (EMPA) as a miR-128-3p functionality-mimicking drug in inducing ferroptosis by inhibiting CD98hc. Given that CD98hc is one of the proteins critical in triggering ferroptosis, we confirmed that miR-128-3p and EMPA inhibited SP1, leading to inhibition of CD98hc expression. Further, transfection with siCD98hc, miR-128-3p mimics, and inhibitors was performed to assess their involvement in the ferroptosis of anoikis-resistant cells. We proved that anoikis-resistant cells possess high ROS and iron levels. Further, miR-128-3p and EMPA treatments induced ferroptosis by inhibiting GSH and enzymatic activity of GPX4 and also induced lipid peroxidation. Moreover, EMPA suppressed bioluminescence of 4T1-Red-FLuc induced thoracic cavity, peritoneal tumour burden and lung nodules in an in-vivo metastatic model of breast cancer. Collectively, we revealed that EMPA sensitized the ECM detached cells to ferroptosis by synergically activating miR-128-3p and lowering the levels of SP1 and CD98hc, making it a potential adjunct drug for breast cancer chemotherapy.

• MeSH
• Anoikis * drug effects   genetics   MeSH
• Benzhydryl Compounds * pharmacology   MeSH
• Ferroptosis * drug effects   genetics   MeSH
• Sodium-Glucose Transporter 2 Inhibitors pharmacology   MeSH
• Glucosides * pharmacology   MeSH
• Sodium-Phosphate Cotransporter Proteins, Type IIb MeSH
• Humans MeSH
• MicroRNAs * genetics   metabolism   MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Breast Neoplasms * pathology   metabolism   drug therapy   genetics   MeSH
• Lipid Peroxidation drug effects   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Gene Expression Regulation, Neoplastic * drug effects   MeSH
• Xenograft Model Antitumor Assays MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The recognition that rapidly proliferating cancer cells rely heavily on glutamine for their survival and growth has renewed interest in the development of glutamine antagonists for cancer therapy. Glutamine plays a pivotal role as a carbon source for synthesizing lipids and metabolites through the TCA cycle, as well as a nitrogen source for synthesis of amino acid and nucleotides. Numerous studies have explored the significance of glutamine metabolism in cancer, providing a robust rationale for targeting this metabolic pathway in cancer treatment. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) has been explored as an anticancer therapeutic for nearly six decades. Initial investigations revealed remarkable efficacy in preclinical studies and promising outcomes in early clinical trials. However, further advancement of DON was hindered due to dose-limiting gastrointestinal (GI) toxicities as the GI system is highly dependent on glutamine for regulating growth and repair. In an effort to repurpose DON and mitigate gastrointestinal (GI) toxicity concerns, prodrug strategies were utilized. These strategies aimed to enhance the delivery of DON to specific target tissues, such as tumors and the central nervous system (CNS), while sparing DON delivery to normal tissues, particularly the GI tract. When administered at low daily doses, optimized for metabolic inhibition, these prodrugs exhibit remarkable effectiveness without inducing significant toxicity to normal tissues. This approach holds promise for overcoming past challenges associated with DON, offering an avenue for its successful utilization in cancer treatment.

• MeSH
• Diazooxonorleucine * pharmacology   therapeutic use   MeSH
• Glutamine metabolism   MeSH
• Humans MeSH
• Neoplasms * drug therapy   metabolism   MeSH
• Prodrugs * pharmacology   therapeutic use   MeSH
• Antineoplastic Agents pharmacology   therapeutic use   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

BACKGROUND: Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events. AIM: We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque. METHODS: This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques. RESULTS: The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification. CONCLUSIONS: Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.

• MeSH
• Plaque, Atherosclerotic * blood   MeSH
• Biomarkers * blood   MeSH
• Chromatography, Liquid MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipidomics * MeSH
• Lipids * blood   MeSH
• Carotid Artery Diseases * blood   diagnosis   MeSH
• Predictive Value of Tests MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Rupture, Spontaneous MeSH
• Case-Control Studies MeSH
• Tandem Mass Spectrometry * MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH