Julia Siemińska

Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a major public health concern. The pediatric form of MASLD differs from the adult phenotype in its pathophysiology and exhibits distinct histopathological characteristics. This study aimed to characterize serum metabolomic alterations associated with pediatric MASLD and to identify metabolic signatures that may provide further insight into the disease phenotype. To this end, untargeted metabolomic analysis was performed on serum samples from 21 pediatric MASLD patients and 22 healthy controls using liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry (LC-MS/QTOF). Univariate statistical analysis was performed using the Mann–Whitney U-test with false discovery rate (FDR) correction, while multivariate analysis employed principal component analysis and orthogonal partial least squares discriminant analysis (OPLS-DA). Multivariate analysis in the positive ionization mode demonstrated clear separation between the MASLD and control groups (R²Y = 0.972, Q² = 0.823, CV-ANOVA p-value = 2.387 × 10⁻¹⁰). A total of 46 annotated metabolites differed significantly between the groups. The most pronounced alterations involved bile acid and sterol metabolism, including increased 12α-hydroxy-3-oxocholadienic acid and decreased conjugated primary bile acids, including taurine and glycine conjugates. In addition, increased levels of free carnitine and short-chain acylcarnitines, together with alterations in free and oxidized fatty acids, suggested disturbances in fatty acid metabolism. The metabolomic profile also revealed broad disruption of glycerophospholipid metabolism, characterized primarily by decreased lysophosphatidylcholines and lysophosphatidylethanolamines. In conclusion, the metabolomic profile of pediatric MASLD indicates pronounced systemic metabolic alterations, primarily involving lipid and fatty acid metabolism, bile acid and sterol metabolism, and amino acid-related pathways. The coordinated pattern of these changes suggests alterations across multiple interconnected metabolic processes, highlighting the complex metabolic phenotype of pediatric MASLD. The identified metabolic signatures provide a basis for further investigation and warrant validation in larger, independent cohorts to determine their biological and potential clinical relevance.

Phloroglucinol (PHG), an analgesic and spasmolytic drug, shows promise in preventing high-fat-diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. In Wistar rats, 10 weeks of PHG treatment did not prevent HFD-induced weight gain but significantly mitigated fasting hyperglycemia, impaired insulin responses, and liver steatosis. This protective effect was not linked to hepatic lipogenesis or AMP-activated protein kinase (AMPK) activation. Instead, PHG improved mitochondrial function by reducing oxidative stress, enhancing ATP production, and increasing anti-oxidant enzyme activity. PHG also relaxed gastric smooth muscles via potassium channel activation and nitric oxide (NO) signaling, potentially delaying gastric emptying. A pilot intervention in pre-diabetic men confirmed PHG’s efficacy in improving postprandial glycemic control and altering lipid metabolism. These findings suggest PHG as a potential therapeutic for NAFLD and insulin resistance, acting through mechanisms involving mitochondrial protection, anti-oxidant activity, and gastric motility modulation. Further clinical evaluation is warranted to explore PHG’s full therapeutic potential.

Estimating the postmortem interval (PMI) has remained the subject of investigations in forensic medicine for many years. Every kind of death results in changes in metabolites in body tissues and fluids due to lack of oxygen, altered circulation, enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites. Metabolic changes may provide markers determining the time since death, which is challenging in current analytical and observation-based methods. The study includes metabolomics analysis of blood with the use of an animal model to determine the biochemical changes following death. LC-MS is used to fingerprint postmortem porcine blood. Metabolites, significantly changing in blood after death, are selected and identified using univariate statistics. Fifty-one significant metabolites are found to help estimate the time since death in the early postmortem stage. Hypoxanthine, lactic acid, histidine, and lysophosphatidic acids are found as the most promising markers in estimating an early postmortem stage. Selected lysophosphatidylcholines are also found as significantly increased in blood with postmortal time, but their practical utility as PMI indicators can be limited due to a relatively low increasing rate. The findings demonstrate the great potential of LC-MS-based metabolomics in determining the PMI due to sudden death and provide an experimental basis for applying this attitude in investigating various mechanisms of death. As we assume, our study is also one of the first in which the porcine animal model is used to establish PMI metabolomics biomarkers.

The relationship of high-carbohydrate (HC) meal intake to metabolic syndrome is still not fully explained. Metabolomics has the potential to indicate metabolic pathways altered by HC meals, which may improve our knowledge regarding the mechanisms by which HC meals may contribute to metabolic syndrome development. The fasting and postprandial metabolic response to HC or normo-carbohydrate (NC) meals with/without cinnamon + capsicum intake was evaluated using untargeted metabolomics and compared between normal-weight (NW) and overweight/obese (OW/OB) healthy men. Healthy male participants (age-matched) were divided into two groups (12 subjects per group). One was composed of men with normal weight (NW) and the other of men with overweight/obesity (OW/OB). On separate visits (with 2–3 week intervals), the participants received standardized HC or NC meals (89% or 45% carbohydrates, respectively). Fasting (0 min) and postprandial (30, 60, 120, 180 min) blood were collected for untargeted plasma metabolomics. Based on each metabolic feature’s intensity change in time, the area under the curve (AUC) was calculated. Obtained AUCs were analyzed using multivariate statistics. Several metabolic pathways were found dysregulated after an HC meal in people from the OW/OB group but not the NW group. The consumption of HC meals by people with overweight/obesity led to a substantial increase in AUC, mainly for metabolites belonging to phospholipids and fatty acid amides. The opposite was observed for selected sphingolipids. The intake of cinnamon and capsicum normalized the concentration of selected altered metabolites induced by the intake of HC meals. A HC meal may induce an unfavourable postprandial metabolic response in individuals with overweight/obesity, and such persons should avoid HC meals.

The pathogenesis of the disorders of calcium metabolism is not fully understood. This review discusses the studies in which metabolomics was applied in this area. Indeed, metabolomics could play an essential role in discovering biomarkers and elucidating pathological mechanisms. Despite the limited bibliography, the present review highlights the potential of metabolomics in identifying the biomarkers of some of the most common endocrine disorders, such as primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), calcium deficiency, osteoporosis and vitamin D supplementation. Metabolites related to above-mentioned diseorders were grouped into specific classes and mapped into metabolic pathways. Furthermore, disturbed metabolic pathways can open up new directions for the in-depth exploration of the basic mechanisms of these diseases at the molecular level.

WSTĘP Nowotwór złośliwy kości rzadko wykrywany jest w jego wczesnym stadium i zazwyczaj w momencie diagnozy występuje już naciekanie tkanek miękkich. Objawy, które występują to ból, który nasila się w nocy, pogrubienie tkanek oraz ograniczenie ruchomości kończyny wynikające z destrukcji kości.CELEM PRACY był opis przypadku pacjenta po resekcji nowotworu złośliwego kości (Fibrolastic osteosarcoma) oraz stworzenie programu kompleksowej rehabilitacji pooperacyjnej. MATERIAŁ I METODY Analiza przypadku dokonana w niniejszej pracy potwierdza potrzebę holistycznego traktowania pacjenta ze zdiagnozowanym nowotworem złośliwym kości. U pacjent A.S. w wieku 23 lat rozpoznano torbiel tętniakowatą szyjki kości udowej lewej ze złamaniem patologicznym i rozległą destrukcją kości. Wykonano leczenie radykalne z całkowitą alloplastyką poresekcyjną. Opisano fizjoterapię szpitalną i rehabilitację 5 miesięcy po zabiegu operacyjnym. Praca potwierdza konieczność całościowego zastosowania procesu opieki nad pacjentem, który obejmuje diagnostykę, leczenie oraz rehabilitację.WYNIKI Fizjoterapia jest wprowadzana dobę po operacji i trwa do momentu wypisania pacjenta do domu. Metody i ćwiczenia fizjoterapeutyczne dostosowuje się do zakresu operacji, stanu ogólnego i wieku chorego. Celem jest uzyskanie przez pacjenta jak największej samodzielności poruszania się i wykonywania czynności dnia codziennego. W rehabilitacji poszpitalnej dąży się do przywrócenia prawidłowej, możliwej do osiągnięcia, ruchomości i stabilności stawów. Pacjent powinien przyjmować poprawny wzorzec chodu przy możliwie minimalnej asekuracji sprzętem ortopedycznym. WNIOSKI 1. Pacjenci po zabiegu resekcji części bliższej kości udowej i aloplastyce GMRS powinni rozpocząć rehabilitację już pierwszego dnia po zabiegu opeeracyjnym. 2. Terapia manualna i osteopatia są niezmiernie ważne w programie rehabilitacji po zabiegu operacyjnym usunięcia nowotworu kości.

Breast cancer is the most common cancer of women—it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.