Altered tyrosine metabolism

Navigating menopause involves traversing a complex terrain of hormonal changes that extend far beyond reproductive consequences. Menopausal transition is characterized by a decrease in estradiol-17β (E2), and the impact of menopause resonates not only in the reproductive system but also through the central nervous system, musculoskeletal, and gastrointestinal domains. As women undergo menopausal transition, they become more susceptible to frailty, amplifying the risk and severity of injuries, including traumatic brain injury (TBI)...

Residual cancer cells persist even after targeted therapies, serving as a reservoir for the subsequent acquisition of genetic alterations that lead to acquired drug resistance and tumor relapse. These initial drug-tolerant persisters (DTP) are phenotypically heterogenous with transient phenotypes attributed to epigenetic, metabolic, and cell-cycle changes. DTPs are responsible for the inevitable relapse seen in EGFR-mutant non-small cell lung cancer (NSCLC) despite high initial response to tyrosine kinase inhibitor (TKI) treatment...

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients...

This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 years of BW ± SD), weight (250.06 ± 25.18 kg), days in milk (39.11 ± 7.42 d), and averaged parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1...

Dietary absorption and digestion are influenced by the microbiota, morphology, and digestive enzymes of intestines, and fermentation is a popular and effective technique to enhance animal rearing growth performance. This study aims to explore the pivotal role of Muscovy duck probiotics fermented feedstuff (FF) in altering the growth performance by reshaping gut morphology, microorganisms and metabolism. The findings showed that FF considerably raised the levels of fatty acids (FA) and small peptides (7-19AA) in the diet...

Acral and mucosal melanomas are often driven by sequence variants in the KIT receptor tyrosine kinase, with nearly 40% harboring alterations in the KIT locus. Despite advances in the knowledge of KIT -mutated melanomas, little is known about the molecular reprogramming that occurs during KIT-mediated melanoma progression owing to the rarity of acral and mucosal melanomas and the lack of comprehensive biological tools and models. To this end, we used a murine model that allows us to ascertain the molecular underpinnings of the stages of cancer progression-transformation, tumorigenesis, immune engagement, and tumor escalation...

BACKGROUND: Obesity is a progressive metabolic disease that begins with lipid metabolism disorders. Aromatic amino acids (AAAs), including tryptophan, phenylalanine, and tyrosine, have diverse biological activities as nutrients. However, the underlying mechanisms by which AAAs affect lipid metabolism are unclear. OBJECTIVES: This study was designed to investigate the possible roles and underlying molecular mechanisms of AAA in the pathogenesis of lipid metabolism disorders...

BACKGROUND: Protein tyrosine phosphatase non-receptor type 7 (PTPN7) is a signaling molecule that regulates a multitude of cellular processes, spanning cell proliferation, cellular differentiation, the mitotic cycle, and oncogenic metamorphosis. However, the characteristic of PTPN7 in the glioma microenvironment has yet to be elucidated. METHODS: The prognostic value, genomic features, immune characteristics, chemotherapy prediction, and immunotherapy prediction of PTPN7 were systematically explored at the bulk sequencing level...

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis ...

A cell committed to proliferation must reshape its metabolism to enable robust yet balanced production of building blocks for the assembly of proteins, lipids, nucleic acids, and other macromolecules, from which two functional daughter cells can be produced. The metabolic remodeling associated with proliferation is orchestrated by a number of pro-proliferative signaling nodes, which include phosphatidylinositol-3 kinase (PI3K), the RAS family of small GTPases, and transcription factor c-myc In metazoan cells, these signals are activated in a paracrine manner via growth factor-mediated activation of receptor (or receptor-associated) tyrosine kinases...

INTRODUCTION: Osteoarthritis (OA) is a progressive disease that poses a significant threat to human health, particularly in aging individuals: Although sympathetic activation has been implicated in bone metabolism, its role in the development of OA related to aging remains poorly understood. Therefore, this study aimed to investigate how sympathetic regulation impacts aging-related OA through experiments conducted both in vivo and in vitro. METHODS: To analyze the effect of sympathetic regulation on aging-related OA, we conducted experiments using various mouse models...

Silica nanoparticles (SiNPs) could induce adverse pulmonary effects, but the mechanism was not clear enough. Metabolomics is a sensitive and high-throughput approach that could investigate the intrinsic causes of adverse health effects caused by SiNPs. The current investigation represented the first in vivo metabolomics study examining the chronic pulmonary toxicity of SiNPs at a low dosage, mimicking real human exposure situation. The recovery process after the cessation of exposure was also taken into consideration...

INTRODUCTION: Smoking is a public health threat due to its well described link to increased oxidative stress-related diseases including peripheral vascular disease and coronary artery disease. Tobacco use has been linked to risk of inpatient trauma morbidity including acute respiratory distress syndrome, however its mechanistic effect on comprehensive metabolic heterogeneity has yet to be examined. METHODS: Plasma was obtained on arrival from injured patients at a Level 1 Trauma Center and analyzed with modern mass spectrometry-based metabolomics...

The present study investigated the inhibitory and neuroprotective effects of Rubia yunnanensis alcohol extract (RY-A) on oxidative stress induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 cells. In vitro cultured HT22 cells were randomly divided into control, OGD/R, OGD/R + 100 µmol/l edaravone and OGD/R + 10, 20 and 40 µg/ml RY-A groups. Oxygen-sugar deprivation was performed with 10 mmol/l sodium dithionite combined with sugar-free DMEM medium for 2 h, followed by re-glycolization and reoxygenation for 2 h to establish an in vitro OGD/R model...

Malaria is the leading parasitic disease worldwide, with P. vivax being a major challenge for its control. Several studies have indicated metabolomics as a promising tool for combating the disease. The study evaluated plasma metabolomic profiles of patients with recurrent and non-recurrent P. vivax malaria in the Brazilian Amazon. Metabolites extracted from the plasma of P. vivax-infected patients were subjected to LC-MS analysis. Untargeted metabolomics was applied to investigate the metabolic profile of the plasma in the two groups...

Low temperatures limit the denitrification wastewater in activated sludge systems, but this can be mitigated by addition of redox mediators (RMs). Here, the effects of chlorophyll (Chl), 1,2-naphthoquinone-4-sulfonic acid (NQS), humic acid (HA), and riboflavin (RF), each tested at three concentrations, were compared for denitrification performance at low temperature, by monitoring the produced extracellular polymeric substances (EPS), and characterizing microbial communities and their metabolic potential. Chl increased the denitrification rate most, namely 4...

Psoriasis is a common chronic inflammatory skin disease with a complex pathogenesis involving immune system dysregulation and inflammation. Previous studies have indicated that metabolic abnormalities are closely related to the development and occurrence of psoriasis. However, the specific involvement of amino acid metabolism in the pathogenesis of psoriasis remains unclear. In this study, we conducted a comprehensive analysis of amino acid metabolism pathway changes in psoriasis patients using transcriptome data, genome-wide association studies (GWASs) data, and single-cell data...

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are classified as major mental disorders and together account for the second-highest global disease burden, and half of these patients experience symptom onset in adolescence. Several studies have reported both similar and unique features regarding the risk factors and clinical symptoms of these three disorders. However, it is still unclear whether these disorders have similar or unique metabolic characteristics in adolescents. We conducted a metabolomics analysis of plasma samples from adolescent healthy controls (HCs) and patients with MDD, BD, and SCZ...

Currently, the coronavirus disease 2019 (COVID-19) is becoming a serious threat to human health worldwide. Therefore, there is a great need to develop effective drugs against viral pneumonia. Diammonium glycyrrhizinate (DG), derived from Glycyrrhiza glabra L., has been demonstrated with significant anti-inflammatory properties. However, the therapeutic effects and mechanisms of DG on pneumonia require further clarification. In this study, mice received intratracheal injection of polyinosinic-polycytidylic acid (poly(I:C)) to induce pneumonia and were treated with DG...

Introduction: Drug dosages and combinations are the main factors that affect the efficacy of pleiotropic traditional Chinese medicine (TCM). Coptis chinensis Franch. (CF) is a representative TCM with multiple effects and is often combined with Tetradium ruticarpum (A. Jussieu) T. G. Hartley (TR) to treat cholestasis. The present study assessed the influence of CF dose and its combination with TR on the efficacy of CF in cholestasis treatment, including their effects on fecal metabolism and fecal microorganisms...