Biomolecules

BACKGROUND: We investigated the relationship of matrix metalloproteinases (MMPs), cardio-ankle vascular index (CAVI), and Gray-Scale Median (GSM) score with the severity and vulnerability of carotid atherosclerosis and major adverse cardiovascular events (MACE) during follow-up of carotid artery revascularization. METHODS: We enrolled 262 patients undergoing carotid revascularization therapy (GRT), 109 asymptomatic patients with low-grade carotid stenosis (40-70%) receiving conservative treatment (GCT), and 92 age- and sex-matched control subjects without carotid atherosclerosis (GCO)...

Age-related loss of vestibular function and hearing are common disorders that arise from the loss of function of the inner ear and significantly decrease quality of life. The underlying pathophysiological mechanisms are poorly understood and difficult to investigate in humans. Therefore, our study examined young (1.5-month-old) and old (24-month-old) C57BL/6 mice, utilizing physiological, histological, and transcriptomic methods. Vestibular sensory-evoked potentials revealed that older mice had reduced wave I amplitudes and delayed wave I latencies, indicating reduced vestibular function...

The increase in presynaptic striatal dopamine is the main dopaminergic abnormality in schizophrenia (SCZ). SCZ is primarily treated by modulating the activity of monoamine systems, with a focus on dopamine and serotonin receptors. Glial cell line-derived neurotrophic factor (GDNF) is a strong dopaminergic factor, that recently was shown to correlate with SCZ in human CSF and in striatal tissue. A 2-3-fold increase in GDNF in the brain was sufficient to induce SCZ-like dopaminergic and behavioural changes in mice...

Lysophosphatidic acid (LPA) is a promising biomarker candidate to screen for ovarian cancer (OC) and potentially stratify and treat patients according to disease stage. LPA is known to target the actin-binding protein gelsolin which is a key regulator of actin filament assembly. Previous studies have shown that the phosphate headgroup of LPA alone is inadequate to bind to the short chain of amino acids in gelsolin known as the PIP2 -binding domain. Thus, the molecular-level detail of the mechanism of LPA binding is poorly understood...

Brain-derived neurotrophic factor (BDNF) is implicated in the etiology and treatment response in major depressive disorder (MDD). However, peripheral BDNF concentrations have not been compared across different MDD stages. Bright light therapy (BLT) offers some potential in treatment-resistant depression (TRD), but its effects on BDNF levels are unknown. This study included a cross-sectional analysis of plasma BDNF concentration in females with TRD, unmedicated MDD patients, and healthy controls (HC), and measurements of longitudinal BLT effects on plasma BDNF levels in TRD patients...

Our study aimed to conduct a comprehensive biochemical profiling and metabolomics analysis to investigate the effects of arsenic-induced metabolic disorders, with a specific focus on disruptions in lipid metabolism, amino acid metabolism, and carbohydrate metabolism. Additionally, we sought to assess the therapeutic potential of resveratrol (RSV) as a remedy for arsenic-induced diabetes, using metformin (MF) as a standard drug for comparison. We measured the total arsenic content in mouse serum by employing inductively coupled plasma mass spectrometry (ICP-MS) after administering a 50-ppm solution of sodium arsenate (50 mg/L) in purified water...

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) have transformed the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer over the last decade. These inhibitors are currently established as first- and second-line systemic treatment choices for both endocrine-sensitive and -resistant breast cancer populations alongside endocrine therapy (ET) or monotherapy. Data on targeted therapy continue to mature, and the number of publications has been constantly rising...

The yeast Hyphopichia wangnamkhiaoensis excretes a brilliant yellow fluorescent compound into its growth culture. In this study, we isolated and identified this compound using reverse-phase high-performance liquid chromatography-diode array detector (RP-HPLC-DAD) as well as 1 H NMR and UV-Vis spectroscopy. Two of the three RP-HPLC-DAD methods used successfully separated the fluorescent compound and involved (1) a double separation step with isocratic flow elution, first on a C18 column and later on a cyano column, and (2) a separation with a linear gradient elution on a phenyl column...

The SARS-CoV-2 virus rapidly spread worldwide, threatening public health. Since it emerged, the scientific community has been engaged in the development of effective therapeutics and vaccines. The subunit S1 in the spike protein of SARS-CoV-2 mediates the viral entry into the host and is therefore one of the major research targets. The S1 protein is extensively glycosylated, and there is compelling evidence that glycans protect the virus' active site from the human defense system. Therefore, investigation of the S1 protein glycome alterations in the different virus variants will provide a view of the glycan evolution and its relationship with the virus pathogenesis...

The glutathione transferase A3-3 (GST A3-3) homodimeric enzyme is the most efficient enzyme that catalyzes isomerization of the precursors of testosterone, estradiol, and progesterone in the gonads of humans and horses. However, the presence of GST A3-3 orthologs with equally high ketosteroid isomerase activity has not been verified in other mammalian species, even though pig and cattle homologs have been cloned and studied. Identifying GSTA3 genes is a challenge because of multiple GSTA gene duplications (e...

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2 O2 , remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2)...

Circulating tumor DNA (ctDNA) has been suggested as a surrogate biomarker for early detection of cancer recurrence. We aimed to explore the utility of ctDNA as a noninvasive prognostic biomarker in newly diagnosed head and neck squamous cell carcinoma (HNSCC) patients. Seventy HNSCC specimens were analysed for the detection of TP53 genetic alterations utilizing next-generation sequencing (NGS). TP53 mutations were revealed in 55 (79%). Upon detection of a significant TP53 mutation, circulating cell-free DNA was scrutinized for the presence of the tumor-specific mutation...

Eosinophilic gastrointestinal disease (EGID) is divided into eosinophilic esophagitis (EoE) and non-eosinophilic esophagitis eosinophilic gastrointestinal disease (non-EoE-EGID) based on the involved gastrointestinal segments. Reports regarding non-EoE-EGID are limited, in part because of its rarity. The present study was performed to review non-EoE-EGID, including its pathogenesis, diagnosis, treatment, and prognosis. Additionally, details regarding 28 cases of non-EoE-EGID recently diagnosed at our Japanese tertial medical center are presented and compared with 20 EoE cases diagnosed during the same period at the same medical center...

Posttraumatic osteoarthritis (PTOA) arises secondary to joint injuries and is characteristically driven by inflammatory mediators. PTOA is often studied in the setting of ACL tears. However, a wide range of other injuries also lead to PTOA pathogenesis. The purpose of this study was to characterize the morphological changes in the uninjured ACL in a PTOA inflammatory environment. We retrospectively reviewed 14 ACLs from 13 Yucatan minipigs, 7 of which had undergone our modified intra-articular drilling (mIAD) procedure, which induced PTOA through inflammatory mediators...

The high structural similarity, especially in transmembrane regions, of dopamine, norepinephrine, and serotonin transporters, as well as the lack of all crystal structures of human isoforms, make the specific targeting of individual transporters rather challenging. Ligand design itself is also rather limited, as many chemists, fully aware of the synthetic and analytical challenges, tend to modify lead compounds in a way that reduces the number of chiral centers and hence limits the potential chemical space of synthetic ligands...

BACKGROUND: Pompe disease is a lysosomal storage disease characterised by skeletal and respiratory muscle weakness. Since 2006, enzyme replacement therapy (ERT) with alglucosidase alfa has been available. ERT significantly improves the prognosis of patients with Pompe disease. The effect of high antibody titres on treatment response in adults with late-onset Pompe disease (LOPD) remains unclear but may contribute to interpatient variation. We therefore conducted a systematic review on this subject...

Plant extracellular vesicles (P-EVs) are considered promising functional food ingredients due to their various health benefits. In this study, blueberry extracellular vesicles (B-EVs) were collected and purified by size exclusion chromatography (SEC). The chemical compounds in B-EV extracts were analyzed by LC-MS/MS. In addition, the stability of B-EVs was evaluated during short- and long-term storage, heating, and in vitro digestion. The results showed that the B-EVs had a desirable particle size (88.2 ± 7...

Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid mediators is reported in the disease with a predominance of the inflammatory cascade derived from n-6 polyunsaturated fatty acids (n-6 PUFAs). Bioactive lipid mediators derived from arachidonic acid (AA) are involved in the inflammatory functions of T cells in psoriasis, whereas n-3 PUFAs' derivatives are anti-inflammatory metabolites. Here, we sought to evaluate the influence of a supplementation of the culture media with eicosapentaenoic acid (EPA) on the lipid profile of a psoriatic skin model produced with polarized T cells...

BACKGROUND: Cocaine use disorder (CUD) is a relapsing brain disease caused by a chronic drug intake that involves neural mechanisms and psychological processes, including depression. Preclinical and clinical studies have demonstrated the promise of pharmacological drugs in controlling the reinstatement of cocaine by targeting the N-methyl-D-aspartate (NMDA) receptor. Recent evidence has revealed that esketamine, a (S) enantiomer of ketamine, shows a high affinity to NMDA receptors and has been used in clinical trials to treat moderate-to-severe depression...

Estrogen is indispensable in health and disease and mainly functions through its receptors. The protection of the cardiovascular system by estrogen and its receptors has been recognized for decades. Numerous studies with a focus on estrogen and its receptor system have been conducted to elucidate the underlying mechanism. Although nuclear estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to be classical receptors that mediate genomic effects, studies now show that GPER mainly mediates rapid signaling events as well as transcriptional regulation via binding to estrogen as a membrane receptor...