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Dual mechanisms for the fibrate-mediated repression of proprotein convertase subtilisin/kexin type 9.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with familial autosomal dominant hypercholesterolemia and is a natural inhibitor of the LDL receptor (LDLr). PCSK9 is degraded by other proprotein convertases: PC5/6A and furin. Both PCSK9 and the LDLr are up-regulated by the hypocholesterolemic statins. Thus, inhibitors or repressors of PCSK9 should amplify their beneficial effects. In the present study, we showed that PPARalpha activation counteracts PCSK9 induction by statins by repressing PCSK9 promoter activity and by increasing PC5/6A and furin expression. Quantification

Issues of normal tissue toxicity in patient and animal studies--effect of carbogen breathing in rats after 5-fluorouracil treatment.

Non-invasive magnetic resonance spectroscopy (MRS) can be used in the clinic to monitor the pharmacokinetics of the chemotherapeutic drug 5-fluorouracil (5-FU) and the effects of modifiers. We report two studies of 5-FU toxicity in normal tissue--one with patients and the other an animal study. 1) 19F MRS signals from fluoronucleotides, cytotoxic anabolites of 5-FU metabolism, were observed in the livers of two patients treated with 5-FU for colorectal cancer, shown by computed tomography (CT) and ultrasound (US) to have no liver metastases. This is the first report of non-invasive monitoring

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of b

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… Fluorine A daily intake of fluorine around 3–4 mg is mostly satisfied by tea and coffee, seafood, and fortified water, as well as dairy products [ 273 ]. … On top of this, nowadays, fluorine commonly takes part in the development of drugs for many different diseases, and its contribution to medicinal chemistry seems to be important as new fluorine-containing compounds are explored. …

Advancements in Targeted Radiopharmaceuticals: Innovations in Diagnosis and Therapy for Enhanced Cancer Management.

Radiopharmaceuticals (RPhs) represent a breakthrough in nuclear medicine due to their ability to provide precise diagnosis and targeted therapy for cancer by incorporating radioactive isotopes into carrier molecules. This review systematically discusses the recent advances in the development of RPhs, focusing on state-of-the-art probe design strategies and click chemistry applications that accelerate RPh syntheses and improve targeting efficiency. The manuscript synthesizes literature from multiple databases spanning January 2014 to April 2025, encompassing diagnostic modalities including posi

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… Recent advancements in this field include the use of novel radionuclides such as gallium‐68 [ 51 ] and fluorine‐18 [ 52 ] and the development of theranostic RPhs for simultaneous diagnosis and therapy. … Gray circles are for natural amino acids; blue circles represent unnatural amino acids; red highlights are for fluorine‐18 labeling; and purple highlights are for chelators for metal radionuclide labeling. Adapted from [ 78 ] 2025, Springer. …

Sialyltransferase Inhibitors for the Treatment of Cancer Metastasis: Current Challenges and Future Perspectives.

Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell meta

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… This mechanistic proposal suggests that incorporation of fluorine on the pyranose ring of sialic acid would give fluorinated CMP-sialic acids that may be weak ST substrates but perhaps good ST inhibitors [ 137 , 138 ]. … Table 7 Inhibition of α2,3-linked sialic acid in B16F10 cells by C-5-modified fluorinated sialic acid inhibitors 60 –67 (Data from [ 149 ]). …

Metal fume fever and polymer fume fever.

INTRODUCTION: Inhalational exposure to metal-containing fumes generated by welding and related processes may result in the development of the clinical syndrome known as "metal fume fever." Polymer fume fever is a separate and distinct but related disorder that has been associated with inhalational exposure to specific fluorinated polymer products, such as polytetrafluoroethylene or Teflon(®). We undertook a review of the peer-reviewed medical literature as it relates to these two disease entities in order to describe their epidemiology, pathophysiology, clinical presentation, diagnosis, treatm

¹⁸F-FDG PET/CT: a review of diagnostic and prognostic features in multiple myeloma and related disorders.

Conventional radiographic skeletal survey has been for many years the gold standard to detect the occurrence of osteolytic lesions in patients with multiple myeloma (MM). However, the introduction of more sensitive imaging procedures has resulted in an updated anatomic and functional Durie and Salmon "plus" staging system and has remarkably changed the diagnostic and prognostic approach to this tumor. It is now established that (18)fluorine-fluorodeoxyglucose ((18)F-FDG) positron-emission tomography (PET) combined with low-dose computed tomography (CT), shortly designated PET/CT, exhibits a hi…

(18)F-FDG positron emission tomography/computed tomography and (99m)Tc-MDP skeletal scintigraphy in a case of Erdheim-Chester disease.

Erdheim-Chester disease (ECD), first described by Jakob Erdheim and William Chester in 1930, is a rare form of non-Langerhan's cell histiocy … the diagnosis of sarcoidosis. Two weeks later, whole-body (from head to pelvis) plus lower limbs 18-fluorine-labelled 2-deoxy-2-fluoro-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) was performed. Uptake of (18)F-FDG was observed in the upper portion of the midbrain area (SUV(max) 7.1) and the pituitary gland (SUV(max) 7.3), …

Transformation of Follicular Lymphoma to a High-Grade B-Cell Lymphoma With MYC and BCL2 Translocations and Overlapping Features of Burkitt Lymphoma and Acute Lymphoblastic Leukemia: A Case Report and Literature Review.

Most commonly, histologic transformation (HT) from follicular lymphoma (FL) manifests as a diffuse large B-cell lymphoma, not otherwise spec … ad crampy abdominal pain in the absence of B symptoms. Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with CT (18F-FDG PET/CT) scan showed widespread adenopathy, diffuse splenic involvement, and substantial marrow involvement. Biopsy of a 2.4-cm right axillary node (SUVmax of 16.1) showed involvement by grade 3A FL wi …

Is (18)F-FDG PET really a promising marker for clinically relevant atherosclerosis?

Bural et al (2013), retrospectively investigated 143 subjects who received whole body fluorine-18-fluorodeoxyglucose- positron emission tomography ((18)F-FDG-PET) imaging for the assessment of non-cardiovascular diseases. They reported an increase of (18)F-FDG-positive lesions in various aortic segments, which increased with age, and were more pronounced in subjects being aged below 50 years as compared to those above 50. Bural et al also found the highest segmental (18)F-FDG-uptake in the descending thoracic aorta, but not in the abdominal aorta, where the majority of the most severe atherosc…

Биарил Фосфаты и фосфонаты как выборочные ингибаторы фактора транскрипции СТАТ4.

Коэффициент транскрипции STAT4 был связан с патогенезом аутоиммунных заболеваний, включая провокационное заболевание кишечника, множественный склероз, ревматоидный артрит и сахарный диабет. Здесь мы представляем P-biaryl фосфаты и фосфонаты в качестве первых малых ингибиторов СТАТ4. Наиболее мощный фосфат P-biaryl интенсифицировал домен взаимодействия белка и протеина STAT4, домен SH2, с субмикромолической пользой (Ki = 0,35 мкМ) и 14-кратной избирательностью по близкому члену семьи STAT3, который имеет тот же основной пептид, что и STAT4. Дальнейшая разработка привела к созданию ингибитора, у

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… Structural variations of the lower ring of 1 showed that a fluorine substituent in the 2‐position ( 6h , K i  = 0.56 ± 0.08 µM, Tables  1 and S1 ) improved both the activity and selectivity as compared to 1 (Tables  1 , S1 and S2 ). … In contrast, a fluorine substituent in the 3‐position ( 6i , K i  = 3.8 ± 0.1 µM) decreased the activity, as did the placement of two fluorine atoms in both the 2‐ and the 5‐position ( 6j , K i  = 2.0 ± 0.1 µM, Tables  1 and S1 ). …

Oxysterol-induced soluble endoglin release and its involvement in hypertension.

BACKGROUND: Ischemia in the placenta is considered the base of the pathogenesis of preeclampsia, a pregnancy-specific syndrome in which soluble endoglin (sEng) is a prognostic marker and plays a pathogenic role. Here, we investigated the effects of hypoxia and the downstream pathways in the release of sEng. METHODS AND RESULTS: Under hypoxic conditions, the trophoblast-like cell line JAR showed an increase in sEng parallel to an elevated formation of reactive oxygen species. Because reactive oxygen species are related to the formation of oxysterols, we assessed the effect of 22-(R)-hydroxycho

Metabotropic glutamate receptor 5 antagonist protects dopaminergic and noradrenergic neurons from degeneration in MPTP-treated monkeys.

Degeneration of the dopaminergic nigrostriatal system and of noradrenergic neurons in the locus coeruleus are important pathological features of Parkinson's disease. There is an urgent need to develop therapies that slow down the progression of neurodegeneration in Parkinson's disease. In the present study, we tested whether the highly specific metabotropic glutamate receptor 5 antagonist, 3-[(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, reduces dopaminergic and noradrenergic neuronal loss in monkeys rendered parkinsonian by chronic treatment with low doses of 1-methyl-4-phenyl-1,2,3,6-tetrah

Liver X receptors inhibit macrophage proliferation through downregulation of cyclins D1 and B1 and cyclin-dependent kinases 2 and 4.

Macrophages serve essential functions as regulators of immunity and homeostasis, and their proliferation contributes to pathogenesis of certain disorders. In this report, we show that induction of macrophage proliferation by the growth factor M-CSF is negatively modulated by agonists that activate the nuclear receptor liver X receptor (LXR), both in vitro and in vivo. Both isoforms LXR α and β are involved in the antiproliferative actions of LXR ligands in macrophages. In contrast, M-CSF does not exert negative effects on LXR-mediated gene expression. Treatment with LXR agonists results in the

Fabrication of bioactive composite scaffolds by electrospinning for bone regeneration.

Electrospun scaffolds are widely used for various biomedical applications. In this study, we prepared electrospun bioactive composite scaffolds combining hydroxyapatite, collagen (Col) and a synthetic polymer-PolyActive™-to mimic naturally occurring extracellular matrix for in situ bone regeneration. Human mesenchymal stem cells (hMSCs) adhered and proliferated on these scaffolds. Cells on all scaffold types showed an increased metabolic activity with time. On day 4, the metabolic activity of cells cultured on PolyActive™ (PA)-hydroxyapatite (HA)-Col in 1,1,1,3,3,3-hexafluoro-2-propanolhexaflu

Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats.

BACKGROUND & AIMS: Capillarization, characterized by loss of differentiation of liver sinusoidal endothelial cells (LSECs), precedes the onset of hepatic fibrosis. We investigated whether restoration of LSEC differentiation would normalize crosstalk with activated hepatic stellate cells (HSC) and thereby promote quiescence of HSC and regression of fibrosis. METHODS: Rat LSECs were cultured with inhibitors and/or agonists and examined by scanning electron microscopy for fenestrae in sieve plates. Cirrhosis was induced in rats using thioacetamide, followed by administration of BAY 60-2770, an a

Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRalpha.

HBV (hepatitis B virus) is a primary cause of chronic liver disease, which frequently results in hepatitis, cirrhosis and ultimately HCC (hepatocellular carcinoma). Recently, we showed that HBx (HBV protein X) expression induces lipid accumulation in hepatic cells mediated by the induction of SREBP1 (sterol-regulatory-element-binding protein 1), a key regulator of lipogenic genes in the liver. However, the molecular mechanisms by which HBx increases SREBP1 expression and transactivation remain to be clearly elucidated. In the present study, we demonstrated that HBx interacts with LXRalpha (liv

YbiV from Escherichia coli K12 is a HAD phosphatase.

The protein YbiV from Escherichia coli K12 MG1655 is a hypothetical protein with sequence homology to the haloacid dehalogenase (HAD) superfamily of proteins. Although numerous members of this family have been identified, the functions of few are known. Using the crystal structure, sequence analysis, and biochemical assays, we have characterized YbiV as a HAD phosphatase. The crystal structure of YbiV reveals a two-domain protein, one with the characteristic HAD hydrolase fold, the other an inserted alpha/beta fold. In an effort to understand the mechanism, we also solved and report the struct

Extraskeletal multiple myeloma presenting with an atrial mass: a case report and a review of the literature.

INTRODUCTION: Extraskeletal presentation at diagnosis or during the course of multiple myeloma is a rare event. The prognosis is usually very poor. At the moment there is no agreed gold standard for the treatment of this presentation. CASE PRESENTATION: A 79-year-old Caucasian woman was treated at our hospital for right atrial myeloma localization. Our patient showed the following signs and symptoms of congestive heart failure: dyspnea, hypotension, cyanosis and facial edema. Surgery was not considered feasible due to the extent of the disease. Our patient underwent external-beam radiation th

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… Computed tomography (CT) of her chest documented the presence of a right atrial mass (42mm × 53mm), confirmed by subsequent magnetic resonance imaging (MRI) and fluorine-18-fluorodeoxyglucose positron emission tomography (F18-FDG PET). … Figure 1 Radiographic images of the mass. ( A ) Computed tomography of the chest documenting the atrial mass; ( B ) fluorine-18-fluorodeoxyglucose positron emission tomography confirming this data. Restaging examinations documented stable bone disease. …

Prostate-specific membrane antigen (PSMA)-ligand positron emission tomography and radioligand therapy (RLT) of prostate cancer.

From a clinical perspective, prostate-specific membrane antigen (PSMA) is a valuable target for both diagnosis and radioligand therapy (RLT) of prostate cancer. The term 'specific' has been used to characterize a histologic hallmark of overexpression in the membrane of most prostate cancer. Many PSMA ligands have been developed since the previous decade and have been used in several clinical trials and clinical studies. However, procedure, specification, protocol, interpretation criteria, radiation dose, and cost-effectiveness of PSMA ligands have not been fully explained. Regardless of worldw