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Hepatocyte produced matrix metalloproteinases are regulated by CD147 in liver fibrogenesis.

BACKGROUND: The classical paradigm of liver injury asserts that hepatic stellate cells (HSC) produce, remodel and turnover the abnormal extracellular matrix (ECM) of fibrosis via matrix metalloproteinases (MMPs). In extrahepatic tissues MMP production is regulated by a number of mechanisms including expression of the glycoprotein CD147. Previously, we have shown that CD147 is expressed on hepatocytes but not within the fibrotic septa in cirrhosis [1]. Therefore, we investigated if hepatocytes produce MMPs, regulated by CD147, which are capable of remodelling fibrotic ECM independent of the HSC

Chloride channels activated by hypotonicity in N2A neuroblastoma cell line.

By using the patch-clamp technique we have shown that, in hypotonic extracellular solutions, the mouse neuroblastoma cells Neuro2A (N2A) develop ionic currents mediated by a chloride-selective channel which is also permeable to other anions in accordance with the permeability sequence: I->Br->Cl->gluconate->glutamate-. The currents persist for several hours when Mg-ATP is present in the recording pipette but occur only transiently in the absence of Mg-ATP. Typical blockers of anions channels such as La3+ and Zn2+ do not affect the hypotonicity-activated channel; conversely, the stilbene sulfon

Bone-Seeking Matrix Metalloproteinase Inhibitors for the Treatment of Skeletal Malignancy.

Matrix metalloproteinases (MMPs) are a family of enzymes involved at different stages of cancer progression and metastasis. We previously identified a novel class of bisphosphonic inhibitors, selective for MMPs crucial for bone remodeling, such as MMP-2. Due to the increasing relevance of specific MMPs at various stages of tumor malignancy, we focused on improving potency towards certain isoforms. Here, we tackled MMP-9 because of its confirmed role in tumor invasion, metastasis, angiogenesis, and immuno-response, making it an ideal target for cancer therapy. Using a computational analysis, we

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… Compound 10 , bearing a bromine atom in 3’ position, showed a complete loss of activity on MMP-9 and, overall, an inferior activity profile towards all tested MMPs when compared to its isomer compound 9 . … Compound 9 , in particular, almost perfectly fits in the hydrophobic field calculated by SiteMap for MMP-9, with the bromine substituent interacting with the Arg249 ( Figure 5 and Figure S4 ). …

[Determination of polybrominated diphenyl ethers in marine sediments by composite chromatography column purification-gas chromatography-negative chemical ionization-mass spectrometry].

Polybrominated diphenyl ethers (PBDEs) are used as additive flame retardants. Because they lack the ability to form chemical bonds, PBDEs can easily enter the sediment environment. The accurate qualitative and quantitative analysis of PBDEs in sediments is of great importance for the accurate assessment of PBDE pollution in this environment. Sediments contain many impurities. Therefore, PBDEs in sediment should be purified before analysis to reduce the matrix effect. A method based on gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI/MS) was developed to determine 13 PB

Synthetic ion transporters that work with anion-π interactions, halogen bonds, and anion-macrodipole interactions.

The transport of ions and molecules across lipid bilayer membranes connects cells and cellular compartments with their environment. This bio … n bonds. Halogen bonds originate from the σ-hole that appears on top of electron-deficient iodines, bromines, and chlorines. Halogen-bond donors are ideal for anion transport because they are as strong and at least as directional as hydrogen-bond donors, but also hydrophobic. The discovery of the smallest possible organic anion transporter, trifluoroiodom …

Associations between in utero exposure to polybrominated diphenyl ethers, pathophysiological state of fetal growth and placental DNA methylation changes.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are environmental chemicals with harmful effects on pregnancy, but their effects on adverse developmental outcomes are not fully understood. The placental DNA methylation is strongly influenced by prenatal environmental factors and has been linked to fetal growth. OBJECTIVE: To evaluate the association between in utero PBDEs exposure, placental DNA methylation changes (growth regulatory genes), and pathophysiology of fetal growth (birth outcomes, fetal growth retardation) in a population-based pregnancy cohort study. METHODS: This was a nest

Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.

Marine-derived bisindoles exhibit structural diversity and exert anti-cancer influence through multiple mechanisms. Comprehensive research has shown that the development success rate of drugs derived from marine natural products is four times higher than that of other natural derivatives. Currently, there are 20 marine-derived drugs used in clinical practice, with 11 of them demonstrating anti-tumor effects. This article provides a thorough review of recent advancements in anti-tumor exploration involving 167 natural marine bisindole products and their derivatives. Not only has enzastaurin ent

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… The results indicated that the introduction of a hydroxyl group enhanced cytotoxicity, whereas the introduction of a bromine substituent reduced it [ 12 ]. … ChemInform Abstract: Brominated Bis(Indole) Alkaloids from the Marine Sponge Hexadella sp ChemInform 1990 21 10.1002/chin.199023305 46. Cruz P.G. Martínez Leal J.F. Daranas A.H. Pérez M. Cuevas C. …

Structure and ligand of a histone acetyltransferase bromodomain.

Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In

Phase III interlaboratory study of FETAX. Part 3. FETAX validation using 12 compounds with and without an exogenous metabolic activation system.

FETAX (Frog Embryo Teratogenesis Assay-Xenopus) is a 96-h whole-embryo developmental toxicity screening assay that can be used in ecotoxicology and in detecting mammalian developmental toxicants when an in vitro metabolic activation system is employed. A standardized American Society for Testing and Materials (ASTM) guide for the conduct of FETAX has been published, along with a companion atlas that helps in embryo staging and in identifying malformations. As part of the ASTM process, an interlaboratory validation study was undertaken to evaluate the repeatability and reliability of FETAX and

The therapeutic potential of colchicine in oncology studies: from structural modification and targeted delivery to clinical management.

Colchicine, a classical microtubule-targeting agent (MTA), exhibits remarkable anti-tumor potential, but its clinical translation is severely restricted by a narrow therapeutic window, systemic off-target toxicity, and complex pharmacokinetic vulnerabilities. Driven by the objective of "toxicity reduction and efficacy enhancement," this review comprehensively summarizes colchicine's multidimensional translational research. First, precise chemical modifications of its tricyclic scaffold and multi-site synergistic strategies are analyzed, exploring structure-activity relationship (SAR) mechanism

Role of metabolism in 1-bromopropane-induced hepatotoxicity in mice.

A possible role of metabolism in 1-bromopropane (1-BP)-induced hepatotoxicity was investigated in male ICR mice. The depletion of glutathione (GSH) by formation of GSH conjugates was associated with increased hepatotoxicity in 1-BP-treated mice. The formation of S-propyl and 2-hydroxypropyl GSH conjugates were identified in the liver following 1-BP treatment. In addition, the formation of reactive metabolites of 1-BP by certain cytochrome P-450 (CYP) may be involved in 1-BP-induced hepatotoxicity. The decreased content of hepatic GSH produced by 1-BP was associated not only with increased acti

Electrophysiology and immunohistochemistry in the hippocampal ca1 and the dentate gyrus of rats chronically exposed to 1-bromopropane, a substitute for specific chlorofluorocarbons.

1-Bromopropane is a newly introduced substitute for specific chlorofluorocarbons whose production was prohibited because of depletion of ozone layers. In this study, we analyzed disinhibitory effects induced by repetitive inhalation of 1-bromopropane for 12 weeks in the hippocampal CA1 and the dentate gyrus. In addition, reversal of the disinhibitory effects was examined 4 weeks after 1-bromopropane inhalation ceased. Exposure rats were placed in a stainless steel inhalation chamber at a concentration of 700 ppm, while the control group was provided only room air in the same type of chamber. P

[Screening of organophosphorus flame retardant residues in rice by QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry].

Organophosphorus flame retardants (OPFRs) have emerged as good alternatives to brominated flame retardants, the use of which is globally restricted. In this study, a screening method based on QuEChERS-gas chromatography-quadrupole time-of-flight mass spectrometry (GC-Q-TOF/MS) was established for the determination of 21 OPFRs in rice. First, full scan (scanning range, m/z 50-450) was performed with a mixed standard solution of the 21 OPFRs (0.1 μg/g) by GC-Q-TOF/MS. The fragmentation pathways of these OPFRs were then investigated to explore their cleavage fragments, the interrelationships amon

Changes in Renal Function and Oxidative Status Associated with the Hypotensive Effects of Oleanolic Acid and Related Synthetic Derivatives in Experimental Animals.

PURPOSE: The triterpene oleanolic acid (OA) is known to possess antihypertensive actions. In the present study we to compared the effects of the triterpene on mean arterial blood pressure (MAP) and kidney function following acute administration in normotensive animals with those of its related oleanane synthetic derivatives (brominated oleanolic acid, Br-OA and oleanolic acid methyl ester, Me-OA). We also used experimental models of hypertension to further explore the effects of sub-chronic oral OA treatment and evaluated influences on oxidative status. METHODS: OA was extracted from dried fl

Lactation exposure to BDE-153 damages learning and memory, disrupts spontaneous behavior and induces hippocampus neuron death in adult rats.

OBJECTIVE: To study the effects of 2,2',4,4',5,5'-hexa-brominated diphenyl ether (BDE-153) exposure during lactation on the learning and memory abilities, spontaneous behavior and brain cells of adult rats and to elicit basic information on PBDE's developmental neurotoxicity. METHODS: Newborn male rat pups were randomly categorized into the following groups (15 pups per group), according to their weights and litters: a control group, and 1mg/kg, 5mg/kg and 10mg/kg BDE-153 groups. At postnatal day 10 (PND10), the pups in the BDE-153 groups were intraperitoneally injected once with BDE-153 plan

Comparison of aerosol therapy with different perfluorocarbons in surfactant-depleted animals.

OBJECTIVE: The study investigates the effectiveness of aerosol treatment on gas exchange and pulmonary inflammatory reaction using perfluorocarbons with different molecular structure and vapor pressure. DESIGN: Experimental, prospective, randomized, controlled study. SETTING: Experimental laboratory at a university hospital. SUBJECTS: Twenty anesthetized neonatal piglets assigned to four groups. INTERVENTIONS: After establishment of lung injury by bronchoalveolar lavage, piglets either received aerosolized FC77 (n = 5), perfluorooctylbromide (n = 5), or FC43 (n = 5, 10 mL x kg(-1) x hr(-1)

Доказательства потенциала гуанидов против Leishmania (Viannia) braziliensis: исследование витро эффективности, токсичности и влияния на ответ иммунной системы.

Лейшманиаз — это сложная группа инфекционных и паразитарных заболеваний, которая поражает десятки тысяч людей на пяти континентах. Лечение лейшманиаза остается сложной задачей, так как оно зависит от лекарств, известных своей высокой токсичностью и ограниченной эффективностью, что делает необходимым поиск новых молекул, которые обеспечивали бы большую эффективность и безопасность. Настоящее исследование посвящено изучению влияния семи синтетических гуанидиновых производных (LQOF-G1, LQOF-G2, LQOF-G6, LQOF-G7, LQOF-G32, LQOF-G35 и LQOF-G36) на паразита Leishmania (Viannia) braziliensis и витроп

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… The synthesis of this new compound was due to the good results reported for LQOF-G2, a brominated guanidine. … Higher selectivity index values were observed for compounds containing specific chemical groups—nitro (LQOF-G1), tert -butyl (LQOF-G6), and bromine (LQOF-G2)—positioned in the ‘para’ position of the aniline moiety. …