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PubMed Journal Database | Chemico-biological interactions RSS

09:36 EDT 27th May 2019 | BioPortfolio

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Showing PubMed Articles 1–25 of 469 from Chemico-biological interactions

Molecular modelling studies on the interactions of 7-methoxytacrine-4-pyridinealdoxime with VX-inhibited human acetylcholinesterase. A near attack approach to assess different spacer-lengths.

The novel prophylactic agent 7-methoxytacrine-4-pyridinealdoxime is a hybrid compound that was formerly designed to keep acetylcholinesterase resistant to organophosphates inhibitors and to reactivate that enzyme in the case of intoxication by such inhibitors. In rational design, a 5-carbon length-spacer hybrid compound was synthesized to evaluate its inhibitory and reactivation capabilities. In this work, theoretical results were achieved through molecular modelling techniques, taking for granted enzymatic...

Matrine induces apoptosis and autophagy of glioma cell line U251 by regulation of circRNA-104075/BCL-9.

Matrine, a traditional Chinese medicine, has been reported to exert anti-tumor effects in several types of cancers. Here, we explored the anti-tumor effects of matrine on the glioma cells.

EPA adopts LNT: New historical perspectives.

This paper provides an historical assessment of how the linear non-threshold (LNT) model became adopted as policy by the United States Environmental Protection Agency (US EPA) in 1975 [1] and how prior United States National Academy of Sciences (US NAS) radiation advisory panels may have affected this EPA decision. The paper highlights a generally unrecognized set of recommendations of the 1960 Biological Effect of Atomic Radiation [2] Genetics and Medical/Pathology Panels that did not support LNT for cance...

Methylglyoxal activates osteoclasts through JNK pathway leading to osteoporosis.

Diabetes mellitus is characterized by chronic hyperglycemia and its diverse complications. Hyperglycemia is associated with inflammatory responses in different organs, and diabetic patients have a higher risk of bone fracture due to increased bone weakness. Methylglyoxal, a reactive advanced glycation end product precursor, is known to have increased level in diabetic patients. The accumulation of methylglyoxal promotes inflammation and it may play a role in diabetes related osteoporosis. In this study, the...

Wogonin pre-treatment attenuates cisplatin-induced nephrotoxicity in rats: Impact on PPAR-γ, inflammation, apoptosis and Wnt/β-catenin pathway.

Cisplatin, a platinum chemotherapeutic agent, is used in a diversity of malignancies; nevertheless, the excessive nephrotoxicity following cisplatin treatment is the dose-limiting devastating reaction. This study was designed to explore the possible nephroprotective impact of wogonin, a forceful anti-oxidant, anti-inflammatory, and anti-tumor agent, in a rat model of cisplatin-induced renal injury. The potential nephroprotective mechanisms were additionally investigated. Wogonin was given at a dose of 40 ...

In vitro and in vivo studies of the metabolic activation of chelidonine.

Chelidonium majus L. is an herbal medicine widely employed in Europe and Western Asia. Chelidonine (CHE) is a major constituent of the herb and has been reported to be an inhibitor of the cytochrome P450 enzymes (CYP). The major objective of the present study was to study the metabolic pathways of CHE in order to identify potential reactive metabolites responsible for the enzyme inhibition. Three oxidative metabolites (M1-M3) were detected in human liver microsomal incubations after exposure to CHE. M1 and ...

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on acetylcholinesterase during myogenic differentiation of contractile rat primary skeletal muscle cells.

Emerging data indicate that prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could interfere with myogenic differentiation in vivo. Acetylcholinesterase (EC3.1.1.7; AChE), an enzyme critical for cholinergic neurotransmission, is abundantly expressed in neurons and mature myotubes, and we recently found that muscle AChE expression was suppressed in parallel with the inhibition of myogenic differentiation upon TCDD treatment in mouse C2C12 cells. This TCDD-induced suppression of muscle AChE w...

Protective effect of morin on doxorubicin-induced hepatorenal toxicity in rats.

Although Doxorubicin (DOX) is a widespread drug used in the treatment of cancer, its clinical use is restricted due to its common side effects. In addition, administrating DOX with an antioxidant has recently become a new strategy in preventing the side effects of DOX. The protective effects of morin, a natural flavonoid, against DOX-induced liver and kidney damage in rats were investigated biochemically, immunohistochemically and histopathologically in this study. The experimental procedure was planned as ...

The evolution of phosphotriesterase for decontamination and detoxification of organophosphorus chemical warfare agents.

The organophosphorus chemical warfare agents were initially synthesized in the 1930's and are some of the most toxic compounds ever discovered. The standard means of decontamination are either harsh chemical hydrolysis or high temperature incineration. Given the continued use of chemical warfare agents there are ongoing efforts to develop gentle environmentally friendly means of decontamination and medical counter measures to chemical warfare agent intoxication. Enzymatic decontamination offers the benefits...

Surface screening, molecular modeling and in vitro studies on the interactions of aflatoxin M1 and human enzymes acetyl- and butyrylcholinesterase.

Aflatoxin M1 (AFM1) is a mycotoxin produced by Aspergillus fungi and found in contaminated milk, breastfeed and dairy products, being highly toxic and carcinogenic to humans and other mammalian species. It is also produced in the human body as a metabolite of aflatoxin B1 (AFB1), one of the most toxic natural products known. Previous studies have shown that AFM1 is a potential inhibitor of the enzyme acetylcholinesterase (AChE), and therefore, a potential neurotoxic agent. In this work, surface screening (S...

Activation of PINK1-Parkin-dependent mitophagy in Tri-ortho-cresyl phosphate-treated Neuro2a cells.

Tri-ortho-cresyl phosphate (TOCP) is a typical organophosphorus compound that can cause organophosphate-induced delayed neuropathy (OPIDN), which is pathologically characterized by axonal degeneration. Nowadays, mitochondrial dysfunction is regarded as a potential mechanism contributing to OPIDN progress. Mitophagy, a selective type of autophagy, is required to segregate damaged mitochondria from healthy mitochondrial networks and deliver them to lysosome for degradation. This research was designed to inves...

Assessment of ionizable, zwitterionic oximes as reactivating antidotal agents for organophosphate exposure.

Since the development in the 1950's of 2-PAM (Pralidoxime), an antidote that reactivates organophosphate conjugated acetylcholinesterase in target tissues upon pesticide or nerve agent exposure, improvements in antidotal therapy have largely involved congeneric pyridinium aldoximes. Despite seminal advances in detailing the structures of the cholinesterases as the primary target site, progress with small molecule antidotes has yet to define a superior agent. Two major limitations are immediately apparent. T...

The effect of boletus polysaccharides on diabetic hepatopathy in rats.

The objective of this work was to investigate the effect of boletus polysaccharide (BPS) on diabetic hepatopathy in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats for the first time. The rats were fed with high-fat diet (HFD) for 4 weeks and induced with STZ by a single intraperitoneal injection to develop T2DM model. The HFD was given continually for another 4 weeks after diabetes induction, following the drugs of BPS (400 mg/kg bw/day) infused to stomach of rats once a day. After th...

Overview of novel multifunctional agents based on conjugates of γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and aminoadamantanes for treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative process whose effective treatment will require drugs that can act simultaneously on multiple pathogenic targets. Here, we present an overview of our previous multi-target studies of five groups of novel hybrid structures that combine, through spacers, five pharmacophores that have been found promising for AD treatment: γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and aminoadamantanes. Biological activity of the compounds was ...

An evolutionary perspective on the first disulfide bond in members of the cholinesterase-carboxylesterase (COesterase) family: Possible outcomes for cholinesterase expression in prokaryotes.

Within the alpha/beta hydrolase fold superfamily of proteins, the COesterase group (carboxylesterase type B, block C, cholinesterases…) diverged from the other groups through simultaneous integration of an N-terminal, first disulfide bond and a significant increase in the protein mean size. This first disulfide bond ties a large Cys loop, which in the cholinesterases is named the omega loop and forms the upper part of the active center gorge, essential for the high catalytic activity of these enzymes. In ...

Structural aspects of 4-aminoquinolines as reversible inhibitors of human acetylcholinesterase and butyrylcholinesterase.

Eight derivatives of 4-aminoquinolines differing in the substituents attached to the C(4)-amino group and C(7) were synthesised and tested as inhibitors of human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Both enzymes were inhibited by all of the compounds with inhibition constants (K) ranging from 0.50 to 50 μM exhibiting slight selectivity toward AChE over BChE. The most potent inhibitors of AChE were compounds with an n-octylamino chain or adamantyl group. The shortening of the chai...

Hesperidin, a citrus flavanone glycoside, accelerates the gastric healing process of acetic acid-induced ulcer in rats.

The flavonoid hesperidin is abundantly found in citrus fruits and is used to treat vascular diseases. Previous studies described its gastroprotective actions against stress or ethanol-induced ulcer in rodents; however, results from indomethacin-induced ulcer were controversy. Therefore, given its clinical use and contradictory findings in acute models, this study aims to evaluate the effect of hesperidin (1-10 mg/kg, p.o) on chronic gastric ulcer induced by acetic acid in rats, a model that resembles the ...

Mitochondrial and lysosomal dysfunction induced by the novel metal-insecticide Mg(hesp)(phen) in the zebrafish (Danio rerio) hepatocyte cell line (ZF-L).

The development of novel agrochemical compounds to reduce the use of pesticides with high ecological impact is urgently needed. A complex of Mg with two flavonoids hesperidin and phenanthroline [Mg(hesp)(phen)], referred to as MgHP, results in high insecticidal activity against urban, agricultural and forest insect pests. In vitro cytotoxicity biomarkers were used to assess the mechanism of action MgHP on fish cells, as this insecticide can reach the aquatic environment and affect its biota. The cytotoxic e...

Haplotypes of butyrylcholinesterase K-variant and their influence on the enzyme activity.

Butyrylcholinesterase (BChE) is a serine hydrolase widely distributed throughout the body. It provides protection against administrated or inhaled poisons by hydrolyzing or sequestering the toxic compounds. The most frequent genetic variant of BCHE gene - K variant (p.A539T) is located in the C-terminal tetramerization domain, outside of the catalytic center. Many studies tried to reveal the nature of the lower activity of BChE K-variant but results and conclusions were often contradictory. The aim of this ...

Phloretin loaded chitosan nanoparticles enhance the antioxidants and apoptotic mechanisms in DMBA induced experimental carcinogenesis.

The main aim of this study was to investigate the effects of phloretin loaded chitosan nanoparticles (PhCsNPs) on 7,12-dimethylbenz[a]anthracene (DMBA) induced experimental cancer in hamsters. Oral squamous cell carcinoma (OSCC) was induced in male golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Varying concentration of PhCsNPs (5, 10, and 20 mg/kg b.wt.) was orally administered on alternative days to evaluate the optimum dose. The experiment design was terminated at the...

Alpinoid C analog inhibits angiogenesis and induces apoptosis in COLO205 cell line.

Diarylheptanoids display an array of biological and pharmacological properties. We previously reported the synthesis of a diarylheptanoid Alpinoid c and a series of its derivatives, evaluated their cytotoxicity against various human cancer cells. We found some of these derivatives were significantly more potent than Alpinoid c in preventing the proliferation of various cancer cell lines. Among these, (S, E)-1-(3, 4 dimethoxy phenyl)-6-hydroxy-7-phenylhept-4-en-3-one (DPHP) showed most potent cytotoxicity ag...

Insights into the cardioprotective properties of n-3 PUFAs against ischemic heart disease via modulation of the innate immune system.

Ischemic heart diseases (IHD) is a major cause of cardiovascular death and disability worldwide. IHD is characterized by an imbalance between cardiac oxygen supply and demand predominantly due to obstruction of coronary arteries. Activation of the innate immune system and the consequent inflammatory response is an important contributor in the pathogenesis of IHD. An excessive and uncontrolled inflammatory response contributes to the adverse cardiac remodeling and fibrosis, making inflammation an important t...

Human mitochondrial carnitine acylcarnitine carrier: Molecular target of dietary bioactive polyphenols from sweet cherry (Prunus avium).

The effect of polyphenols, recognized as the principal antioxidant and beneficial molecules introduced with the diet, extracted from sweet cherry (Prunus avium) on the recombinant human mitochondrial carnitine/acylcarnitine transporter (CACT) has been studied in proteoliposomes. CACT transport activity, which was strongly impaired after oxidation by atmospheric O or HO due to the formation of a disulfide bridge between cysteines 136 and 155, was restored by externally added polyphenols. CACT reduction by po...

Activation of 20-HETE/PPARs involved in reno-therapeutic effect of naringenin on diabetic nephropathy.

Naringenin is a flavanone compound found in citrus fruits. Recent researches showed that naringenin has many potentially pharmacological effects. However, the therapeutic effect and the potential mechanism of naringenin on diabetic nephropathy (DN) remain to be elucidated. DN model was established by a high-fat diet combined with streptozotocin (STZ), which was confirmed by the levels of fasting blood glucose (FBG, more than 11.1 mmol/L) and urinary albumin (10 times higher than the normal mice). After 5 ...

Protection of the myocardium against ischemia/reperfusion injury by punicalagin through an SIRT1-NRF-2-HO-1-dependent mechanism.

Punicalagin has been found to exert cardiac protective effects against myocardial ischemia/reperfusion (MI/R) injury, although the detailed mechanisms remain largely unknown. This experiment was performed to explore the potential involvement of silent information regulator 1 (SIRT1)-NFE2-related factor 2 (NRF-2)-heme oxygenase-1 (HO-1) pathway in the cardiac protective actions of punicalagin. Sprague-Dawley (SD) rats were subjected to MI/R operation with or without punicalagin treatment (40 mg kgd). We ...


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