Perfluorooctane sulfonic acid (PFOS) is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets, and clothing. While its use in Europe, Canada, and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. However, epidemiologic evidence does not support a causal association between PFOS exposure and cancer risk in humans. However, in utero exposure to PFOS adversely affect the fetal synthesis and secretion of reproductive hormones (e.g., testosterone, estradiol, and inhibin B) in humans. Since the half-life of PFOS is relatively long, at 5.4-yr, even low-dose exposure to PFOS can accumulate in the body over an extended period of time. The mechanisms of PFOA -induced hepatic dysfunction are not completely understood but was shown, that PFOS induces their effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α) and thus altered its conformation. In addition, some recent experiments in vitro revealed, that PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

Perfluorooctane sulfonic acid (PFOS) is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets, and clothing. While its use in Europe, Canada, and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. However, epidemiologic evidence does not support a causal association between PFOS exposure and cancer risk in humans. However, in utero exposure to PFOS adversely affect the fetal synthesis and secretion of reproductive hormones (e.g., testosterone, estradiol, and inhibin B) in humans. Since the half-life of PFOS is relatively long, at 5.4-yr, even low-dose exposure to PFOS can accumulate in the body over an extended period of time. The mechanisms of PFOA -induced hepatic dysfunction are not completely understood but was shown, that PFOS induces their effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α) and thus altered its conformation. In addition, some recent experiments in vitro revealed, that PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

Muscarine or muscarin, a water-soluble toxin, which initially was isolated from the mushroom species Amanita muscar. Muscarine mimics the action of the acetylcholine by binding to the muscarinic acetylcholine receptors and acts as an agonist.

BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. BMS-345541 was identified as a selective inhibitor of the catalytic subunits of IKK (IKK-2 IC(50) = 0.3 uM, IKK-1 IC(50) = 4 uM). A binding model is proposed in which BMS-345541 binds to similar allosteric sites on IKK-1 and IKK-2, which then affects the active sites of the subunits differently. BMS-345541 was shown to have excellent pharmacokinetics in mice, and peroral administration showed the compound to dose-dependently inhibit the production of serum tumor necrosis factor alpha following intraperitoneal challenge with lipopolysaccharide. BMS-345541 is effective against NF-kappa B activation in mice and represents an important tool for investigating the role of IKK in disease models. BMS-345541 blocks both joint inflammation and destruction in collagen-induced arthritis in mice.

Chelidonine is the major alkaloid component of Chelidonium majus. Chelidonine is an isolate of Papaveraceae with acetylcholinesterase and butyrylcholinesterase (a nonspecific cholinesterase) inhibitory activity. It showed strong cytotoxicity in cancer cells. While several modes of death have been identified, most of anti-cancer attempts have focused on stimulation of cells to undergo apoptosis. Chelidonine seems to trigger multiple mechanisms in MCF-7 breast cancer cells. It induces both apoptosis and autophagy modes of cell death in a dose dependent manner. Alteration of expression levels of bax/bcl2, and dapk1a by increasing concentration of chelidonine approves switching the death mode from apoptosis induced by very low to autophagy by high concentrations of this compound. On the other hand, submicromolar concentrations of chelidonine strongly suppressed telomerase at both enzyme activity and hTERT transcriptional level. Long exposure of the cells to 50 nanomolar concentration of chelidonine considerably accelerated senescence. Altogether, chelidonine may provide a promising chemistry from nature to treat cancer. Chelidonine exhibits a broad spectrum of pharmacological properties, such as anti-inflammatory and antiviral activities Its biological activities and clinical applications have been extensively investigated. Especially the usage of chelidonine as an anticancer drug is very important lately. It also has profound inhibitory effects on airway inflammation, which means chelidonine can improve allergic asthma in mice and may also work for human medicine.

Perfluorooctane sulfonic acid (PFOS) is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets, and clothing. While its use in Europe, Canada, and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. However, epidemiologic evidence does not support a causal association between PFOS exposure and cancer risk in humans. However, in utero exposure to PFOS adversely affect the fetal synthesis and secretion of reproductive hormones (e.g., testosterone, estradiol, and inhibin B) in humans. Since the half-life of PFOS is relatively long, at 5.4-yr, even low-dose exposure to PFOS can accumulate in the body over an extended period of time. The mechanisms of PFOA -induced hepatic dysfunction are not completely understood but was shown, that PFOS induces their effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α) and thus altered its conformation. In addition, some recent experiments in vitro revealed, that PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

Genz-123346 is a potent and selective glucosylceramide synthase (GCS) inhibitor that blocks the conversion of ceramide to GL1. It has been studied as a potential treatment of diabetes mellitus, polycystic kidney disease and fatty liver disease. Genz-123346 improved glucose tolerance and increased insulin sensitivity in two animal models of type 2 diabetes. In Zucker diabetic fatty rats, treatment with Genz-123346 significantly lowered blood glucose levels and partially prevented the normal deterioration of pancreatic β-cell function over time and preserved the ability of the islets to secrete insulin. In the high-fat–fed diet-induced obese mice, Genz-123346 essentially normalized A1C levels to that of the lean animals. Inhibiting GSL synthesis ameliorates the liver pathology associated with obesity and diabetes in mice model. Blockade of kidney glucosylceramide GlcCer accumulation with the GCS inhibitor Genz-123346 effectively inhibits cystogenesis in mouse models orthologous to human autosomal dominant polycystic kidney disease (PKD) (Pkd1 conditional knockout mice) and nephronophthisis (jck and pcy mice). Molecular analysis in vitro and in vivo indicated that inhibition of GCS by Genz-123346 inhibited the AKT-mTOR signaling pathway. It induced autophagy via the AKT-mTOR signaling pathway in HEK293T cells, increased autophagy flux and reduced mutant α-syn levels in mouse primary neurons potentially via indendent mechanisms. Exposure of cells to Genz-123346 and to other GCS inhibitors at non-toxic concentrations can enhance the killing of tumor cells by cytotoxic anti-cancer agents. This chemosensitizing activity was unrelated to lowering intracellular glycosphingolipid levels. Genz-123346 is a substrate for multi-drug resistance efflux pumps such as P-gp (ABCB1, gP-170). In cell lines selected to over-express P-gp or which endogenously express P-gp, chemosensitization by Genz-123346 was primarily due to the effects on P-gp function. Genz-123346 has little effect on 1-O-acylceramide synthase activity at concentrations that effectively inhibit GL1 synthase activity and therefore do not significantly elevate cell ceramide levels in vitro. Unlike N-butyldeoxynojirimycin (NB-DNJ), another inhibitor of GCS Genz-123346 does not inhibit α-glucosidase or glucocerebrosidase.

(7AR)-7A-epi-Perindopril is an epimer (S, SR, SS) of the drug perindopril which is commonly used to treat high blood pressure, hypertension, heart failure, or stable coronary artery disease. This epimer possesses equal activity with the perindopril.

Perfluorooctane sulfonic acid (PFOS) is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets, and clothing. While its use in Europe, Canada, and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. However, epidemiologic evidence does not support a causal association between PFOS exposure and cancer risk in humans. However, in utero exposure to PFOS adversely affect the fetal synthesis and secretion of reproductive hormones (e.g., testosterone, estradiol, and inhibin B) in humans. Since the half-life of PFOS is relatively long, at 5.4-yr, even low-dose exposure to PFOS can accumulate in the body over an extended period of time. The mechanisms of PFOA -induced hepatic dysfunction are not completely understood but was shown, that PFOS induces their effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α) and thus altered its conformation. In addition, some recent experiments in vitro revealed, that PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.

2,3,5-Triphenyltetrazolium Chloride (TTC) is a redox indicator. In the TTC assay (also known as TTC test or tetrazolium test), TTC is used to differentiate between metabolically active and inactive tissues or cells. The white compound is enzymatically reduced to red TPF (1,3,5-triphenylformazan) in living tissues or cells due to the activity of various dehydrogenases (enzymes important in oxidation of organic compounds and thus cellular metabolism), while it remains as white TTC in areas of necrosis since these enzymes have been either denatured or degraded. TTC test is a reliable, sensitive, and specific adjunct in the examination of the human heart at necropsy to diagnose acute myocardial infarction in the human population. In addition TTC test may be used for diagnostics of bacteriuria.