GPX8 regulates clear cell renal cell carcinoma tumorigenesis through promoting lipogenesis by NNMT.

Background: Clear cell renal cell carcinoma (ccRCC), with its hallmark phenotype of high cytosolic lipid content, is considered a metabolic cancer. Despite the implication of this lipid-rich phenotype in ccRCC tumorigenesis, the roles and regulators of de novo lipid synthesis (DNL) in ccRCC remain largely unexplained.

Methods: Our bioinformatic screening focused on ccRCC-lipid phenotypes identified glutathione peroxidase 8 (GPX8), as a clinically relevant upstream regulator of DNL.

Highly conserved protein Rv1211 in Mycobacterium tuberculosis is a natively unfolded protein that binds to a calmodulin antagonist, trifluoperazine.

Rv1211 is a conserved hypothetical protein in Mycobacterium tuberculosis and is required for the growth and pathogenesis of the bacteria. The protein has been suggested as a calmodulin-like calcium-binding protein with an EF-hand motif and as a target of trifluoperazine, a calmodulin antagonist in eukaryotes that inhibits mycobacterial growth. Here, we expressed the recombinant protein of Rv1211 and performed structural and biochemical studies of Rv1211 and its interaction with Ca or trifluoperazine.

A Serum Marker for Early Pancreatic Cancer With a Possible Link to Diabetes.

Background: Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established.

Methods: Bioinformatics screening was performed for a serum PC marker.

Interaction between IDH1 WT and calmodulin and its implications for glioblastoma cell growth and migration.

Isocitrate dehydrogenase (IDH) mutations are found in low-grade gliomas, and the product of the IDH mutant (MT), 2-hydroxyglutarate (2-HG), is the first known oncometabolite. However, the roles of the IDH wild type (WT) in high-grade glioblastoma, which rarely has the IDH mutation, are still unknown. To investigate possible pathways related to IDH WT in gliomas, we carried out bioinformatics analysis, and found that IDH1 has several putative calmodulin (CaM) binding sites.

Artemisia Capillaris leaves inhibit cell proliferation and induce apoptosis in hepatocellular carcinoma.

Background: Natural product is one of the most important sources of drugs used in pharmaceutical therapeutics. Artemisia capillaris has been traditionally used as a hepatoprotective and anti-inflammatory agent. In this study, we extracted an ethanol fraction (LAC117) from the dried leaves of Artemisia capillaris and identified its anticancer activity and mechanism of action against hepatocellular carcinoma (HCC).

Prediction of glycated hemoglobin levels at 3 months after metabolic surgery based on the 7-day plasma metabolic profile.

Metabolic surgery has been shown to provide better glycemic control for type 2 diabetes than conventional therapies. Still, the outcomes of the surgery are variable, and prognostic markers reflecting the metabolic changes by the surgery are yet to be established. NMR-based plasma metabolomics followed by multivariate regression was used to test the correlation between the metabolomic profile at 7-days after surgery and glycated hemoglobin (HbA1c) levels at 3-months (and up to 12 months with less patients), and to identify the relevant markers.

Heteronuclear NMR as a 4-in-1 analytical platform for detecting modification-specific signatures of therapeutic insulin formulations.

Detecting possible modifications of therapeutic proteins is a critical element of the quality control of protein drugs. Typically, a number of techniques are used to evaluate different modifications of therapeutic protein formulations. Using heteronuclear NMR spectroscopy, we show that the difference between various insulin formulations can be detected "as is" with little pretreatment and quickly.

Effects of peribulbar anesthesia (sub-Tenon injection of a local anesthetic) on akinesia of extraocular muscles, mydriasis, and intraoperative and postoperative analgesia in dogs undergoing phacoemulsification.

Objective: To evaluate the effects of peribulbar anesthesia (sub-Tenon injection of lidocaine hydrochloride) on akinesia of extraocular muscles, mydriasis, and intraoperative and postoperative analgesia in dogs undergoing phacoemulsification.

Animals: 14 Beagles with ophthalmically normal eyes.

Procedures: A blinded randomized controlled trial was performed.

Characterization of the binding sites for the interactions between FKBP12 and intracellular calcium release channels.

FKBP12, an FK506 binding protein, interacts with type 1 ryanodine receptor (RyR1) and modulates its calcium channel activity. However, there are many opposing reports of FKBP12's interaction with other related calcium channels, such as type 1 IP(3) receptor and type 3 ryanodine receptor (IP(3)R1 and RyR3). In addition, the involvement of the prolyl-dipeptide motif in the calcium channels and the corresponding binding residues in FKBP12 remain controversial.

Global dynamic conformational changes in the suppressor domain of IP3 receptor by stepwise binding of the two lobes of calmodulin.

The roles of calmodulin (CaM) have been key points of controversy in the regulation of inositol-1,4,5-trisphosphate receptor (IP(3)R). To address the issue, we studied the interaction between CaM and the suppressor domain of IP(3)R, a key allosteric regulatory domain. First, by means of a pulldown and a fluorescence titration experiment, we confirmed the interaction.

Predicting idiopathic toxicity of cisplatin by a pharmacometabonomic approach.

Cisplatin has been one of the most widely used anticancer agents, but its nephrotoxicity remains a dose-limiting complication. Here, we evaluated the idiopathic nature and the predose prediction of cisplatin-induced nephrotoxicity using a nuclear magnetic resonance (NMR)-based pharmacometabonomic approach. Cisplatin produced serious toxic responses in some animals (toxic group), but had little effect in others (nontoxic group), as judged by hematological and histological results.

Differentiation of antlers from deer on different feeds using an NMR-based metabolomics approach.

Deer antler has been widely used as a dietary supplement for hundreds of years in Asian countries. The chemical composition of deer antlers strongly depends on the growth conditions of the deer, especially the feeds, but the effects of different feeds on deer antlers have not been studied. To expand our knowledge of the chemical constituents of deer antler and establish an efficient way of differentiating antlers obtained with different feeds, we applied an NMR-based metabolomics approach and OPLS-DA multivariate analysis.

A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer.

Background & Aims: Biliary tract cancer is highly lethal at presentation, with increasing mortality worldwide. Current diagnostic measures employing multiple criteria such as imaging, cytology, and serum tumor markers are not satisfactory, and a new diagnostic tool is needed. Because bile is a cognate metabolite-rich bio-fluid in the biliary ductal system, we tested a new metabolomic approach to develop an effective diagnostic tool.

Differentiation of cultivation sources of Ganoderma lucidum by NMR-based metabolomics approach.

Introduction: Ganoderma lucidum is a widely used and high-value medicinal natural product. Correct identification of its cultivation source is important for proper quality assurance, but is so far mostly dependent on subjective morphological examinations.

Objective: To develop an efficient way of discriminating the cultivation sources of Ganoderma lucidum, particularly those from Korea and China, the two major sources of the mushroom using NMR-based metabolomic differentiation.

Application of a 1H nuclear magnetic resonance (NMR) metabolomics approach combined with orthogonal projections to latent structure-discriminant analysis as an efficient tool for discriminating between Korean and Chinese herbal medicines.

Correct identification of the origins of herbal medical products is becoming increasingly important in tandem with the growing interest in alternative medicine. However, visual inspection of raw material is still the most widely used method, and newer scientific approaches are needed. To develop a more objective and efficient tool for discriminating herbal origins, particularly Korean and Chinese, we employed a nuclear magnetic resonance (NMR)-based metabolomics approach combined with an orthogonal projections to latent structure-discriminant analysis (OPLS-DA) multivariate analysis.

Effects of redox potential and Ca2+ on the inositol 1,4,5-trisphosphate receptor L3-1 loop region: implications for receptor regulation.

Inositol 1,4,5-trisphosphate receptor (IP(3)R) is a major intracellular Ca(2+) channel, modulated by many factors in the cytosolic and lumenal compartments. Compared with cytosolic control, lumenal-side regulation has been much less studied, and some of its mechanistic aspects have been controversial. Of particular interest with regard to lumenal regulation are whether it involves direct interactions between IP(3)R and the regulators, and whether it involves conformational changes of the lumenal regions of IP(3)R.

Distinct interactions between ubiquitin and the SH3 domains involved in immune signaling.

The SH3 domain is a versatile protein interaction motif that generally recognizes proline rich sequences (PRS). Recently, it has been shown that some SH3 domains in the endocytotic pathway can bind to ubiquitin. Moreover, Phe73 in the SH3 domain has been proposed to be an important determinant of the interaction, as the SH3 domains having Tyr73, either naturally or by mutation, failed to bind.

NMR-based metabolomics approach for the differentiation of ginseng (Panax ginseng) roots from different origins.

Agro-herbal materials vary in prices and qualities depending on the origin and age and the differentiation is both scientific and public health issue. Here, we describe a metabolomics approach used to discriminate ginseng roots from different sources. Six different types of ginseng roots from China and Korea were analyzed by NMR-based metabolomics.

Identification of residues participating in the interaction between an intraluminal loop of inositol 1,4,5-trisphosphate receptor and a conserved N-terminal region of chromogranin B.

The inositol 1,4,5-trisphosphate receptor (IP3R) is a membrane channel that conducts calcium ions from the intracellular calcium stores. Despite a wealth of information on the cytoplasmic regulation of the IP3R, little is known about its regulation on the luminal side of the calcium stores. Here, we report studies on the IP3R intraluminal loop L3-2 and a conserved N-terminal region of chromogranin B.

Recombinant preparation and characterization of interactions for a calmodulin-binding chromogranin A peptide and calmodulin.

Chromogranin-derived peptides have important and varied biological activities. They affect a wide spectrum of targets such as fungal membranes, blood vessels, myocardial cells, and pancreatic cells. Despite the biological significance and the diverse activities, the molecular mechanisms of the interactions between the peptides and the target proteins have not been well understood.