Concentration Of F2 Research Articles

FORMULASI DAN EVALUASI KESTABILAN FISIK SEDIAAN MASKER GEL PEEL-OFF DARI SARI BUAH LEMON CUI (Citrus microcarpa Bunge.)

Lemon cui also known as fish lemon or kalamansi lemon is known to contain one of them vitamin C which has the potential as an antioxidant so that it can be applied as active ingredient in peel off mask preparations. The aims of this study weretoobtaining the best PVA concentration in the manufacture of peel-off gel masks from lemon cui juice that meet the stability test requirements. physique. The method of making a sample of lemon cui juice is obtained by grinding it using a blender, adding 100 mL of water and then separating the pulp to obtain the juice. The formulation of peel-off gel mask preparations uses variations in the concentration of PVA (Polyvinyl Alcohol), namely F1 (10%), F2 (13%) and F3 (16%). Physical stability tests included organoleptic tests, homogeneity tests, spreadability tests, pH tests, adhesion tests and drying time tests.The results showed that the preparations F1, F2 and F3 showed physical stability based on the results of organoleptic tests, homogeneity tests, spreadability tests, pH tests, adhesion tests and drying time tests before and after accelerated storage conditions. Based on the test results obtained, it can be concluded that the formulation of the Lemon Cui peel-off gel mask preparation from the three concentrations of PVA met the requirements for physical stability. The best PVA concentration is 10% because it has the best dry time.

Formulation and Pharmaceutical Quality Evaluation of Tablets Containing Extract of Cinnamomum burmannii BARK and Colocasia esculenta (L) Schott Leaves

Cinnamon bark (Cinnamomum burmannii) is used traditionally and has an ingredient containing cinnamic acid compounds. Colocasia esculenta (L) Schott leaves contains of flavonoids, alkaloids, tannins, saponins, steroids, and terpenoids. Both of the plants C. esculenta and C. burmannii plants have the potential as anti-diabetics because they can lower blood glucose levels. This study aims to make combination tablets of C. burmannii bark and C. esculenta leaves extract with various concentrations of PVP K30 binder. This research made four formulas with the concentration of PVP K30, namely F1 (2%), F2 (3%), F3 (4%), and F4 (5%). Tablet preparations were prepared by the wet granulation method. Tablet analysis used flavonoids quercetin and cinnamic acid as markers. The results showed that the tablets were flat, round in shape, light green, had a slightly bitter taste, and had a distinctive aromatic odor. The differences in the concentration of PVP K30 binder 2-5% could affect the hardness, friability, disintegration time, and tablet dissolution (p<0.05). The tablet's hardness was 3.65-5.01 KP; friability was 0.705%, disintegration time was <15 minutes, and dissolution was 84.61% in 40 minutes. The levels of the flavonoid quercetin in the tablets were 4.21% and 8.03% cinnamic acid. A tablet combination of C. burmannii bark and C. esculenta leaves extract with a PVP K30 concentration of 5% (F4) has the best quality.

Differential expression of coagulation pathway-related proteins in diabetic urine exosomes

BackgroundCoagulation function monitoring is important for the occurrence and development of diabetes. A total of 16 related proteins are involved in coagulation, but how these proteins change in diabetic urine exosomes is unclear. To explore the expression changes of coagulation-related proteins in urine exosomes and their possible roles in the pathogenesis of diabetes, we performed proteomic analysis and finally applied them to the noninvasive monitoring of diabetes.MethodsSubject urine samples were collected. LC-MS/MS was used to collect the information on coagulation-related proteins in urine exosomes. ELISA, mass spectrometry and western blotting were used to further verify the differential protein expression in urine exosomes. Correlations with clinical indicators were explored, and receiver operating characteristic (ROC) curves were drawn to evaluate the value of differential proteins in diabetes monitoring.ResultsAnalyzing urine exosome proteomics data, eight coagulation-related proteins were found in this study. Among them, F2 was elevated in urine exosomes of diabetic patients compared with healthy controls. The results of ELISA, mass spectrometry and western blotting further verified the changes in F2. Correlation analysis showed that the expression of urine exosome F2 was correlated with clinical lipid metabolism indexes, and the concentration of F2 was strongly positively correlated with blood TG levels (P < 0.05). ROC curve analysis showed that F2 protein in urine exosomes had a good monitoring value for diabetes.ConclusionCoagulation-related proteins were expressed in urine exosomes. Among them, F2 was increased in diabetic urine exosomes and may be a potential biomarker for monitoring diabetic changes.

Fraction distribution of cadmium in surface sediment collected from bivalve species harvesting areas in Binh Thuan province (Tuy Phong, Phan Thiet, Lagi)

This paper aims to provide information about the fractions of cadmium (Cd) and its distribution in surface sediment collected from bivalves harvesting areas in Binh Thuan province (Tuy Phong, Phan Thiet, Lagi). For this purpose, the sediment samples were collected monthly along with these areas in 2015–2016. To analyze the fractions of Cd, a five-step Tessier (1979) sequential extraction process was used, including Fraction 1 (Exchangeable), Fraction 2 (Bound to carbonate), Fraction 3 (Bound to iron-manganese oxide), Fraction 4 (Bound to organic compounds), and Fraction 5 (Residual). The research showed that Cd concentrations contributed mainly to a strong association residual fraction (Fraction 5). However, the percentage of Cd in total Fraction 1 and Fraction 2 (high mobility and bioavailability fractions) in all areas was also relatively high. In the Tuy Phong and Lagi harvesting areas, the sediment distribution follows the trend of F5 &gt; F2 &gt; F3 &gt; F4 &gt; F1, while the trend present in sediment in the Phan Thiet harvesting area follows F2 &gt; F5 &gt; F3 &gt; F1 &gt; F4. The Fractions F1, F4, and F5 indicated a weak positive correlation with the total concentration of Cd, while F3 and F2 indicated medium and strong correlations, respectively. According to the Risk Assessment Code (RAC), the results reveal that Cd poses a high environmental risk in this area.

Formulation of Hand Cream Essential Oil of Basil (Ocimum basilicum) Leaves

Basil (Ocimum basilicum) leaf essential oil contains terpenoid compounds that have antibacterialactivity. This study aims to obtain hand cream preparations of basil essential oil, as well as to determinethe effect of concentration variation of liquid paraffin on the results of the evaluation of the preparation.In this study, three formulations of hand cream preparations of basil essential oil were made withthree variations in the concentration of liquid paraffin, namely F1 (9%), F2 (10%), and F3 (11%).Furthermore, the preparation was evaluated for 28 days at room temperature (15-300C) and humidity(60-80%) which included organoleptic, pH, viscosity, homogeneity, spreadability, and type of emulsion.The results showed that formulas F1, F2, and F3 met all the requirements of organoleptic, pH, viscosity,homogeneity, spreadability, and type of emulsion. The results of the statistical analysis showed thatvariations in liquid paraffin concentrations had a significant effect (p&lt;0.05) on the evaluation ofviscosity and did not significantly affect the evaluation of organoleptic, evaluation of pH, evaluation ofhomogeneity, evaluation of spreadability, and evaluation of emulsion type.

A Comprehensive Approach to Investigating Fluorine-Bearing Gas Mixtures

An integrated method is proposed for examining the compositions of fluorine-bearing gaseous mixtures, which allows for determining the concentration of HF, F2, N2, O2, CO2, CF4, and C2F6 in these mixtures. The concentration of hydrogen fluoride is determined by its sorption on sodium fluoride followed by the determination of the fluoride ion by the potentiometric method. The lower threshold of determination of hydrogen fluoride is found to be 0.09 vol.%. The concentrations of N2, O2, CO2, CF4, and C2F6 are determined by the gas chromatographic method using a thermal conductivity detector. The proposed gas-chromatography method offers a quantitative measurement of the concentration of N2, O2, CO2, CF4, and C2F6 at the lower limits of detection of 0.008, 0.012, 0.011, 0.009, and 0.019 vol.%, respectively. Based on the developed method, the compositions of a standard fluorine-nitrogen (10 vol.%) and anodic gas samples, synthesized in a laboratory electrolyzer at the National Research Tomsk Polytechnic University and in an industrial electrochemical reactor at JSC Siberian Chemical Plant (Russia), are studied.

Counting Point Defects at Nanoparticle Surfaces by Electron Holography

Metal oxide nanoparticles exhibit outstanding catalytic properties, believed to be related to the presence of oxygen vacancies at the particle's surface. However, little quantitative information is known about concentrations of point defects inside and at surfaces of these nanoparticles, due to the challenges in achieving an atomically resolved experimental access. By employing off-axis electron holography, we demonstrate, using MgO nanoparticles as an example, a methodology that discriminates between mobile charge induced by electron beam irradiation and immobile charge associated with deep traps induced by point defects as well as distinguishes between bulk and surface point defects. Counting the immobile charge provides a quantification of the concentration of F2+ centers induced by oxygen vacancies at the MgO nanocube surfaces.

Inference of a “Hot Ice” Layer in Nitrogen-Rich Planets: Demixing the Phase Diagram and Phase Composition for Variable Concentration Helium–Nitrogen Mixtures Based on Isothermal Compression

Van der Waals (vdW) chemistry in simple molecular systems may be important for understanding the structure and properties of the interiors of the outer planets and their satellites, where pressures are high and such components may be abundant. In the current study, Raman spectra and visual observation are employed to investigate the phase separation and composition determination for helium-nitrogen mixtures with helium concentrations from 20 to 95% along the 295 K isothermal compression. Fluid-fluid-solid triple-phase equilibrium and several equilibria of two phases including fluid-fluid and fluid-solid have been observed in different helium-nitrogen mixtures upon loading or unloading pressure. The homogeneous fluid in helium-nitrogen mixtures separates into a helium-rich fluid (F1) and a nitrogen-rich fluid (F2) with increasing pressure. The triple-phase point occurs at 295 K and 8.8 GPa for a solid-phase (N2)11He vdW compound, fluid F1 with around 50% helium, and fluid F2 with 95% helium. Helium concentrations of F1 coexisted with the (N2)11He vdW compound or δ-N2 in helium-nitrogen mixtures with different helium concentrations between 40 and 50% and between 20 and 40%, respectively. In addition, the helium concentration of F2 is the same in helium-nitrogen mixtures with different helium concentrations and decreases upon loading pressure. Pressure-induced nitrogen molecule ordering at 32.6 GPa and a structural phase transition at 110 GPa are observed in (N2)11He. In addition, at 187 GPa, a pressure-induced transition to an amorphous state is identified.

FORMULASI SEDIAAN ANTIOKSIDAN FACIAL WASH EKSTRAK METANOL DAUN GANITRI (Elaeocarpus ganitrus Roxb.) DENGAN VARIASI SODIUM LAURIL SULFAT SEBAGAI SURFAKTAN

Ganitri leaves (Elaeocarpus ganitrus Roxb.) contain flavonoid compounds that function as antioxidants. Antioxidants in cosmetics are used to prevent skin damage due to exposure to free radicals. Facial Wash is a cosmetic preparation to help remove dead skin cells, rejuvenate the skin, remove dirt, oil and provide moisture. This study aims to obtain a facial wash formula that has good characteristics and is effective as an antioxidant by varying the concentration of sodium lauryl sulfate, namely F1 (0.25%), F2 (0.5%) and F3 (1%) as surfactant. The results showed that variations in SLS concentration had a significant effect on the physical evaluation of the preparation with a p value of &lt;0.05. Formula 3 (SLS 1%) provides the best facial wash characteristics with the results of the test parameters meeting the standards. The results of the antioxidant activity test showed that formula 3 had an IC50 value of 17.36 ppm which was categorized as very strong with ascorbic acid as a comparison of 10.70 ppm and a negative control of 54.11 ppm.

Peel-off Kefir Mask Arachi (Arachis hypogaea L.): Characterization and Antioxidant Activity

This study aims to determine the best formulation for the peel-off mask Arachi or peanut (Arachis hypogaea L). Arachis hypogaea kefir as an active ingredient is added with variations in the concentration of F1 (0.5%) and F2 (2%) (w/v). Organoleptic tests, homogeneity, dry time, and pH were carried out on the peel-off mask that had been made. Antioxidant test (DPPH methods) was performed on masks F1 and F2. The results showed that the peel-off mask of A. hypogaea kefir had the best antioxidant activity at a concentration of 2% (F2) kefir with an IC50 value of 1.865 ppm and was very active. The characteristics of the peel-off mask have good physical stability, proven by not experiencing a change in color, odor, being homogeneous, having good dispersion power, and having a dry time ranging from 10-23 minutes. The pH value of the peel-off mask preparation is 4.52, and it is appropriate with SNI and the pH balance of normal human skin. The peel-off mask of A. hypogaea kefir can be produced because has good physical stability and antioxidant activity.

FORMULATION AND EVALUATION OF PEEL OFF GEL FACIAL MASK FROM ARABICA COFFEE FRUIT PEEL EXTRACT (COFFEA ARABICA L.)

Objective: The aim of this study was to obtain a peel off gel facial mask preparation from Arabica coffee fruit peel extract that meets the requirements and to determine the antioxidant activity of Arabica coffee fruit peel extract and peel off gel facial mask preparation from coffee fruit peel extract&#x0D; Methods: In this study, three formulations of peel off gel facial mask were made with 3 variations in the concentration of coffee fruit peel extract, namely F1 (1%), F2 (2%), and F3 (3%). Furthermore, the preparation was evaluated for 28 d of storage at room temperature (25-30 °C) and cold temperature (8 °C) which included organoleptic, pH, spreading ability, homogeneity, viscosity, dry time, and antioxidant activity.&#x0D; Results: The results of the evaluation showed that F1, F2, and F3 met the requirements which included organoleptic, pH, spreading ability, homogeneity, viscosity, and dry time. The antioxidant activity of the coffee fruit peel extract was very strong (IC50 17.36 µg/ml). The antioxidant activity in the peel off gel facial mask sample of formula F1 (IC50 75.63 µg/ml) and formula F2 (IC50 50.71 µg/ml) was strong, and for formula F3 was very strong (IC50 21.44 µg/ml).&#x0D; Conclusion: All formulas met the evaluation requirements, arabica coffee fruit peel extract and peel of gel facial mask preparation (F3) have very strong antioxidant activity.

Canonical and Non-Canonical Roles of PFKFB3 in Brain Tumors.

PFKFB3 is a bifunctional enzyme that modulates and maintains the intracellular concentrations of fructose-2,6-bisphosphate (F2,6-P2), essentially controlling the rate of glycolysis. PFKFB3 is a known activator of glycolytic rewiring in neoplastic cells, including central nervous system (CNS) neoplastic cells. The pathologic regulation of PFKFB3 is invoked via various microenvironmental stimuli and oncogenic signals. Hypoxia is a primary inducer of PFKFB3 transcription via HIF-1alpha. In addition, translational modifications of PFKFB3 are driven by various intracellular signaling pathways that allow PFKFB3 to respond to varying stimuli. PFKFB3 synthesizes F2,6P2 through the phosphorylation of F6P with a donated PO4 group from ATP and has the highest kinase activity of all PFKFB isoenzymes. The intracellular concentration of F2,6P2 in cancers is maintained primarily by PFKFB3 allowing cancer cells to evade glycolytic suppression. PFKFB3 is a primary enzyme responsible for glycolytic tumor metabolic reprogramming. PFKFB3 protein levels are significantly higher in high-grade glioma than in non-pathologic brain tissue or lower grade gliomas, but without relative upregulation of transcript levels. High PFKFB3 expression is linked to poor survival in brain tumors. Solitary or concomitant PFKFB3 inhibition has additionally shown great potential in restoring chemosensitivity and radiosensitivity in treatment-resistant brain tumors. An improved understanding of canonical and non-canonical functions of PFKFB3 could allow for the development of effective combinatorial targeted therapies for brain tumors.

FORMULASI EMULGEL EKSTRAK ETANOL DAUN JAMBU BIJI (Psidium guajava Linn.) SEBAGAI ANTI ACNE CLEANSER

ABSTRACT&#x0D; &#x0D; Acne is a major problem for teenagers, especially at puberty. Guava leaves (Psidium guajava Linn .) are&#x0D; plants that contain several secondary metabolites, including the tannins, triterpenoids, glycosides, and&#x0D; flavonoids, which have anti-acne activity. So far, acne reduction is still being done using synthetic cosmetics.&#x0D; However, synthetic cosmetics often irritate, so that herbal cosmetics are an alternative. Formulation of&#x0D; herbal cosmetics for acne need to do. This study aims to determine the best formula for anti-acne cleanser&#x0D; emulgel from the ethanol extract of guava leaves based on the physical evaluation. Guava leaf extract as&#x0D; obtained by the maceration method uses ethanol as a solvent, then an emulgel was prepared with an extract&#x0D; concentration of F1 (5%) and F2 (10%). Emulgel characteristics were determined by physical evaluation&#x0D; including organoleptic, pH, emulsion type, viscosity, spreadability, homogeneity, foam stability, power clean,&#x0D; and hedonism. The best formula was determined by the number of tests that meet the requirements and are&#x0D; liked by consumers. The results had shown F1 is the best formula based on physical evaluation.&#x0D; &#x0D; Keywords: Acne, emulgel, guava leaves, physical evaluation

Optimasi Formula Spray Gel Ekstrak Bawang Tiwai (Eleutherine americana (Aubl) Merr)

The ethanolic extract from the bulb of Eleutherine americana has the potential for anti-inflammatory activity to be developed into a preparation that is a practical spray gel to use. The aim of this study is to made a spray gel containing ethanolic extract from the bulb of Eleutherine americana. Spray gel preparation was prepared by varying the concentration of Carbopol as a gelling agent with a concentration of F1 (0.4%), F2 (0.6%), and F3 (0.8%) with active substances and evaluated physical stability. Data from the results of physical stability testing in statistical analysis. Organoleptic test results and homogenity of ethanolic extract from the bulb of Eleutherine americana spray gel from all formulas showed stable, pH was in the range of 5.2-6.1 and Viscosity in formulas 1, 2, and 3 were respectively 0.65-1323 (Pa.s ) this condition is still within the range of viscosity of spray gel formulation, and have a spread pattern. While the formula 2 and 3, the viscosity is not eligible.

Removal of bacteriophage f2 in water by Fe/Ni nanoparticles: Optimization of Fe/Ni ratio and influencing factors

Pathogenic viruses in water are seriously harmful to human health and highly resistant to conventional disinfections. As a kind of promising attempts for pollution remediation, Fe-based nanoparticles show excellent performance in removing contaminants. In this study, the Fe/Ni nanoparticles (Fe/Ni NPs) were synthesized using the self-designed device and used for bacteriophage inactivation in water. Scanning electron microscope (SEM) and X-ray diffraction (XRD) showed that the as-prepared Fe/Ni particles were spherical and the average particle size was 93 nm. The synthesized Fe/Ni NPs achieved much higher removal efficiency of bacteriophage f2 than nanoscale zero-valent iron (nZVI), while Ni nanoparticles (Ni NPs) showed no removal effect on the bacteriophage f2. The highest removal efficiency of bacteriophage f2 by Fe/Ni NPs was obtained when the primary ratio of Fe:Ni was 5:1. In addition, the removal efficiency of phage f2 under aerobic condition was significantly higher than that under anaerobic condition with Fe/Ni NPs, and the role of Ni was proved as a catalyst in the system. Besides, the effect of initial pH, initial concentration of bacteriophage f2, particles dose, rotation rate, and temperature on the removal efficiency of bacteriophage f2 were studied. The result showed that the removal efficiency of bacteriophage f2 did not change obviously in the test pH range (5–8), and was positively related with the rotation rate and negatively related with the initial concentration of bacteriophage f2. The particles dose could increase the removal efficiency of phage f2, but the removal efficiency would decrease when the dose was too much due to the aggregation of nanoparticles. The increase of temperature could increase the removal efficiency initially, but decrease the removal efficiency finally due to the accelerated corrosion of iron.

Korelasi Berat Badan dan Umur Sapi terhadap Berat, Volume Cairan dan Konsentrasi Prostaglandin F2α pada Vesikula Seminalis

Seminal vesicles were collected from 60 heads of Bulls which butchered in slaughter house (RPH) Yogyakarta. The aims of this study are knowing the relationship between body weight, age, fluids volume and concentration of prostaglandin F2 α (PGF2α) in seminal vesicle of beef cattle. Those seminal vesicles were gathered from bulls which recorded its body weight and age then measured its seminal vesicles for weight, fluids volume and PGF2α levels. The PGF2α level was measured by Enzyme-Linked Immunosorbent Assay. Statistical analysis was performed using one way – analysis of varian, regression and correlation with P&lt;0.05. Body weight of bulls showed positive correlation with the weight of seminal vesicle and its fluids volume. However, PGF2α levels were not correlated with the body weight of cattle. Weight of seminal vesicles also exhibited positive correlation with volume of vesicle fluids but no correlation with PGF2α levels. Based on the age of bulls, there were no correlation withthe weight of seminal vesicles, seminal fluids volume and PGF2α levels. Those result indicated that the weight and fluids volume were affected by the body weight of bulls altough the PGF2α levels have a standard of developmentwhich seems affected by other factors such as concentration of androgen hormone.

Diabetes and risk of cancer

Recent epidemiological studies have revealed the association of elevated cancer risk and diabetes mellitus [1–13]. Because the prevalence of diabetes mellitus and cancer is increasing worldwide, understanding the higher risk of specific types of cancer is important in management of diabetic patients. The American Diabetes Association (ADA) and the American Cancer Society (ACS) produced a consensus report on the increased risk of liver, pancreas, endometrial, colorectal, breast, and bladder cancer among diabetic patients [14]. In 2013, the joint committee of the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) reported the association of diabetes and cancer, including colorectal, liver, and pancreatic cancer, among Japanese diabetic patients [15]. Although the mechanisms underlying this association are not fully understood, several potential mechanisms which promote oncogenesis in diabetes have been discussed. Chronic inflammation, insulin resistance associated with hyperinsulinemia, and hyperglycemia have been suggested as potential mechanisms. These factors may lead to increased risk of cancer in diabetes and promote oncogenesis in different ways. Numerous studies have suggested the effect of insulin and chronic inflammation on cancer progression in diabetes. The experimental and epidemiological evidence is most consistent with the hyperinsulinemia and chronic inflammation hypothesis. In particular, progression of hepatocellular carcinoma seems to be closely associated with chronic inflammation and insulin resistance related to hyperinsulinemia. In a large scale cohort study in Japan, diabetes led to a high risk of hepatocellular carcinoma [16]. A meta-analysis also showed that diabetes increases the risk of hepatocellular carcinoma [12] and diabetes is risk factor for hepatocellular carcinoma among patients with nonalcoholic fatty liver disease (NAFLD) [17]. A recent clinical review suggested that NAFLD and nonalcoholic steatohepatitis (NASH) patients, especially those with diabetes, should be monitored for the onset of hepatocellular carcinoma [18]. However, the involvement of hyperglycemia in cancer development is less clear and few studies have shown the contribution of hyperglycemia to cancer progression and metastasis. Cancer cells maintain an abnormally high rate of glycolysis, even in the presence of oxygen, a phenomenon called the Warburg effect [19]. Enhanced glucose uptake in cancer is revealed by positron emission tomography (PET) scans, a widely used method of cancer detection, and clinical use of PET scans is well established. Despite many years of investigation, the specific regulatory mechanisms responsible for the Warburg effect are not fully understood. Increased expression of glucose transporter 1 has been observed, and this enables cancer cells to absorb extracellular glucose [20]. Increased type 2 hexokinase activity in cancer has also been demonstrated [21–23]. Although hexokinase is involved in the first irreversible stage of glycolysis, it is not the late limiting enzyme of the process. Fructose 2,6-bisphosphate (F2,6BP) is a powerful allosteric activator of 6-phosphofructo-1-kinase (PFK-1), which is the rate-limiting enzyme of glycolysis [24]. F2,6BP increases the affinity of PFK-1 for fructose 6-phosphate and reduces the inhibitory effect of ATP. Previous work has revealed markedly elevated levels of F2,6BP in several cancer cell lines [25–27]. The intracellular concentration of F2,6BP depends on the activity of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose2,6-bisphosphatase (PFK-2/FBPase) [28]. At least four & Toshiya Atsumi tatsumi@nissei-hp.com

Abstract CT206: PFK-158, first-in-man and first-in-class inhibitor of PFKFB3/ glycolysis: A phase I, dose escalation, multi-center study in patients with advanced solid malignancies

Abstract Metabolic alterations in cancer have been recognized as important novel targets, especially glycolysis. Over-expression of HIF-1α, activation of Ras, AKT or PI3K, loss of p53 or PTEN are associated with the development of human cancers and converge on glycolysis by activating PFKFB3, a bifunctional enzyme. This enzyme interconverts fructose-6-phosphate (F6P) to fructose-2,6-bisphosphate (F2,6BP) and F2,6BP is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1), a rate-limiting enzyme and control point in the glycolytic pathway. PFKFB3 is of particular interest since it controls the intracellular concentration of F2,6BP, is required for tumorigenic growth and it has been found to be activated in human cancer cell lines and tumors, to be increased by hypoxic exposure via HIF-1α and by several oncogenes and mutations. PFK-158 is a potent and selective inhibitor of PFKFB3 that is currently being investigated in a phase I study in patients with advanced solid malignancies. PFK-158 is: (i) is a nanomolar inhibitor of recombinant PFKFB3; (ii) inhibits PFKFB3 activity and glycolysis in cancer cells; (ii) is well tolerated in vivo; and (iv) is very effective in multiple preclinical mouse models of human-derived tumors and syngeneic murine models. IND-enabling safety and toxicity studies demonstrated that PFK158 is well tolerated in rats and dogs and supported the initiation of a phase I trial that is now underway. The primary objective of the study is to describe the dose limiting toxicity and to determine either the maximum tolerated dose or biological effective dose of PFK-158 in a “3+3” cohort-based dose escalation design that follows a modified Fibonacci scheme. The pharmacokinetic profile of PFK-158 will also be determined. Multiple secondary endpoints have been incorporated to assess the effects of PFK-158 on peripheral blood mononuclear cell (F6P; F2,6BP; 14C-2-dexoyglucose uptake) and on glucose uptake using FDG-PET imaging. This trial, opened at two US sites, is currently enrolling Cohort 3 (96 mg/m2). Prior cohorts (24 and 48 mg/m2) have been completed without dose-limiting toxicities or drug-related significant adverse events. Of the patients enrolled to date, a patient of Cohort 1 was on study for 6 cycles during which his overall hepatic metastatic tumor burden decreased. In addition, numerous publications demonstrated that over-expression of HIF-1α, activation of Ras, AKT or PI3K, loss of p53 or PTEN converge on glycolysis by activating PFKFB3. Results of preclinical studies show that combination of PFK-158 with targeted agents, which indirectly activate glycolysis, leads to clear therapeutic benefits. In conclusion, PFK158 is the first-in-man and first-in-class PFKFB3 inhibitor to be examined in a phase I trial and may have significant clinical utility either as a monotherapy or when combined with targeted agents. Citation Format: Rebecca Redman, Paula Pohlmann, Michael Kurman, Gilles H. Tapolsky, Jason Chesney. PFK-158, first-in-man and first-in-class inhibitor of PFKFB3/ glycolysis: A phase I, dose escalation, multi-center study in patients with advanced solid malignancies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT206. doi:10.1158/1538-7445.AM2015-CT206

Bioconversion of Ginsenosides from Red Ginseng Extract Using Candida allociferrii JNO301 Isolated from Meju

Red ginseng (Panax ginseng), a Korean traditional medicinal plant, contains a variety of ginsenosides as major functional components. It is necessary to remove sugar moieties from the major ginsenosides, which have a lower absorption rate into the intestine, to obtain the aglycone form. To screen for microorganisms showing bioconversion activity for ginsenosides from red ginseng, 50 yeast strains were isolated from Korean traditional meju (a starter culture made with soybean and wheat flour for the fermentation of soybean paste). Twenty strains in which a black zone formed around the colony on esculin-yeast malt agar plates were screened first, and among them 5 strains having high β-glucosidase activity on p-nitrophenyl-β-D-glucopyranoside as a substrate were then selected. Strain JNO301 was finally chosen as a bioconverting strain in this study on the basis of its high bioconversion activity for red ginseng extract as determined by thin-layer chromatography (TLC) analysis. The selected bioconversion strain was identified as Candida allociferrii JNO301 based on the nucleotide sequence analysis of the 18S rRNA gene. The optimum temperature and pH for the cell growth were 20~30°C and pH 5~8, respectively. TLC analysis confirmed that C. allociferrii JNO301 converted ginsenoside Rb1 into Rd and then into F2, Rb2 into compound O, Rc into compound Mc1, and Rf into Rh1. Quantitative analysis using high-performance liquid chromatography showed that bioconversion of red ginseng extract resulted in an increase of 2.73, 3.32, 33.87, 16, and 5.48 fold in the concentration of Rd, F2, compound O, compound Mc1, and Rh1, respectively.

Generation mean analysis of spring wheat (Triticum aestivum L.) seedlings tolerant to high levels of manganese

Effective utilisation of wheat (Triticum aestivum L.) germplasm tolerant to high manganese (Mn) in a breeding program requires an understanding of the genetics of Mn tolerance. Five wheat cultivars differing in their response to high Mn were crossed in a half diallel design with no reciprocals. Seedlings of parents and progeny generations were phenotyped in high Mn nutrient solutions. Total chlorophyll concentration, which was positively correlated with leaf elongation rate during recovery from Mn stress, was used for phenotyping Mn tolerance. Means of chlorophyll concentration of P1, P2, F1, F2, BC1, and BC2 generations, in all crosses which showed significant variation among generations, were subjected to line crosses analysis to estimate gene effects. The continuous frequency distribution of seedlings with differential Mn tolerance, the similarity of the F1 and F2 means, and the high and significant levels of additive gene action indicated quantitative inheritance for Mn tolerance at seedling stage. A preponderance of additive effects indicated that selection for Mn tolerance in early generations should be effective.