FXYD3: A Promising Biomarker for Urothelial Carcinoma

Objective Urothelial carcinoma (UC) of the kidney is a relatively rare but aggressive form of kidney cancer. Differential diagnosis of renal UC from renal cell carcinoma (RCC) can be difficult, but is critical for correct patient management. We aimed to use global gene expression profiling to identify genes specifically expressed in urothelial carcinoma (UC) of the kidney, with purpose of finding new biomarkers for differential diagnosis of UC of both upper and lower tract from normal tissues. Materials and Methods Microarray gene expression profiling was performed on a variety of human kidney tumor samples, including clear cell, papillary, chromophobe, oncocytoma, renal UC and normal kidney controls. Differentially expressed mRNAs in various kidney tumor subtypes were thus identified. Protein expression in human UC tumor samples from both upper and lower urinary tract was evaluated by immunohistochemistry. Results FXYD3 (MAT-8) mRNA was specifically expressed in UC of the kidney and not in normal kidney tissue or in any RCC tumor subtypes. FXYD3 mRNA levels displayed equal or better prediction rate for the detection of renal UC than the mRNA levels of selected known UC markers as p63, vimentin, S100P, KRT20 and KRT7. Finally, immunohistochemical staining of clinical UC samples showed that FXYD3 protein is overexpressed in majority of UC of the upper genitourinary tract (encompassing the kidney, ~90%) and in majority of high grade bladder UC (~84%, it's < 40% in low grade tumors, P < 0.001) compared to normal kidney and bladder tissues. Conclusion FXYD3 may be a promising novel biomarker for the differential diagnosis of renal UC and a promising prognosis marker of UC from bladder. Because it was identified genome-widely, FXYD3 may have important biological ramifications for the genetic study of UC

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells

Curcumin loaded pH-sensitive hybrid lipid/block copolymer nanosized drug delivery systems

Curcumin is a perspective drug candidate with pleiotropic antineoplastic activity, whose exceptionally low aqueous solubility and poor pharmacokinetic properties have hampered its development beyond the preclinical level. A possible approach to overcome these limitations is the encapsulation of curcumin into nano-carriers, incl. liposomes. The present contribution is focused on feasibility of using hybrid pH-sensitive liposomes, whereby curcumin is entrapped as a free drug and as a water soluble inclusion complex with PEGylated tert-butylcalix[4]arene, which allows the drug to occupy both the phospholipid membranes and the aqueous core of liposomes. The inclusion complexes were encapsulated in dipalmithoylphosphathydilcholine:cholesterol liposomes, whose membranes were grafted with a poly(isoprene-b-acrylic acid) diblock copolymer to confer pH-sensitivity. The liposomes were characterized by DLS, ζ-potential measurements, cryo-TEM, curcumin encapsulation efficacy, loading capacity, and in vitro release as a function of pH. Free and formulated curcumin were further investigated for cytotoxicity, apoptosis-induction and caspase-8, and 9 activation in chemosensitive HL-60 and its resistant sublines HL-60/Dox and HL-60/CDDP. Formulated curcumin was superior cytotoxic and apoptogenic agent vs. the free drug. The mechanistic assay demonstrated that the potent proapoptotic effects of pH-sensitive liposomal curcumin presumably mediated via recruitment of both extrinsic and intrinsic apoptotic pathways in both HL-60 and HL-60/CDDP cells

Geology and Geochemistry of the Shizitou Molybdenum Deposit, Jiangxi Province: Implications for Geodynamic Setting and Metallogenesis

The Shizitou molybdenum (Mo) deposit in Yongping, Jiangxi, is an important, recently discovered deposit in the eastern section of the Qin-Hang metallogenic belt. The Mo deposit is located in the outer contact zone between the porphyritic biotite granite and the Neoproterozoic migmatite, and present in the deep central part of the intrusion. Re-Os dating and S and Pb isotopic analysis have been conducted to assess the metallogenesis of the Shizitou Mo deposit. S, Pb and Re isotopes show that the ore-forming materials were derived from the porphyritic biotite granitic magma, which originated from the mixing of mantle and crust. Re-Os dating of molybdenite from the ores gives a model age from 156.9 +/- 2.2 to 158.5 +/- 2.4 Ma, with a weighted mean age of 158 +/- 1 Ma and an isochron age of 158.0 +/- 2.5 Ma. Geological and geochemical characteristics of the ore deposit and the related granitoids indicate that the Shizitou deposit is a Climax-type Mo deposit. Based on previous studies of the Qin-Hang metallogenic belt, two metallogenic events are believed to have occurred during 172-145 Ma and 137-132 Ma. These two metallogenic periods are consistent with the timing of two metallogenic peaks during the middle to late Jurassic and the Cretaceous in South China. These events represent responses to the partial backarc extension associated with the subduction of the Izanagi plate beneath the Eurasian continent and the rapid northeastward movement of the subducting Izanagi plate

Trace Element Geochemistry of Magnetite: Implications for Ore Genesis of the Huanggangliang Sn-Fe Deposit, Inner Mongolia, Northeastern China

The Huanggangliang deposit is a super-large Sn-Fe deposit in the Huanggangliang&ndash;Ganzhuermiao metallogenic belt in the southern section of the Great Hinggan Range. The Sn-Fe deposits mainly occur in the skarn contact zone and were formed via the interaction of biotite-bearing alkali feldspar granite with limestone strata of the Permian Dashizhai and Zhesi Formations. Based on the intersecting relations among the ore-bearing veins and the different types of mineral assemblages within these veins, the Sn-Fe mineralization could be divided into two periods and four stages: the skarn period, which includes the garnet&ndash;diopside&ndash;magnetite (T1) stage (stage 1) and epidote&ndash;idocrase&ndash;cassiterite&ndash;magnetite (T2) stage (stage 2); and the quartz&ndash;magnetite period, which can be divided into the quartz&ndash;cassiterite&ndash;magnetite (T3) stage (stage 3) and quartz&ndash;magnetite (T4) stage (stage 4). In this paper, we discuss the genesis of magnetite, controlling factors for magnetite compositions, and type of ore genesis based on petrographic studies and LA-ICP-MS analyses of trace elements in these four types of magnetite from the Huanggangliang Sn-Fe deposit. The results demonstrate that the four types of magnetite are generally depleted in Ti (0.002&ndash;3.030 wt %), Al (0.008&ndash;1.731 wt %), and Zr (&lt;1.610 ppm). In addition, the low Ni and Cr contents and relatively high and stable Fe contents in the four types of magnetite are indicative of hydrothermal genetic features. Compositions of the ore fluids and host rocks, formation of coexisting minerals, and other physical and chemical parameters (such as fO2) may have influenced the variable magnetite geochemistry in the different Huanggangliang ore types, with fluid compositions and fO2 probably playing the most important roles. The geological, petrographic, and geochemical characteristics of magnetite of the Huanggangliang Sn-Fe deposit lead us to conclude that the deposit is a skarn-type Sn-Fe deposit associated with Yanshanian medium-acidic magmatic activities

Degradation of toluene using UV/hydrogen peroxide process

Toluene in wastewater is volatile and difficult to degrade, and the longer it stays in the water, the higher is the risk. An advanced oxidation process (AOPs) has been used to degrade toluene rapidly and efficiently in wastewater by using ultraviolet light and hydrogen peroxide. Toluene in solution (initial concentration – 180 mg/dm3) with hydrogen peroxide (H2O2 dose – 2022 mg/dm3) was almost decomposed within 150 min. pH as well as the presence of various ions in waste water did not affect the degradation process. However, under strongly acidic conditions (pH less than 3), the chloride ions reduced the degradation efficiency of toluene. Based on the UV spectrophotometer and GC-MS analyses, the degradation pathways were observed: first, the methyl group was oxidized leading to the generation of benzoic acid, the benzene ring was subsequently opened by the action of hydroxyl radical, followed by the gradual decomposition of the intermediate products into small molecules such as water and carbon dioxide

Ore-Forming Processes at the Xiajinbao Gold Deposit in Eastern Hebei Province: Constraints from EPMA and LA-ICPMS Analysis

The Xiajinbao gold deposit is located at the northern margin of the North China Craton. Hydrothermal pyrites belonging to three stages were identified: Py1; Py2; and Py3. Geochemical study of these pyrites was conducted using electron probe microanalysis and laser ablation inductively coupled plasma mass spectrometry to investigate the distributions of minor and trace elements, constrain pyrite genesis, and to obtain an improved understanding of the ore-forming processes. Py1 and Py2 contain high concentrations of Au and are interpreted to have been deposited from fluids from a dominantly magmatic source. Py3 grains have the lowest Co/Ni ratios. All generations of pyrite were deposited by mixing of meteoric waters with magmatic-hydrothermal fluids. Boiling of early ore-forming fluids led to the precipitation of Py1 and gold. Decreasing fO2 in the ore-forming system resulted in the formation of Py2 and gold. Fluid mixing was the dominant controlling factor for the precipitation of Py3 together with small amounts of gold

Major and Trace Element Geochemistry of Pyrite and Pyrrhotite from Stratiform and Lamellar Orebodies: Implications for the Ore Genesis of the Dongguashan Copper (Gold) Deposit, Eastern China

The Dongguashan copper (gold) deposit in Anhui Province is one of the largest copper (gold) deposits in the Tongling ore district, which is the most important region in the Middle&ndash;Lower Yangtze River Metallogenic Belt, Eastern China. Stratiform and lamellar orebodies are the major deposit types. Pyrite and pyrrhotite from the stratiform deposit type (Py I, Po I) and lamellar deposit type (Py II, Po II) are investigated using Electron-probe Microanalyses (EPMA) and Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Py I, Py II, Po I and Po II have high contents of Cu, Co, Au and Se, low contents of As, Pb and Zn, with Co/Ni ratios of 0.50&minus;48.00, 4.00&minus;45.00, 1.55&minus;14.45 and 1.02&minus;1.36, respectively, most of which are greater than 1 and vary widely; these characteristics are consistent with those of pyrite with a magmatic&ndash;hydrothermal origin. The higher Au/Ag and Fe/(S + As) ratios of pyrite and crystallization temperatures (286&ndash;387 &deg;C) of hexagonal pyrrhotite indicate that the mineralization occurrs in environments with medium- to high-temperatures, high sulfur fugacity and medium-shallow depths. Therefore, we suggest that the Dongguashan copper (gold) deposit is a stratabound skarn-type ore deposit associated with magma intrusion activity during the Yanshanian Period