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Ewing’s sarcoma rarely arises from clavicle. Total claviculectomy is a generally accepted method of treatment with good functional outcome. We report a case of a 15 year male patient diagnosed with Ewing’s sarcoma clavicle treated with total claviculectomy. The purpose of our study is to evaluate the functional and oncological outcome after total resection of clavicle. This patient had full range of motion of the shoulder joint without any deficit. Thus, total claviculectomy can be considered as procedure in primary clavicular malignancy. Keywords: Total claviculectomy, Functional outcome, Ewing’s sarcoma.

Glioblastoma (GBM) is the most malignant form of brain tumor posing a major threat to cancer amelioration. Temozolomide (TMZ) resistance is one of the major hurdles towards GBM prognosis. Oxidative stress and ECM remodeling are the two important processes involved in gaining chemo-resistance. Here, we established NFE2L2, an important member of oxidative stress regulation elevated in resistant cells, to be playing a transcriptional regulatory role on MMP-2, an ECM remodeling marker. This link led us to further explore targeted molecules to inhibit NFE2L2, thus affecting MMP-2, an important member promoting chemo-resistance. Thus, diosgenin was proposed as a novel NFE2L2 inhibitor acting as an alternative strategy to prevent the high dose administration of TMZ. Combinatorial therapy of diosgenin and TMZ significantly reduced the dosage regimen of TMZ and also showed affectivity in hitherto TMZ resistant GBM cells. GBM cells underwent apoptosis and early cell cycle arrest with significant reduction in MMP-2 levels. Thus preclinical validation of molecular interaction between diosgenin and NFE2L2 down-regulating MMP-2, EMT markers and promoting apoptosis, offers rationale for new therapeutic horizons in the field of glioblastoma management.

The cyst wall ofEntamoeba histolytica,the causative agent of the amoebiasis, is a potential target for new drugs. The “Wattle and Daub” model of cyst wall formation ofEntamoeba invadenshad already been reported. In this study, we demonstrate in more detail the morphological stages of chitin wall formation inE. invadensusing fluorescent chitin-binding dyes and immunolocalization of the cyst wall proteins. Here, the expression and localization of chitin synthase and the importance of actin cytoskeleton dynamics at cellular level, during encystations have been demonstrated for the first time. Chitin deposition was found to be initiated on the cell surface mostly from one distinct point, though multipoint initiation was also observed sometimes. From these points, the wall grew outwards and gradually covered the entire cyst surface with time. The initiation of chitin deposition was guided by the localization of chitin synthase 1 on the plasma membrane. The gradual formation of the cyst wall follows the Wattle and daub model. The chitin deposition occurred on the foundation of Jacob lectin at the cell membrane, and the other cyst wall components, like chitinase, and Jessie were also found to be present in the growing incomplete walls. In contrary to the Wattle and daub model, Jessie was found to be expressed and localized in the growing wall at the early hours of encystations. During encystation, F-actin was reorganized into the cortical region within an hour encystation initiation and remained intact until the completion of the chitin wall. Disruption of cortical actin polymerization with 2, 3-Butanedione monoxime inhibited proper wall formation but produced wall-less cysts or cysts with defective chitin wall. Malformations of cyst-walls were mainly due to improper localization and activity of chitin synthases, which indicates the indispensability of cortical actin cytoskeleton for the proper cyst wall formation.Author SummaryEntamoebaparasites reach new hosts using the resistant cyst form, so preventing its formation can stop the spread of amoebiasis. The resistant nature of the cyst is due to the chitin wall, and thus identifying the critical steps of wall formation could provide targets for designing new drugs. Here we studied the morphological stages of the cyst wall formation by observing how the chitin and other cell wall components were deposited on the cell surface using fluorescent chitin-binding dyes and antibodies against cyst wall proteins. In most cases, the chitin wall was found to start from one distinct point from which it spread all over the cell surface, guided by chitin synthase. The composition of these incomplete walls was the same as a mature cyst wall indicating that the wall may be a result of extracellular self-assembly of its constituents from one starting point. We have also observed that F-actin polymerized in the cortex of encysting cells and its disruption resulted in wall-less cysts or cysts with aberrant walls showing the importance of actin cytoskeleton in proper chitin deposition.

Chitin, a homopolymer of β-(1,4) linked N-acetylglucosamine (GlcNAc), is a major component of cyst wall in the protozoan parasites Entamoeba histolytica (Eh) and Entamoeba invadens (Ei). The Entamoeba chitin synthase makes chitin at the vesicular membrane rather than the plasma membrane in fungi, even though the chemistry of chitin synthesis is most likely the same. However, the role of nucleotide sugar transporter(s) (NSTs) that are involved in chitin synthesis in Entamoeba are not yet established. In this study, we have identified the putative UDP-GlcNAc transporter (EiNst5) of Ei by BLASTP analysis using the amino acid sequence of EhNst3, the UDP-GlcNAc transporter of Eh. Heterologous expression of both EhNst3 and EiNst5 was found to complement the function of Yea4p (UDP-GlcNAc transporter of S. cerevisiae) in YEA4 null mutant and increased the cell wall chitin content. Like Yea4p in S. cerevisiae, Myc-epitope tagged EhNst3 and EiNst5 were localized to the endoplasmic reticulum in Δyea4 cells. The EiNST5 transcript was up-regulated during the in vitro encystation and oxidative stress in E. invadens. Similar up-regulation was also seen for EhNST3 under oxidative stress in E. histolytica. Down-regulation of EiNst5 expression using gene-specific dsRNA significantly reduced cyst formation during in vitro encystation in E. invadens. Our observations suggest for the first time the involvement of EhNst3 and EiNst5 in chitin synthesis and so in encystation of Entamoeba.

A robust reusable fluoride sensor comprised of a receptor in charge of the chemical recognition and a fluorophore responsible for signal recognition has been designed. Highly fluorescent carbon quantum dot (CD) and magnetically separable nickel ethylenediaminetetraacetic acid (EDTA) complex bound-silica coated magnetite nanoparticle (Fe3O4@SiO2–EDTA–Ni) have been used as fluorophore and fluoride ion receptor, respectively. The assay is based on the exchange reaction between the CD and F–, which persuades the binding of fluoride to magnetic receptor. This method is highly sensitive, fast, and selective for fluoride ion in aqueous solution. The linear response range of fluoride (R2 = 0.992) was found to be 1–20 μM with a minimum detection limit of 0.06 μM. Excellent magnetic property and superparamagnetic nature of the receptor are advantageous for the removal and well quantification of fluoride ion. The practical utility of the method is well tested with tap water. Because of high sensitivity, reusability,...

A novel biodegradable branched block copolymer was synthesized by the ring-opening polymerization of ethylene carbonate using pre-synthesized four-armed pentaerythretol poly(e-caprolactone) (PE-PCL) as a macro initiator. Folic acid was conjugated with the end-group of the block copolymer and self-assembled in water to form polymer micelles (PMs). The very low critical micelle concentration of the block copolymer suggests its potential application in advanced drug delivery systems. The PMs are spherical in shape and have an average size of 80 nm, which is suitable for the delivery of drugs. The hydrophobicity of pentaerythretol poly(e-caprolactone) and its branched structure can accommodate high amounts of doxorubicin. Compared with a blank sample, PMs containing encapsulated doxorubicin show a much higher cytotoxicity towards HeLa cells. A high rate of release of doxorubicin in vitro at pH 5.0 shows that the system is responsive to pH. Confocal laser scanning microscopy showed that the doxorubicin-loaded PMs were internalized into the HeLa cells.

Judicious combination of fluorescence and magnetic properties along with ample drug loading capacity and control release property remains a key challenge in the design of nanotheranostic agents. This paper reports the synthesis of highly hydrophilic optically traceable mesoporous carbon nanospheres which can sustain payloads of the anticancer drug doxorubicin and T2 contrast agent such as cobalt ferrite nanoparticles. The luminescent magnetic hybrid system has been prepared on a mesoporous silica template using a resorcinol-formaldehyde precursor. The mesoporous matrix shows controlled release of the aromatic drug doxorubicin due to disruption of supramolecular π-π interaction at acidic pH. The particles show MR contrast behavior by affecting the proton relaxation with transverse relaxivity (r2) 380 mM(-1) S(-1). The multicolored emission and upconversion luminescence property of our sample are advantageous in bioimaging. In vitro cell experiments shows that the hybrid nanoparticles are endocyted by the tumor cells through passive targeting. The pH-responsive release of doxorubicin presents chemotherapeutic inhibition of cell growth through induction of apoptosis.

A robust reusable fluoride sensor comprised of a receptor in charge of the chemical recognition and a fluorophore responsible for signal recognition has been designed. Highly fluorescent carbon quantum dot (CD) and magnetically separable nickel ethylenediaminetetraacetic acid (EDTA) complex bound-silica coated magnetite nanoparticle (Fe3O4@SiO2-EDTA-Ni) have been used as fluorophore and fluoride ion receptor, respectively. The assay is based on the exchange reaction between the CD and F(-), which persuades the binding of fluoride to magnetic receptor. This method is highly sensitive, fast, and selective for fluoride ion in aqueous solution. The linear response range of fluoride (R(2) = 0.992) was found to be 1-20 μM with a minimum detection limit of 0.06 μM. Excellent magnetic property and superparamagnetic nature of the receptor are advantageous for the removal and well quantification of fluoride ion. The practical utility of the method is well tested with tap water. Because of high sensitivity, reusability, effectivity, and biocompatibility, it exhibits great promise as a fluorescent probe for intracellular detection of fluoride.