Radiochemical Feasibility of Mixing of Tc-MAA and Y-Microspheres with Omnipaque Contrast.

Yttrium-90 (Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (Tc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution.

The repertoire of testicular extracellular vesicle cargoes and their involvement in inter-compartmental communication associated with spermatogenesis.

Background: Spermatogenesis is regulated by a complex network of intercellular communication processes. Extracellular vesicles (EVs) are one of the important mediators in intercellular communication. Previous reports have demonstrated the involvement of EVs from the epididymis and prostate in sperm maturation and function.

Patient-Derived Nasopharyngeal Cancer Organoids for Disease Modeling and Radiation Dose Optimization.

Effective radiation treatment (RT) for recurrent nasopharyngeal cancers (NPC), featuring an intrinsic hypoxic sub-volume, remains a clinical challenge. Lack of disease-specific models of NPC, together with difficulties in establishing patient derived xenograft (PDX) models, have further hindered development of personalized therapeutic options. Herein, we established two NPC organoid lines from recurrent NPC PDX models and further characterized and compared these models with original patient tumors using RNA sequencing analysis.

Inhibition of Sar1b, the Gene Implicated in Chylomicron Retention Disease, Impairs Migration and Morphogenesis of Developing Cortical Neurons.

Chylomicron Retention Disease (CMRD) is a rare inherited lipid malabsorption syndrome that exhibits a recessive hypocholesterolemia in infants. CMRD has been associated with genetic mutations of SAR1B-a member of the Arf GTPase family involved in the secretory pathway from the endoplasmic reticulum to the Golgi. CMRD patients suffer from multiple neurological deficits, the etiologies of which remain unclear.

Distinct Roles of TRAPPC8 and TRAPPC12 in Ciliogenesis via Their Interactions With OFD1.

The transport protein particle (TRAPP) complex was initially identified as a tethering factor for COPII vesicle. Subsequently, three forms (TRAPPI, II, and III) have been found and TRAPPIII has been reported to serve as a regulator in autophagy. This study investigates a new role of mammalian TRAPPIII in ciliogenesis.

The Golgin Protein Giantin Regulates Interconnections Between Golgi Stacks.

Golgins are a family of Golgi-localized long coiled-coil proteins. The major golgin function is thought to be the tethering of vesicles, membranes, and cytoskeletal elements to the Golgi. We previously showed that knockdown of one of the longest golgins, Giantin, altered the glycosylation patterns of cell surfaces and the kinetics of cargo transport, suggesting that Giantin maintains correct glycosylation through slowing down transport within the Golgi.

Alterations in branched-chain amino acid kinetics in nonobese but insulin-resistant Asian men.

Background: Branched-chain amino acids (BCAAs) are elevated in the insulin-resistant (IR) state. The reasons for this increase remain unclear, but it may be related to abnormalities in BCAA metabolism and free fatty acid (FFA) metabolism.

Objective: In this study, we quantified BCAA and FFA kinetics of IR and insulin-sensitive (IS) nonobese Asian men with the use of stable-isotope tracers.

Controlling injectability and in vivo stability of thermogelling copolymers for delivery of yttrium-90 through intra-tumoral injection for potential brachytherapy.

Intra-tumoral injection of radiopharmaceuticals such as yttrium-90 (Y) or phosphorus-32 (P) is an important route for brachytherapy in unresectable solid tumors such as locally advanced hepatocellular carcinoma. However, the injected radiopharmaceuticals can potentially leak out from the tumor site due to high intra-tumoral pressure. In this study, we demonstrated the use of thermogelling copolymers that can be injected into tumor and subsequently solidify as hydrogels within the tumor that can potentially overcome the above problem.

Correction: A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C.

[This corrects the article DOI: 10.18632/oncotarget.19960.

Clostridium difficile toxin B induces autophagic cell death in colonocytes.

Toxin B (TcdB) is a major pathogenic factor of Clostridum difficile. However, the mechanism by which TcdB exerts its cytotoxic action in host cells is still not completely known. Herein, we report for the first time that TcdB induced autophagic cell death in cultured human colonocytes.

Reduced lysosomal clearance of autophagosomes promotes survival and colonization of Helicobacter pylori.

Evasion of autophagy is key for intracellular survival of bacteria in host cells, but its involvement in persistent infection by Helicobacter pylori, a bacterium identified to invade gastric epithelial cells, remains obscure. The aim of this study was to functionally characterize the role of autophagy in H. pylori infection.

Retinoic acid promotes stem cell differentiation and embryonic development by transcriptionally activating CFTR.

Retinoic acid (RA) plays a pivotal role in many cellular processes; however, the signaling mechanisms mediating the effect of RA are not fully understood. Here, we show that RA transcriptionally upregulates cystic fibrosis transmembrane conductance regulator (Cftr) by promoting the direct binding of its receptor RARα to Cftr promoter in mouse spermatogonia and embryonic stem (ES) cells. The RA/CFTR pathway is involved in the differentiation of spermatogonia and organogenesis during the embryo development of Xenopus laevis.

A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C.

Lipid droplet (LD) homeostasis involves activities of various RAB small GTPases. Recently, we found RAB40C was one of the RAB proteins regulating LD homeostasis. RAB40C contains a unique SOCS domain that is required for clustering of LDs.

Push-pull type meso-ester substituted BODIPY near-infrared dyes as contrast agents for photoacoustic imaging.

A series of push-pull type meso-ester substituted BODIPY dyes 1-4 with intense near-infrared absorption, largely enhanced photoacoustic (PA) activity and excellent photo-stability were synthesized. The impact of the electronic structure on the PA activity was also discussed. Moreover, the in vitro and in vivo PA imaging were investigated, which suggested a passive targeting capacity in the tumor site.

ULK1 phosphorylates Sec23A and mediates autophagy-induced inhibition of ER-to-Golgi traffic.

Background: Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway.

Mammalian TRAPPIII Complex positively modulates the recruitment of Sec13/31 onto COPII vesicles.

The Transport protein particle (TRAPP) complex is a tethering factor for COPII vesicle. Of three forms of TRAPP (TRAPPI, II and III) complexes identified so far, TRAPPIII has been largely considered to play a role in autophagy. While depletion of TRAPPIII specific subunits caused defects in the early secretory pathway and TRAPPIII might interact with components of the COPII vesicle coat, its exact role remains to be determined.

COPI-TRAPPII activates Rab18 and regulates its lipid droplet association.

The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1.

Noninvasive in vivo multispectral optoacoustic imaging of apoptosis in triple negative breast cancer using indocyanine green conjugated phosphatidylserine monoclonal antibody.

Noninvasive and nonradioactive imaging modality to track and image apoptosis during chemotherapy of triple negative breast cancer is much needed for an effective treatment plan. Phosphatidylserine (PS) is a biomarker transiently exposed on the outer surface of the cells during apoptosis. Its externalization occurs within a few hours of an apoptotic stimulus by a chemotherapy drug and leads to presentation of millions of phospholipid molecules per apoptotic cell on the cell surface.

Naphthalene-fused BODIPY near-infrared dye as a stable contrast agent for in vivo photoacoustic imaging.

Photoacoustic imaging (PAI) has emerged as an advantageous modality with high resolution and deep tissue penetration. However, its application is limited by the lack of available contrast agents. In this work, we report the synthesis of a naphthalene fused BODIPY dimer Na-BD, and the impact of the electronic structure on the oxidative cyclo-dehydrogenation process was systematically studied.

Rab proteins as regulators of lipid droplet formation and lipolysis.

Lipid droplets (LDs) are highly dynamic organelles that not only store neutral lipids but also are involved in multiple cellular processes. Dysregulation of lipogenesis or lipolysis greatly contributes to the pathogenesis of several human diseases, including obesity, diabetes, and fatty liver disease. Rab proteins have been found to be associated with LDs in proteomic studies and are also known to extensively regulate intracellular membrane traffic, suggesting that LDs actively communicate with other membrane compartments to maintain energy homeostasis.

Hepatitis C virus NS5A protein cooperates with phosphatidylinositol 4-kinase IIIα to induce mitochondrial fragmentation.

Hepatitis C virus (HCV) has long been observed to take advantage of the host mitochondria to support viral replication and assembly. The HCV core protein has been implicated to fragment host mitochondria. In this report, we have discovered that the non-structural protein 5A (NS5A) plays an instructive role in attaching ER with mitochondria, causing mitochondrial fragmentation.

A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model.

Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives.

Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging.

Autophagy Mediates HBx-Induced Nuclear Factor-κB Activation and Release of IL-6, IL-8, and CXCL2 in Hepatocytes.

Hepatitis B virus (HBV) and one of its encoded proteins, HBV X protein (HBx), have been shown to induce autophagy in hepatoma cells. Substantial evidence indicates that autophagy is a potent suppressor of inflammation. However, sporadic reports suggest that autophagy could promote pro-inflammatory cytokine expression and inflammation in some biological contexts.

Bet3 participates in autophagy through GTPase Ypt1 in Saccharomyces cerevisiae.

Three TRAPP (transport protein particle) complexes have been identified in Saccharomyces cerevisiae. GTPases Ypt1 and Ypt31/32 suppress autophagic defects in the mutants of TRAPPIII-specific subunit (Trs85) and TRAPPII-specific subunits (Trs130 and Trs120), respectively. However, the roles of the common TRAPP subunits (which also form the TRAPPI complex) in autophagy and their relationship to Rab GTPases in autophagy remain unclear.