Case report: Diagnosis and surgical treatment of delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax in a small dog.

An 8-year-old castrated male teddy bear dog presented to our clinic with a persistent cough. The sick dog suffered from vehicular trauma 6 months prior to the visit and had imaging and exploratory laparotomy. Imaging and exploratory laparotomy at the time showed no significant damage. We performed contrast radiography (barium gavage) on the sick dog. Based on the results of a complete contrast radiography (barium gavage), tubular shadows in the thoracic cavity were identified as the small intestine and cecum, and delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax was confirmed with radiographs. Accordingly, the sick dog underwent general anesthesia, manual ventilation and diaphragmatic herniorrhaphy by standard ventral midline abdominal approach. Postoperatively, the dog was given analgesia and antibacterial treatment, and the liver biochemical indexes were monitored to prevent endotoxin. Postoperative radiographs revealed clear contours of thoracic and abdominal organs. The dog moved, ate, and urinated normally within 10 days of the surgery. This case provides a reference for a complete barium meal imaging procedure that clearly shows the position of the organs in the thoracoabdominal cavity after the occurrence of a delayed traumatic diaphragmatic hernia. This paper provides a practical reference for the diagnosis of delayed traumatic diaphragmatic hernia with hepatothorax and enterothorax.

The antagonism mechanism of astilbin against cadmium-induced injury in chicken lungs via Treg/Th1 balance signaling pathway.

The purpose of this study was to investigate the effect of Treg/Th1 imbalance in cadmium-induced lung injury and the potential protective effect of astilbin against cadmium-induced lung injury in chicken. Cadmium exposure significantly decreased T-AOC and GSH-Px levels and SOD activity in the chicken lung tissues. In contrast, it significantly increased the MDA and NO levels. These results indicate that cadmium triggers oxidative stress in lungs. Histopathological analysis revealed that cadmium exposure further induced infiltration of lymphocytes in the chicken lungs, indicating that cadmium causes pulmonary damage. Further analysis revealed that cadmium decreased the expression of IL-4 and IL-10 but increased those of IL-17, Foxp3, TNF-α, and TGF-ß, indicating that the exposure of cadmium induced the imbalance of Treg/Th1. Moreover, cadmium adversely affected chicken lung function by activating the NF-kB pathway and inducing expression of genes downstream to these pathways (COX-2, iNOS), associated with inflammatory injury in the lung tissue. Astilbin reduced cadmium-induced oxidative stress and inflammation in the lungs by increasing antioxidant enzyme activities and restoring Treg/Th1 balance. In conclusion, our results suggest that astilbin treatment alleviated the effects of cadmium-mediated lung injury in chickens by restoring the Treg/Th1 balance.

Tumor-associated macrophage-derived exosomal miR21-5p promotes tumor angiogenesis by regulating YAP1/HIF-1α axis in head and neck squamous cell carcinoma.

Extracellular vesicles (EVs) have recently received increasing attention as essential mediators of communication between tumor cells and their microenvironments. Tumor-associated macrophages (TAMs) play a proangiogenic role in various tumors, especially head and neck squamous cell carcinoma (HNSCC), and angiogenesis is closely related to tumor growth and metastasis. This research focused on exploring the mechanisms by which EVs derived from TAMs modulate tumor angiogenesis in HNSCC. Our results indicated that TAMs infiltration correlated positively with microvascular density in HNSCC. Then we collected and identified EVs from TAMs. In the microfluidic chip, TAMs derived EVs significantly enhanced the angiogenic potential of pHUVECs and successfully induced the formation of perfusable blood vessels. qPCR and immunofluorescence analyses revealed that EVs from TAMs transferred miR-21-5p to endothelial cells (ECs). And targeting miR-21-5p of TAMs could effectively inhibit TAM-EVs induced angiogenesis. Western blot and tube formation assays showed that miR-21-5p from TAM-EVs downregulated LATS1 and VHL levels but upregulated YAP1 and HIF-1α levels, and the inhibitors of YAP1 and HIF-1α could both reduce the miR-21-5p enhanced angiogenesis in HUVECs. The in vivo experiments further proved that miR-21-5p carried by TAM-EVs promoted the process of tumor angiogenesis via YAP1/HIF-1α axis in HNSCC. Conclusively, TAM-derived EVs transferred miR-21-5p to ECs to target the mRNA of LATS1 and VHL, which inhibited YAP1 phosphorylation and subsequently enhanced YAP1-mediated HIF-1α transcription and reduced VHL-mediated HIF-1α ubiquitination, contributing to angiogenesis in HNSCC. These findings present a novel regulatory mechanism of tumor angiogenesis, and miR-21-5p/YAP1/HIF-1α might be a potential therapeutic target for HNSCC.

Fluorine-mediated synthesis of anisotropic iron oxide nanostructures for efficient T2-weighted magnetic resonance imaging.

Herein, we developed a novel strategy for the shape-controlled synthesis of iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent and dopant. The selective adsorption of fluoride ions onto the specified crystal planes of iron oxide nanocrystals leads to the formation of octapod nanoparticles (ONPs) and cubic nanocrystal clusters (CNCs). Both ONPs and CNCs present high r2 values (526.5 and 462.2 mM-1 s-1, respectively) due to the synergistic effect of a larger effective radius, clustering and fluorine doping. The in vivo MRI results show significant enhancement in T2-weighted images of the liver after the intravenous injection of ONPs and CNCs, suggesting their great potential as efficient T2-weighted MRI contrast agents. This new approach of achieving anisotropic fluorine-doped iron oxide nanostructures with high r2 relaxivity provides an alternative strategy for the development of highly sensitive T2 contrast agents for MRI.

Activatable NIR-II Plasmonic Nanotheranostics for Efficient Photoacoustic Imaging and Photothermal Cancer Therapy.

Precise manipulation of optical properties through the structure-evolution of plasmonic nanoparticles is of great interest in biomedical fields including bioimaging and phototherapy. However, previous success has been limited to fixed assembled structures or visible-NIR-I absorption. Here, an activatable NIR-II plasmonic theranostics system based on silica-encapsulated self-assembled gold nanochains (AuNCs@SiO2 ) for accurate tumor diagnosis and effective treatment is reported. This transformable chain structure breaks through the traditional molecular imaging window, whose absorption can be redshifted from the visible to the NIR-II region owing to the fusion between adjacent gold nanoparticles in the restricted local space of AuNCs@SiO2 triggered by the high H2 O2 level in the tumor microenvironment (TME), leading to the generation of a new string-like structure with strong NIR-II absorption, which is further confirmed by finite-difference-time-domain (FDTD) simulation. With the TME-activated characteristics, AuNCs@SiO2 exhibits excellent properties for photoacoustic imaging and a high photothermal conversion efficiency of 82.2% at 1064 nm leading to severe cell death and remarkable tumor growth inhibition in vivo. These prominent intelligent TME-responsive features of AuNCs@SiO2 may open up a new avenue to explore optical regulated nano-platform for intelligent, accurate, and noninvasive theranostics in NIR-II window.

Synthesis Of PEG-Coated, Ultrasmall, Manganese-Doped Iron Oxide Nanoparticles With High Relaxivity For T1/T2 Dual-Contrast Magnetic Resonance Imaging.

BACKGROUND: Beyond magnetic resonance imaging (MRI), which has been widely used clinically, molecular MRI (mMRI) can further provide qualitative and quantitative information at the cellular and molecular levels. However, the diagnostic accuracy may not be satisfactory via single-contrast mMRI due to some interferences in vivo. T1/T2 dual-contrast MRI using the same contrast agent (CA) could significantly improve the detection accuracy. Therefore, in this study, we fabricated poly(ethylene glycol) (PEG)-coated, manganese-doped iron oxide nanocomposites (Mn-IONPs@PEG) as T1/T2 dual-contrast CA, and evaluated its feasibility of T1/T2 dual-contrast MRI in vitro and in vivo. METHODS: Mn-IONPs were prepared by the thermal decomposition of iron-eruciate and manganese-oleate complexes and were coated with 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-(methoxy[polyethylene glycol]-2000) (DSPE-PEG 2000). The physicochemical properties and cytotoxicity of the Mn-IONPs were fully characterized, followed by MRI in vitro and in vivo. RESULTS: Ultrasmall 3 nm-sized nanoparticles were successfully prepared and were identified using transmission electron microscopy (TEM), high-resolution TEM, and X-ray diffraction. After coating with DSPE-PEG, the Mn-IONPs@PEG displayed excellent hydrophilicity and good biocompatibility. Due to the manganese-doping and PEG coating, the Mn-IONPs@PEG showed good relaxivity in vitro. Especially, the Mn-IONPs@PEG coated with DSPE-PEG following a mass ratio to Mn-IONPs of 1:20 showed harmonious longitudinal relaxivity (r 1 = 7.1 mM-1s-1) and transversal relaxivity (r 2 = 120.9 mM-1s-1), making it a better candidate for T1/T2 dual-contrast mMRI. After administrated via a caudal vein, the Mn-IONPs@PEG can induce significant enhancement in both T1-weighted and T2-weighted MR images and the time at 10 mins after injection was regarded as a suitable time for imaging because both the T1 and T2 enhancement were optimum at that time. CONCLUSION: The obtained Mn-IONPs@PEG exhibited good r 1 and r 2 and was a reasonable candidate for T1/T2 dual-contrast mMRI.

Migration of Iron Oxide Nanoparticle through a Silica Shell by the Redox-Buffering Effect.

This study demonstrates that mineral redox buffer, an important concept in geology, can be used to manipulate the migration of nanoparticles and produce nanostructures of unexpected morphologies. Using a silica shell as a redox buffer, we show that iron oxide nanoparticles can be relocated from inside to the outer surface of the silica shell. The migration of iron oxide through silica was initiated by manipulation of the oxygen fugacity conditions at an elevated temperature. During the treatment, iron oxide was absorbed and then separated from the silica shell by the formation and then decomposition of iron silicate (Fe2SiO4). Tuning the relative dimensions of the iron oxide core and silica shell allows control of the shape of the iron oxide-silica composite structures. It is believed that the discovery of the nanoscale redox buffering effect can be extended to control the morphological configuration of other multivalent metal oxide nanocomposite structures by this particular type of template synthesis through manipulation of the chemical-transport properties of nanoscale templates.

High-yield halide-free synthesis of biocompatible Au nanoplates.

We communicate an unconventional synthesis of Au nanoplates with high yield and excellent reproducibility through polyvinylpyrrolidone (PVP)-assisted H2O2 reduction. Unlike the ones prepared using halide-based surfactants, the PVP-capped Au nanoplates are found to afford fairly easy bio-functionalization, suggesting a vastly expanded spectrum of applications in bio-related fields.

Sumoylation of vimentin354 is associated with PIAS3 inhibition of glioma cell migration.

The invasive phenotype of glioblastoma multiforme (GBM) is a hallmark of malignant process, yet the molecular mechanisms that dictate this locally invasive behavior remain poorly understood. Over-expression of PIAS3 effectively changes cell shape and inhibits GBM cell migration. We focused on the molecular target(s) of PIAS3 stimulated sumoylation, which play an important role in the inhibition of GBM cell motility. Here we report, through the immunoprecipitation with SUMO1 antibody, followed by proteomic analysis, the identification of vimentin (vimentin354), a nuclear component in GBM cells, as the main target of sumoylation promoted by PIAS3.

Detection of mononucleotide repeat sequence alterations in a large background of normal DNA for screening high-frequency microsatellite instability cancers.

PURPOSE: Mutations in mononucleotide repeat sequence (MRS) are good indicators of high-frequency microsatellite instability (MSI-H) cancers, but it has been a challenge to detect such mutations in a large background of wild-type DNA; as in this setting, PCR errors often generate false positive mutant alleles. In this study, we developed a general strategy, referred to as probe clamping primer extension-PCR (PCPE-PCR), to detect MRS alterations in a large background of wild-type DNA. EXPERIMENTAL DESIGN: In PCPE-PCR, genomic DNA is first subjected to PCPE, in which mutant single-strand DNA molecules are preferentially produced. Next, genomic DNA is removed to enrich for the mutant DNA fraction. Thereafter, PCR is carried out using the remaining single-strand DNA molecules as templates. Finally, the PCR products are analyzed to reveal the MSI-H status. In this study, the sensitivity of this new method was first examined by spiking mutant DNA into wild-type DNA at specific ratios followed by studying whether this method is applicable to fecal DNA testing. RESULTS: We showed that PCPE-PCR could detect both mutated BAT26 and transforming growth factor-beta-RII (A)10 markers in the presence of 500-fold excess of normal DNA and that as few as three copies of mutated DNA could be detected. In addition, we showed that this technology could detect MSI-H colorectal cancer by fecal DNA analysis. CONCLUSION: PCPE-PCR is sensitive. In addition, PCPE-PCR is simple and amendable to a cost-effective and high-throughput screening operation. This technology may be applicable to noninvasive screening of MSI-H cancer.

Clavulanic acid inactivation of SHV-1 and the inhibitor-resistant S130G SHV-1 beta-lactamase. Insights into the mechanism of inhibition.

Clavulanic acid is a potent mechanism-based inhibitor of TEM-1 and SHV-1beta-lactamases, enzymes that confer resistance to beta-lactams in many gram-negative pathogens. This compound has enjoyed widespread clinical use as part of beta-lactam beta-lactamase inhibitor therapy directed against penicillin-resistant pathogens. Unfortunately, the emergence of clavulanic acid-resistant variants of TEM-1 and SHV-1 beta-lactamase significantly compromise the efficacy of this combination. A single amino acid change at Ambler position Ser130 (Ser --> Gly) results in resistance to inactivation by clavulanate in the SHV-1 and TEM-1beta-lactamases. Herein, we investigated the inactivation of SHV-1 and the inhibitor-resistant S130G variant beta-lactamases by clavulanate. Using liquid chromatography electrospray ionization mass spectrometry, we detected multiple modified proteins when SHV-1 beta-lactamase is inactivated by clavulanate. Matrix-assisted laser desorption ionization-time of flight mass spectrometry was used to study tryptic digests of SHV-1 and S130Gbeta-lactamases (+/- inactivation with clavulanate) and identified peptides modified at the active site Ser70. Ultraviolet (UV) difference spectral studies comparing SHV-1 and S130Gbeta-lactamases inactivated by clavulanate showed that the formation of reaction intermediates with absorption maxima at 227 and 280 nm are diminished and delayed when S130Gbeta-lactamase is inactivated. We conclude that the clavulanic acid inhibition of the S130G beta-lactamase must follow a branch of the normal inactivation pathway. These findings highlight the importance of understanding the intermediates formed in the inactivation process of inhibitor-resistant beta-lactamases and suggest how strategic chemical design can lead to novel ways to inhibit beta-lactamases.