Use of a Multilayered Stent for the Treatment of Hepatic Artery Pseudoaneurysm After Liver Transplantation
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Highlights: • The expression pattern of CMTM7 and SOX10 are down-regulated in GC. • SOX10 is a transcriptional regulator of CMTM7 in GC. • SOX10 mediate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7. Numerous studies have shown that CMTM family members have a variety of important roles in the occurrence and progression of cancer. CMTM7 has also been reported to be down-regulated in some digestive system tumors, but the expression patterns and pathological role of CMTM7 in gastric cancer remains unclear. In this study, we found that both CMTM7 and SOX10 were significantly down-regulated in gastric cancer tissues compared with paracancerous tissues, and the expression pattern of CMTM7 and SOX10 were strongly correlated (r = 0.6455, p < 0.001). Further, through bioinformatics technology and luciferase assay, we identify that SOX10 can be a transcriptional regulator of CMTM7 to mediate the expression of CMTM7 in gastric cancer. In addition, we found silencing the expression of CMTM7 can increase the proliferation and tumorigenesis of gastric cancer cells in vivo and in vitro. More interestingly, overexpression of SOX10 in cell lines stably silencing CMTM7 expression significantly inhibited the proliferation and tumor growth of gastric cancer. Therefore, our results demonstrate that CMTM7 as a tumor suppressor is down-regulated in gastric cancer, and SOX10 can regulate the proliferation and tumor formation of gastric cancer by regulating the expression of CMTM7.
Purpose: To address the characteristics and the causative factors of radiation-induced cranial nerve palsy (CNP) in nasopharyngeal carcinoma (NPC) patients with an extensive period of followed-up. Patients and Methods: A total of 317 consecutive and nonselected patients treated with definitive external-beam radiotherapy between November 1962 and February 1995 participated in this study. The median doses to the nasopharynx and upper neck were 71 Gy (range, 55-86 Gy) and 61 Gy (range, 34-72 Gy), respectively. Conventional fractionation was used in 287 patients (90.5%). Forty-five patients (14.2%) received chemotherapy. Results: The median follow-up was 11.4 years (range, 5.1-38.0 years). Ninety-eight patients (30.9%) developed CNP, with a median latent period of 7.6 years (range, 0.3-34 years). Patients had a higher rate of CNP (81 cases, 25.5%) in lower-group cranial nerves compared with upper group (44 cases, 13.9%) ({chi}{sup 2} = 34.444, p < 0.001). Fifty-nine cases experienced CNP in more than one cranial nerve. Twenty-two of 27 cases (68.8%) of intragroup CNP and 11 of 32 cases (40.7%) of intergroup CNP occurred synchronously ({chi}{sup 2} = 4.661, p = 0.031). The cumulative incidences of CNP were 10.4%, 22.4%, 35.5%, and 44.5% at 5, 10, 15, and 20 years, respectively. Multivariate analyses revealed that CNP at diagnosis, chemotherapy, total radiation dose to the nasopharynx, and upper neck fibrosis were independent risk factors for developing radiation-induced CNP. Conclusion: Radiation-induced fibrosis may play an important role in radiation-induced CNP. The incidence of CNP after definitive radiotherapy for NPC remains high after long-term follow-up and is dose and fractionation dependent.
Complex glycans that evade our digestive system are major nutrients that feed the human gut microbiota (HGM). The prevalence of Bacteroidetes in the HGM of populations worldwide is engendered by the evolution of polysaccharide utilization loci (PULs), which encode concerted protein systems to utilize the myriad complex glycans in our diets. Despite their crucial roles in glycan recognition and transport, cell-surface glycan-binding proteins (SGBPs) remained understudied cogs in the PUL machinery. Here, we report the structural and biochemical characterization of a suite of SGBP-A and SGBP-B structures from three syntenic β(1,3)-glucan utilization loci (1,3GULs) from Bacteroides thetaiotaomicron (Bt), Bacteroides uniformis (Bu), and B. fluxus (Bf), which have varying specificities for distinct β-glucans. Ligand complexes provide definitive insight into β(1,3)-glucan selectivity in the HGM, including structural features enabling dual β(1,3)-glucan/mixed-linkage β(1,3)/β(1,4)-glucan-binding capability in some orthologs. The tertiary structural conservation of SusD-like SGBPs-A is juxtaposed with the diverse architectures and binding modes of the SGBPs-B. Specifically, the structures of the trimodular BtSGBP-B and BuSGBP-B revealed a tandem repeat of carbohydrate-binding module-like domains connected by long linkers. In contrast, BfSGBP-B comprises a bimodular architecture with a distinct β-barrel domain at the C terminus that bears a shallow binding canyon. The molecular insights obtained here contribute to our fundamental understanding of HGM function, which in turn may inform tailored microbial intervention therapies.
When treating pancreatic cancer using standard (ST) 3D conformal radiotherapy (3D-CRT) beam arrangements, the kidneys often receive a higher dose than their probable tolerance limit. Our aim was to elaborate a new planning method that-similarly to IMRT-effectively spares the kidneys without compromising the target coverage. Conformal kidneys sparing (CONKISS) 5-field, noncoplanar plans were compared with ST plans for 23 consecutive patients retrospectively. Optimal beam arrangements were used consisting of a left- and right-wedged beam-pair and an anteroposterior beam inclined in the caudal direction. The wedge direction determination (WEDDE) algorithm was developed to adjust the adequate direction of wedges. The aimed organs at risk (OARs) mean dose limits were: kidney <12 Gy, liver <25 Gy, small bowels <30 Gy, and spinal cord maximum <45 Gy. Conformity and homogeneity indexes with z-test were used to evaluate and compare the different planning approaches. The mean dose to the kidneys decreased significantly (p < 0.05): left kidney 7.7 vs. 10.7 Gy, right kidney 9.1 vs. 11.7 Gy. Meanwhile the mean dose to the liver increased significantly (18.1 vs. 15.0 Gy). The changes in the conformity, homogeneity, and in the doses to other OARs were not significant. The CONKISS method balances the load among the OARs and significantly reduces the dose to the kidneys, without any significant change in the conformity and homogeneity. Using 3D-CRT the CONKISS method can be a smart alternative to IMRT to enhance the possibility of dose escalation.
Earlier studies indicated that transgenic (tg) mice engineered to express prion protein (PrP) lacking the glycophosphatidylinositol (GPI{sup -/-}) membrane anchor formed abnormal proteinase-resistant prion (PrPsc) amyloid deposits in their brains and hearts when infected with the RML strain of murine scrapie. In contrast, RML scrapie infection of normal mice with a GPI-anchored PrP did not deposit amyloid with PrPsc in the brain or the heart. Here we report that scrapie-infected GPI{sup -/-} PrP tg mice also deposit PrP and transmissible infectious material in the gut, kidneys, and islets of Langerhans. Similar to previously reported amyloid deposits in the brain and heart, amyloid deposits were found in the gut; however, no amyloid deposited in the islets. By high-resolution electron microscopy, we show PrP is located primarily in {alpha} cells and also {beta} cells. Islets contain abundant insulin and there is no abnormality in glucose metabolism in infected GPI{sup -/-} PrP tg mice.
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N-acetylated α-linked acidic dipeptidase-like protein (NAALADase L), encoded by the NAALADL1 gene, is a close homolog of glutamate carboxypeptidase II, a metallopeptidase that has been intensively studied as a target for imaging and therapy of solid malignancies and neuropathologies. However, neither the physiological functions nor structural features of NAALADase L are known at present. In this paper, we report a thorough characterization of the protein product of the human NAALADL1 gene, including heterologous overexpression and purification, structural and biochemical characterization, and analysis of its expression profile. By solving the NAALADase L x-ray structure, we provide the first experimental evidence that it is a zinc-dependent metallopeptidase with a catalytic mechanism similar to that of glutamate carboxypeptidase II yet distinct substrate specificity. A proteome-based assay revealed that the NAALADL1 gene product possesses previously unrecognized aminopeptidase activity but no carboxy- or endopeptidase activity. These findings were corroborated by site-directed mutagenesis and identification of bestatin as a potent inhibitor of the enzyme. Analysis of NAALADL1 gene expression at both the mRNA and protein levels revealed the small intestine as the major site of protein expression and points toward extensive alternative splicing of the NAALADL1 gene transcript. Taken together, our data imply that the NAALADL1 gene product's primary physiological function is associated with the final stages of protein/peptide digestion and absorption in the human digestive system. Finally, based on these results, we suggest a new name for this enzyme: human ileal aminopeptidase (HILAP).
Abnormalities in zinc homeostasis are indicated in many human diseases, including Alzheimer disease (AD). 63 Zn-zinc citrate was developed as a positron emission tomography (PET) imaging probe of zinc transport and used in a first-in-human study in 6 healthy elderly individuals and 6 patients with clinically confirmed AD. A dynamic PET imaging of the brain was performed for 30 minutes following intravenous administration of 63 Zn-zinc citrate (~330 MBq). Subsequently, body PET images were acquired. Urine and venous blood were analyzed to give information on urinary excretion and pharmacokinetics. Regional cerebral 63 Zn clearances were compared with 11 C-Pittsburgh Compound B ( 11 C-PiB) and 18 F-fluorodeoxyglucose ( 18 F-FDG) imaging data. 63 Zn-zinc citrate was well tolerated in human participants with no adverse events monitored. Tissues of highest uptake were liver, pancreas, and kidney, with moderate uptake being seen in intestines, prostate (in males), thyroid, spleen, stomach, pituitary, and salivary glands. Moderate brain uptake was observed, and regional dependencies were observed in 63 Zn clearance kinetics in relationship with regions of high amyloid-β plaque burden ( 11 C-PiB) and 18 F-FDG hypometabolism. In conclusion, zinc transport was successfully imaged in human participants using the PET probe 63 Zn-zinc citrate. Primary sites of uptake in the digestive system accent the role of zinc in gastrointestinal function. Preliminary information on zinc kinetics in patients with AD evidenced regional differences in clearance rates in correspondence with regional amyloid-β pathology, warranting further imaging studies of zinc homeostasis in patients with AD.
In this paper, we used high throughput pyrosequencing to characterize stomach and gut content microbiomes of Crassostrea virginica, the Easter oyster, obtained from two sites, one in Barataria Bay (Hackberry Bay) and the other in Terrebonne Bay (Lake Caillou), Louisiana, USA. Stomach microbiomes in oysters from Hackberry Bay were overwhelmingly dominated by Mollicutes most closely related to Mycoplasma; a more rich community dominated by Planctomyctes occurred in Lake Caillou oyster stomachs. Gut communities for oysters from both sites differed from stomach communities, and harbored a relatively diverse assemblage of phylotypes. Phylotypes most closely related to Shewanella and a Chloroflexi strain dominated the Lake Caillou and Hackberry Bay gut microbiota, respectively. While many members of the stomach and gut microbiomes appeared to be transients or opportunists, a putative core microbiome was identified based on phylotypes that occurred in all stomach or gut samples only. The putative core stomach microbiome comprised 5 OTUs in 3 phyla, while the putative core gut microbiome contained 44 OTUs in 12 phyla. These results collectively revealed novel microbial communities within the oyster digestive system, the functions of the oyster microbiome are largely unknown. Finally, a comparison of microbiomes from Louisiana oysters with bacterial communities reported for other marine invertebrates and fish indicated that molluscan microbiomes were more similar to each other than to microbiomes of polychaetes, decapods and fish.
Methane (CH 4 ) is a valuable fuel, constituting 70-95% of natural gas, and a potent greenhouse gas. Release of CH 4 into the atmosphere contributes to climate change. Biological CH 4 production or methanogenesis is mostly performed by methanogens, a group of strictly anaerobic archaea. The direct substrates for methanogenesis are H 2 plus CO 2 , acetate, formate, methylamines, methanol, methyl sulfides, and ethanol or a secondary alcohol plus CO 2 . In numerous anaerobic niches in nature, methanogenesis facilitates mineralization of complex biopolymers such as carbohydrates, lipids and proteins generated by primary producers. Thus, methanogens are critical players in the global carbon cycle. The same process is used in anaerobic treatment of municipal, industrial and agricultural wastes, reducing the biological pollutants in the wastes and generating methane. It also holds potential for commercial production of natural gas from renewable resources. This process operates in digestive systems of many animals, including cattle, and humans. In contrast, in deep-sea hydrothermal vents methanogenesis is a primary production process, allowing chemosynthesis of biomaterials from H 2 plus CO 2 . In this report we present Gene Ontology (GO) terms that can be used to describe processes, functions and cellular components involved in methanogenic biodegradation and biosynthesis of specialized coenzymes that methanogens use. Some of these GO terms were previously available and the rest were generated in our Microbial Energy Gene Ontology (MENGO) project. A recently discovered non-canonical CH 4 production process is also described. We have performed manual GO annotation of selected methanogenesis genes, based on experimental evidence, providing "gold standards" for machine annotation and automated discovery of methanogenesis genes or systems in diverse genomes. Most of the GO-related information presented in this report is available at the MENGO website (http://www.mengo.biochem.vt.edu/).
Chymotrypsin is an important proteolytic enzyme in the human digestive system that cleaves milk proteins through the hydrolysis reaction, making it an interesting subject to study the activity of milk proteases. In this work, we compared detection of chymotrypsin by spectrophotometric dynamic light scattering (DLS) and quartz crystal microbalance (QCM) methods and determined the limit of chymotrypsin detection (LOD), 0.15 ± 0.01 nM for spectrophotometric, 0.67 ± 0.05 nM for DLS and 1.40 ± 0.30 nM for QCM methods, respectively. The sensors are relatively cheap and are able to detect chymotrypsin in 3035 min. While the optical detection methods are simple to implement, the QCM method is more robust for sample preparation, and allows detection of chymotrypsin in non-transparent samples. We give an overview on methods and instruments for detection of chymotrypsin and other milk proteases.
Lignocellulose is a promising feedstock for biofuel production as a renewable, carbohydrate-rich and globally abundant source of biomass. However, challenges faced include environmental and/or financial costs associated with typical lignocellulose pretreatments needed to overcome the natural recalcitrance of the material before conversion to biofuel. Anaerobic fungi are a group of underexplored microorganisms belonging to the early diverging phylum Neocallimastigomycota and are native to the intricately evolved digestive system of mammalian herbivores. Anaerobic fungi have promising potential for application in biofuel production processes due to the combination of their highly effective ability to hydrolyse lignocellulose and capability to convert this substrate to H2 and ethanol. Furthermore, they can produce volatile fatty acid precursors for subsequent biological conversion to H2 or CH4 by other microorganisms. The complex biological characteristics of their natural habitat are described, and these features are contextualised towards the development of suitable industrial systems for in vitro growth. Moreover, progress towards achieving that goal is reviewed in terms of process and genetic engineering. In addition, emerging opportunities are presented for the use of anaerobic fungi for lignocellulose pretreatment; dark fermentation; bioethanol production; and the potential for integration with methanogenesis, microbial electrolysis cells and photofermentation.
Virtual reality (VR) when defined as a computer generated, immersive, three dimensional graphics environment which provides varying degrees of interactivity, remains an expensive, highly specialized application, yet to find its way into the school, home, or business. As a novel approach to a theme park-type attraction, though, its use can be justified. This paper describes how a virtual reality 'tour of the human digestive system' was created for the Omniplex Science Museum of Oklahoma City, Oklahoma. The customers main objectives were: (1) to educate; (2) to entertain; (3) to draw visitors; and (4) to generate revenue. The 'Edutainment' system ultimately delivered met these goals. As more such systems come into existence the resulting library of licensable programs will greatly reduce development costs to individual institutions.
Astronauts use medications for the treatment of a variety of illnesses during space travel. Data mining efforts to assess minor clinical conditions occurring during Shuttle flights STS-1 through STS-94 revealed that space motion sickness (SMS) was the most common ailment during early flight days, occurring in approx.40% of crewmembers, followed by digestive system disturbances (9%) and infectious diseases, which most commonly involved the respiratory or urinary tracts. A more recent analysis of postflight medical debriefs data to examine trends with respect to medication use by astronauts during spaceflights indicated that ~37% of all prescriptions recorded was for pain followed by sleep (22%), SMS (18%), decongestion (14%), and all others (14%). Further analysis revealed that about 150 of 317 crewmembers experienced symptoms of SMS. Nearly all (132 of 150) crewmembers took medication for the treatment of symptoms with a total of 387 doses. Promethazine was taken most often (201 doses); in most cases this resulted in alleviation of symptoms with 130 crewmembers (65%) reporting feeling much or somewhat better. Although fewer total doses of the combination of promethazine and dextroamphetamine (Phen/Dex) were taken (45 doses), slightly more than half of these doses resulted in improvement. The combination of scopolamine and dextroamphetamine (Scop/Dex) was reported to be effective in only 37% of cases, with 36 of 97 total doses resulting in improvement. A higher percentage (24%) of Scop/Dex doses was reported to be ineffective compared with promethazine alone or as Phen/Dex (10% and 7%, respectively). Comparisons of the effectiveness of the different dosage forms of promethazine revealed that intramuscular injection was most effective in alleviating symptoms with 55% feeling much better, 16% feeling somewhat better, and only 7% feeling no effect or worse. Overall, it appears that promethazine alone was used more frequently during flight and was reported effective for the treatment of SMS.
Infection of mouse oligodendrocytes with a recombinant mouse hepatitis virus (MHV) expressing a green fluorescence protein facilitated specific selection of virus-infected cells and subsequent establishment of persistence. Interestingly, while viral genomic RNAs persisted in infected cells over 14 subsequent passages with concomitant synthesis of viral subgenomic mRNAs and structural proteins, no infectious virus was isolated beyond passage 2. Further biochemical and electron microscopic analyses revealed that virions, while assembled, contained little spike in the envelope, indicating that lack of infectivity during persistence was likely due to deficiency in spike incorporation. This type of non-lytic, non-productive persistence in oligodendrocytes is unique among animal viruses and resembles MHV persistence previously observed in the mouse central nervous system. Thus, establishment of such a culture system that can recapitulate the in vivo phenomenon will provide a powerful approach for elucidating the mechanisms of coronavirus persistence in glial cells at the cellular and molecular levels.
Ribonuclease digest of aminoacyl-sRNA in incomplete peptide chain liberation by amino acid- nucleotide fragments attachment to C-terminal