Objective: To validate the performance of 3T spin-echo echo-planar imaging (SE-EPI) magnetic resonance elastography (MRE) for staging hepatic fibrosis in a large population, using surgical specimens ...as the reference standard. Materials and Methods: This retrospective study initially included 310 adults (155 undergoing hepatic resection and 155 undergoing donor hepatectomy) with histopathologic results from surgical liver specimens. They underwent 3T SE-EPI MRE ≤ 3 months prior to surgery. Demographic findings, underlying liver disease, and hepatic fibrosis pathologic stage according to METAVIR were recorded. Liver stiffness (LS) was measured by two radiologists, and inter-reader reproducibility was evaluated using the intraclass correlation coefficient (ICC). The mean LS of each fibrosis stage (F0-F4) was calculated in total and for each etiologic subgroup. Comparisons among subgroups were performed using the Kruskal-Wallis test and Conover post-hoc test. The cutoff values for fibrosis staging were estimated using receiver operating characteristic (ROC) curve analysis. Results: Inter-reader reproducibility was excellent (ICC, 0.98; 95% confidence interval, 0.97-0.99). The mean LS values were 1.91, 2.41, 3.24, and 5.41 kPa in F0-F1 (n = 171), F2 (n = 26), F3 (n = 38), and F4 (n = 72), respectively. The discriminating cutoff values for diagnosing ≥ F2, ≥ F3, and F4 were 2.18, 2.71, and 3.15 kPa, respectively, with the ROC curve areas of 0.97-0.98 (sensitivity 91.2%-95.9%, specificity 90.7%-99.0%). The mean LS was significantly higher in patients with cirrhosis (F4) of nonviral causes, such as primary biliary cirrhosis (9.56 kPa) and alcoholic liver disease (7.17 kPa) than in those with hepatitis B or C cirrhosis (4.28 and 4.92 kPa, respectively). There were no statistically significant differences in LS among the different etiologic subgroups in the F0-F3 stages. Conclusion: The 3T SE-EPI MRE demonstrated high interobserver reproducibility, and our criteria for staging hepatic fibrosis showed high diagnostic performance. LS was significantly higher in patients with non-viral cirrhosis than in those with viral cirrhosis.
Toll-like receptor 3 (TLR3) and melanoma differentiation-associated gene 5 (MDA5) are double-stranded RNA (dsRNA)-recognizing receptors that mediate innate immune responses to virus infection. ...However, the roles played by these receptors in the pathogenesis of avian viruses are poorly understood. In this study, we generated TLR3 and MDA5 single knockout (SKO) and TLR3-MDA5 double knockout (DKO) quail fibroblast cells and examined dsRNA receptor-mediated innate immune responses
. The knockout cells were then stimulated with a synthetic dsRNA ligand polyinosinic:polycytidylic acid poly(I:C) or influenza A virus. Endosomal stimulation of TLR3 by adding poly(I:C) in cell culture media or cytoplasmic stimulation of MDA5 by transfecting poly(I:C) resulted in significant increases of TLR3, MDA5, interferon (IFN) β, and interleukin 8 gene expression levels in wild type (WT) cells. Endosomal poly(I:C) treatment induced a higher level expression of most of the genes tested in MDA5 SKO cells compared with WT cells, but not in TLR3 SKO and DKO cells. Cytoplasmic transfection of poly(I:C) led to significant upregulation of all four genes in WT, TLR3 SKO, and MDA5 SKO cells at 8 hr posttransfection and negligible gene expression changes in TLR3-MDA5 DKO cells. Upon infection with a strain of influenza virus with compromised IFN antagonistic capability, WT cells produced the highest amount of biologically active type I IFN followed by TLR3 SKO and MDA5 SKO cells. DKO cells did not produce detectable amounts of type I IFN. However, the IFN did not induce an antiviral state fast enough to block virus replication, even in WT cells under the experimental conditions employed. In summary, our data demonstrate that TLR3 and MDA5 are the key functional dsRNA receptors in quail and imply their coordinated roles in the induction of innate immune responses upon virus infection.
Neonatal hypoxic-ischemic brain injury (HIE) remains a major cause of neurologic disabilities. However, many experimental therapies have shown limited successes. We assessed whether human mesenchymal ...stem cells (MSCs) could be transplanted in the HIE rat brain to improve neurologic disabilities. P7 SD rats were either subjected to left carotid artery ligation and hypoxic exposure hypoxia-ischemia (HI) or sham operation and normoxic exposure (sham). On P10, rat pubs received either PKH26-labeled MSCs or buffer via intracardial injection, resulting in four experimental groups: sham-buffer, sham-MSC, HI-buffer, and HI-MSC. Cylinder test and accelerating rotarod test were performed 14, 20, 30, and 40 d after injection. Six weeks after injection, cresyl violet and double immunofluorescence staining were performed. MSCs were transplanted to the whole brain mainly after HI. Glial fibrillary acidic protein and OX42 were more abundantly colocalized with MSC than neuronal specific nuclear protein or myelin basic protein. There were no significant differences in the total amounts and cell types between the lesioned and nonlesioned hemisphere. The lesioned hemispheric volume was decreased after HI (p = 0.012) but not restored by MSC. Neurologic performance was significantly impaired only on the cylinder test after HI (p = 0.034), and MSC transplants improved it (p = 0.010). These suggest MSC can be a candidate for the treatment of neonatal HIE.
Nanophotonics capable of directing radiation or enhancing quantum-emitter transition rates rely on plasmonic nanoantennas. We present here a novel Babinet-inverted magnetic-dipole-fed multislot ...optical Yagi–Uda antenna that exhibits highly unidirectional radiation to free space, achieved by engineering the relative phase of the interacting surface plasmon polaritons between the slot elements. The unique features of this nanoantenna can be harnessed for realizing energy transfer from one waveguide to another by working as a future “optical via”.
Elasticity is an important indicator of tissue health, with increased stiffness pointing to an increased risk of cancer. We investigated a tissue inclusion characterization method for the application ...of early breast tumor identification. A tactile sensation imaging system (TSIS) is developed to capture images of the embedded lesions using total internal reflection principle. From tactile images, we developed a novel method to estimate that size, depth, and elasticity of the embedded lesion using 3-D finite-element-model-based forward algorithm, and neural-network-based inversion algorithm are employed. The proposed characterization method was validated by the realistic tissue phantom with inclusions to emulate the tumors. The experimental results showed that, the proposed characterization method estimated the size, depth, and Young's modulus of a tissue inclusion with 6.98%, 7.17%, and 5.07% relative errors, respectively. A pilot clinical study was also performed to characterize the lesion of human breast cancer patients using TSIS.
PurposeOral sulfate tablets are abundantly used for bowel preparation before colonoscopy. However, their efficiency and safety for bowel preparation before colorectal surgery remain ill-defined. ...Herein, we aimed to compare the surgical site infection rates and efficiency between oral sulfate tablets and sodium picosulfate. MethodsWe designed a prospective, randomized, phase 2 clinical trial. Patients with colorectal cancer aged 19-75 years who underwent elective bowel resection and anastomosis by minimally invasive surgery were administered oral sulfate tablets or sodium picosulfate. Eighty-three cases were analyzed from October 2020 to December 2021. Surgical site infection within 30 days after surgery was considered the primary endpoint. Postoperative morbidities, the degree of bowel cleansing, and tolerability were the secondary endpoints. ResultsSurgical site infection was detected in 1 patient (2.5%) in the oral sulfate tablet group and 2 patients (4.7%) in the sodium picosulfate group, indicating no significant difference between the 2 groups. Postoperative morbidity and the degree of bowel cleansing bore no statistically significant differences. Furthermore, none of the investigated tolerability criteria, namely bloating, pain, nausea, vomiting, and discomfort, differed significantly between the 2 groups. The patients' willingness to reuse the drug was also not significantly different between the 2 groups. ConclusionAlthough we could not establish the noninferiority of oral sulfate tablets to sodium picosulfate, we found no evidence suggesting that oral sulfate tablets are less safe or tolerable than sodium picosulfate in preoperative bowel preparation.
Autophagy in neutrophils Shrestha, Sanjeeb; Lee, Jae Man; Hong, Chang-Won
The Korean journal of physiology & pharmacology,
01/2020, Volume:
24, Issue:
1
Journal Article
Peer reviewed
Open access
Autophagy is a highly conserved intracellular degradation and energy-recycling mechanism that contributes to the maintenance of cellular homeostasis. Extensive researches over the past decades have ...defined the role of autophagy innate immune cells. In this review, we describe the current state of knowledge regarding the role of autophagy in neutrophil biology and a picture of molecular mechanism underlying autophagy in neutrophils. Neutrophils are professional phagocytes that comprise the first line of defense against pathogen. Autophagy machineries are highly conserved in neutrophils. Autophagy is not only involved in generalized function of neutrophils such as differentiation in bone marrow but also plays crucial role effector functions of neutrophils such as granule formation, degranulation, neutrophil extracellular traps release, cytokine production, bactericidal activity and controlling inflammation. This review outlines the current understanding of autophagy in neutrophils and provides insight towards identification of novel therapeutics targeting autophagy in neutrophils.
The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform ...metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.
Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil ...extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROS-independent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARS-CoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.
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