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This finding is supposed to facilitate physical adhesion and colonization of V. cholerae in intestinal lumen. The rTcpA moderately stimulated the expression of tlr4 and overexpressed tlr1, both of which are supposed to induce a mucosal protective response against bacterial infection. NOD2 was significantly increased which suggests that it may contribute in pro-inflammatory responses observed in cholera disease. No change in NOD1 expression was seen which might be attributed to the non-invasive nature of V. cholerae as an intestinal pathogen. In conclusion, the rTcpA protein of V. cholerae showed a statistically significant modulatory effect on the human gut epithelium gene expression which would help promising protection in prophylaxis applications.Multiple membrane trafficking networks operate in the eukaryotic cell and are hijacked by viruses to establish infection. Recent studied have highlighted that viruses can exploit distinct pathways depending on the cell type. Japanese encephalitis virus (JEV), a neurotropic flavivirus, can infect neuronal cells through a clathrin-independent endocytic mechanism. To further characterize the membrane trafficking requirements for JEV infection of neuronal cells, we have performed a RNA interference-based study targeting 136 proteins in the human cell line IMR-32. Through quantitative RT-PCR and plaque assays we have validated that JEV infection in neuronal cells was independent of clathrin, and identified host-factors that were crucial for establishment of infection. Several of these proteins were involved in regulation of actin filament organization such as RHOA, RAC1, proteins of the ARP2/3 complex and N-WASP family, LIMK1, PAK1 and ROCK2. The small molecule inhibitors of ARP2/3 complex, CK-548 and of the N-WASP, Wiskostatin inhibited virus replication highlighting the important roles of these proteins in the virus life-cycle. We also identified ATG12, BECN1, VAPA, VAPB and VCP proteins as crucial host-factors for JEV replication across epithelial and neuronal cell lineages.
Emerging evidence has demonstrated that long noncoding RNAs (lncRNAs) may be closely associated with Hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC). In this study, we investigated the expression and functions of a lncRNA, LINC01189, in HCV-associated HCC.
LINC01189 expression was measured in HCC tumors, HCV-infected HCC tumors and HCV-infected HCC cells. LINC01189 was overexpressed in HCV-infected HepG2 cells to measure its function on HCV-correlated cancer proliferation. In HCC cell lines of Huh7 and Hep3B, LINC01189 was upregulated to investigate its effects on cancer cell proliferation and 5-FU chemoresistance. The competing endogenous RNA (ceRNA) target of LINC01189, human microRNA-155-5p (hsa-miR-155-5p) was probed by dual-luciferase assay and qRT-PCR. Hsa-miR-155-5p was upregulated in LINC01189-overexpessed Huh7 and Hep3B cells to investigate their epigenetic correlation on HCC development regulation.
LINC01189 is downregulated in HCV-infected HCC tumors and cell lines. LINC01189 overexpression inhibited HCC cancer cell proliferation and 5-FU chemoresistance. Hsa-miR-155-5p was confirmed to be a ceRNA target of LINC01189 in HCC. Upregulating hsa-miR-155-5p reversed the LINC01189-mediated inhibition on HCC proliferation and 5-FU chemoresistance.
LINC01189 downregulation is associated with HCV infection in HCC, and it has tumor-suppressing effects on HCC development through hsa-miR-155-5p.
LINC01189 downregulation is associated with HCV infection in HCC, and it has tumor-suppressing effects on HCC development through hsa-miR-155-5p.
Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies.
Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software.
Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI 84.31-91.25%) in treatment-experienced patients.
The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.
The SVR rate of GLE+PIB was higher than other regimens. Bay 11-7085 purchase SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.Motor and cognitive functions are organized in large-scale networks in the human brain that interact to enable flexible adaptation of information exchange to ever-changing environmental conditions. In this review, we discuss the unique potential of the consecutive combination of repetitive transcranial magnetic stimulation (rTMS) and functional neuroimaging to probe network organization and reorganization in the healthy and lesioned brain. First, we summarize findings highlighting the flexible (re-)distribution and short-term reorganization in motor and cognitive networks in the healthy brain. Plastic after-effects of rTMS result in large-scale changes on the network level affecting both local and remote activity within the stimulated network as well as interactions between the stimulated and distinct functional networks. While the number of combined rTMS-fMRI studies in patients with brain lesions remains scarce, preliminary evidence suggests that the lesioned brain flexibly (re-)distributes its computationarther delineate how these general mechanisms interact to enable network flexibility. Besides furthering our neurophysiological insights into brain network interactions, identifying approaches to support and enhance adaptive network plasticity may result in clinically relevant diagnostic and treatment approaches.Using movies and narratives as naturalistic stimuli in human neuroimaging studies has yielded significant advances in understanding of cognitive and emotional functions. The relevant literature was reviewed, with emphasis on how the use of naturalistic stimuli has helped advance scientific understanding of human memory, attention, language, emotions, and social cognition in ways that would have been difficult otherwise. These advances include discovering a cortical hierarchy of temporal receptive windows, which supports processing of dynamic information that accumulates over several time scales, such as immediate reactions vs. slowly emerging patterns in social interactions. Naturalistic stimuli have also helped elucidate how the hippocampus supports segmentation and memorization of events in day-to-day life and have afforded insights into attentional brain mechanisms underlying our ability to adopt specific perspectives during natural viewing. Further, neuroimaging studies with naturalistic stimuli have revealed the role of the default-mode network in narrative-processing and in social cognition. Finally, by robustly eliciting genuine emotions, these stimuli have helped elucidate the brain basis of both basic and social emotions apparently manifested as highly overlapping yet distinguishable patterns of brain activity.Traditional magnetoencephalographic (MEG) brain imaging scanners consist of a rigid sensor array surrounding the head; this means that they are maximally sensitive to superficial brain structures. New technology based on optical pumping means that we can now consider more flexible and creative sensor placement. Here we explored the magnetic fields generated by a model of the human hippocampus not only across scalp but also at the roof of the mouth. We found that simulated hippocampal sources gave rise to dipolar field patterns with one scalp surface field extremum at the temporal lobe and a corresponding maximum or minimum at the roof of the mouth. We then constructed a fitted dental mould to accommodate an Optically Pumped Magnetometer (OPM). We collected data using a previously validated hippocampal-dependant task to test the empirical utility of a mouth-based sensor, with an accompanying array of left and right temporal lobe OPMs. We found that the mouth sensor showed the greatest task-related theta power change. We found that this sensor had a mild effect on the reconstructed power in the hippocampus (~10% change) but that coherence images between the mouth sensor and reconstructed source images showed a global maximum in the right hippocampus. We conclude that augmenting a scalp-based MEG array with sensors in the mouth shows unique promise for both basic scientists and clinicians interested in interrogating the hippocampus.Deep brain stimulation (DBS) is an effective treatment method for a range of neurological and psychiatric disorders. It involves implantation of stimulating electrodes in a precisely guided fashion into subcortical structures and, at a later stage, chronic stimulation of these structures with an implantable pulse generator. While the DBS surgery makes it possible to both record brain activity and stimulate parts of the brain that are difficult to reach with non-invasive techniques, electroencephalography (EEG) and magnetoencephalography (MEG) provide complementary information from other brain areas, which can be used to characterize brain networks targeted through DBS. This requires, however, the careful consideration of different types of artifacts in the data acquisition and the subsequent analyses. Here, we review both the technical issues associated with EEG/MEG recordings in DBS patients and the experimental findings to date. One major line of research is simultaneous recording of local field potentials es, the use of network biomarkers may facilitate the integration of circuit physiology into clinical decision making.Sleep spindles are crucial to memory consolidation. Cortical gamma oscillations (30-100 Hz) are considered to reflect processing of memory in local cortical networks. The temporal and regulatory relationship between spindles and gamma activity might therefore provide clues into how sleep strengthens cortical memory representations. Here, combining EEG with MEG recordings during sleep in healthy humans (n = 12), we investigated the temporal relationships of cortical gamma band activity, always measured by MEG, during fast (12-16 Hz) and slow (8-12 Hz) sleep spindles detected in the EEG or MEG. Time-frequency distributions did not show a consistent coupling of gamma to the spindle oscillation, although activity in the low gamma (30-40 Hz) and neighboring beta range ( less then 30 Hz) was generally increased during spindles. However, more fine-grained analyses of cross-frequency interactions revealed that both low and high gamma power (30-100 Hz) was coupled to the phase of slow and fast EEG spindles, importantly, with this coupling at a fixed phase only for the oscillations within an individual spindle, but with variable phase across spindles.
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