Oxygen-induced retinopathy (OIR) animal model is widely used for retinopathy of prematurity (ROP) researches. The purpose of this study was to identify proteins and related pathways of OIR with or ...without anti-vascular endothelial growth factor (VEGF) treatment, for use as biomarkers in diagnosing and treating ROP. Nine samples were subjected to proteomic analysis. Retina specimens were collected from 3 OIR mice, 3 OIR mice with anti-VEGF treatment and 3 normal mice (control group). Liquid chromatography-tandem mass spectrometry analysis was performed using the 4D label-free technique. Statistically significant differentially expressed proteins, gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representations, InterPro (IPR) and protein interactions were analyzed. In total, 4585 unique proteins were identified as differentially expressed proteins (DEPs). Enrichment analysis of the GO and KEGG indicated functional clusters related to peptide biosynthetic and metabolic process, cellular macromolecule biosynthetic process and nucleic acid binding in OIR group. For anti-VEGF treatment group, DEPs were clustered in DNA replication, PI3K/Akt signaling pathway and Jak/STAT signaling pathway. Proteomic profiling is useful for the exploration of molecular mechanisms of OIR and mechanisms of anti-VEGF treatment. These findings may be useful for identification of novel biomarkers for ROP pathogenesis and treatment.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pseudorabies virus (PRV) belongs to Alphaherpesvirinae subfamily that causes huge economic loss in pig industry worldwide. It has been recently demonstrated that many herpesviruses encode microRNAs ...(miRNAs), which play crucial roles in viral life cycle. However, the knowledge about PRV-encoded miRNAs is still limited. Here, we report a comprehensive analysis of both viral and host miRNA expression profiles in PRV-infected porcine epithelial cell line (PK-15). Deep sequencing data showed that the ∼4.6 kb intron of the large latency transcript (LLT) functions as a primary microRNA precursor (pri-miRNA) that encodes a cluster of 11 distinct miRNAs in the PRV genome, and 209 known and 39 novel porcine miRNAs were detected. Viral miRNAs were further confirmed by stem-loop RT-PCR and northern blot analysis. Intriguingly, all of these viral miRNAs exhibited terminal heterogeneity both at the 5' and 3' ends. Seven miRNA genes produced mature miRNAs from both arms and two of the viral miRNA genes showed partially overlapped in their precursor regions. Unexpectedly, a terminal loop-derived small RNA with high abundance and one special miRNA offset RNA (moRNA) were processed from a same viral miRNA precursor. The polymorphisms of viral miRNAs shed light on the complexity of host miRNA-processing machinery and viral miRNA-regulatory mechanism. The swine genes and PRV genes were collected for target prediction of the viral miRNAs, revealing a complex network formed by both host and viral genes. GO enrichment analysis of host target genes suggests that PRV miRNAs are involved in complex cellular pathways including cell death, immune system process, metabolic pathway, indicating that these miRNAs play significant roles in virus-cells interaction of PRV and its hosts. Collectively, these data suggest that PRV infected epithelial cell line generates a diverse set of host miRNAs and a special cluster of viral miRNAs, which might facilitate PRV replication in cells.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased arterial stiffness and wave reflections are independently associated with orthostatic hypotension (OH). This study investigated whether heart rate variability (HRV) is also involved in the ...modulation of orthostatic blood pressure (BP) change. A total of 429 subjects (65.1 ± 16.4 years, 77.4% men) were enrolled in this study. OH was defined as a ⩾ 20 mm Hg decrease in brachial systolic blood pressure (SBP) or a ⩾ 10 mm Hg diastolic blood pressure (DBP) decrease upon standing. Measurements of carotid-femoral pulse wave velocity (cf-PWV) and the amplitude of the reflected pressure wave from a decomposed carotid pressure wave (Pb) were obtained by carotid tonometry in the supine position. The power spectrum from a 5-min recording of an electrocardiogram at rest was analyzed to provide components in the high frequency (HF) and low frequency (LF) ranges. Subjects with OH (n = 59, 13.8%) had significantly higher cf-PWV and Pb and significantly lower LogHF and LogLF than those without OH (n = 370). The cf-PWV, Pb, LogHF and LogLF were significantly associated with postural SBP and DBP changes. Furthermore, cf-PWV but not Pb was significantly associated with LogHF and LogLF. Multivariate analysis showed that Pb (odds ratio (OR) per 1 s.d. 1.65, 95% confidence interval (CI) 1.282-2.137; P = 0.003) and LogHF (OR 0.628, 95% CI 0.459-0.860, P = 0.004), but not cf-PWV (OR 1.279, 95% CI 0.932-1.755, P = 0.128), were significant independent determinants of OH. Increased wave reflections may predispose OH independently of arterial stiffness and HRV. In contrast, increased arterial stiffness may cause OH through the modulation of HRV.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The electromechanical activation time (EMAT) normalized by cardiac cycle length (%EMAT) and the third heart sound (S3) strength, as measured by automated acoustic cardiography, are predictive of ...postdischarge adverse events in patients with acute heart failure (AHF). The aim of this study was to evaluate whether the acoustic cardiography-guided management improves outcomes in patients with AHF when it is compared with the conventional therapy.
This prospective single-blind study randomized 225 patients with AHF (74.1 ± 14.5 years of age, 26.2% women, and left ventricular ejection fraction 38.4 ± 14.4%) before discharge to the EMAT-guided group (n = 114) with the postdischarge treatment goals to reduce %EMAT to < 15% and S3 < 5, and the symptom-guided group (n = 111) to adjust medications without knowledge of the results of acoustic cardiography. The primary endpoints were rehospitalization for heart failure and total mortality during 1-year follow-up.
The 2 groups were well matched in age and predischarge %EMAT and S3 strength. After a mean follow-up period of 238.1 ± 140.8 days, a significant reduction in the primary endpoints was seen in the EMAT-guided group compared with the symptom-guided group (43 events vs 61 events, P = 0.0095). Kaplan-Meier curves demonstrated significant differences in the time to first event, favoring the EMAT-guided group in the total study population (n = 225, hazard ratio and 95% confidence interval: 0.61, 0.42–0.91, log-rank P = 0.0129), as well as in the prespecified subgroup of patients with predischarge %EMAT > 15% (n = 85; 0.32, 0.16–0.65, P = 0.0008).
In patients hospitalized due to AHF, EMAT-guided postdischarge management was superior to the conventional symptoms-driven therapy in terms of 1-year outcomes (ClinicalTrials.gov number NCT01298232)
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BRAF inhibitors were approved for the treatment of BRAF-mutant melanoma. However, most patients acquire the resistance to BRAF inhibitors after several months of treatment. miR-524-5p is considered ...as a tumor suppressor in many cancers, including melanoma. In this study, we investigated the biological functions of miR-524-5p in melanoma with acquired resistance to BRAF inhibitor and evaluated the endogenous miR-524-5p expression as a biomarker for melanoma. The results showed that the expression of miR-524-5p was 0.481-fold lower in melanoma tissues (n = 117) than in nevus tissues (n = 40). Overexpression of miR-524-5p significantly reduced proliferative, anchorage-independent growth, migratory and invasive abilities of BRAF inhibitor-resistant melanoma cells. Moreover, the introduction of miR-524-5p led to a reduced development of BRAF inhibitor-resistant melanoma in vivo. Remarkably, the MAPK/ERK signaling pathway was decreased after treatment with miR-524-5p. Furthermore, next-generation sequencing analysis implied that the complement system, leukocyte extravasation, liver X receptor/retinoid-X-receptor activation, and cAMP-mediated signaling may be related to miR-524-5p-induced pathways in the resistant cells. The miR-524-5p level was higher on average in complete response and long-term partial response patients than in progressive disease and short-term partial response patients treated with BRAF inhibitors. Our results proposed that miR-524-5p could be considered as a target for treatment BRAF inhibitor-resistant melanoma and a prognostic marker in the response of patients to BRAF inhibitors for melanoma.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.AimsIn this study, we investigated the risk of stroke following the exposure ...to mood stabilisers in patients with bipolar disorder.
Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case-crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder.
Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke.
Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.Declaration of interestNone.
Abstract
Background
The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) ...remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC.
Methods
The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression.
Results
We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation.
Conclusions
Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Quantum heat transport is considered as an indispensable branch of quantum thermodynamics to potentially improve performance of thermodynamic devices. We theoretically propose a dissipative ...qubit-photon system composed of multiple coupled resonators interacting with a single two-level qubit, to explore the steady-state heat transport by tuning both the inter-resonator photon hopping and the qubit-photon coupling. Specifically in the three-mode case, the dramatic enhancement and suppression of the heat current into the central resonator can be modulated by the corresponding frequency, compared to the currents into two edge resonators. Moreover, fruitful cycle current components are unraveled at weak qubit-photon coupling, which are crucial to exhibit the nonmonotonic feature with increase of the reservoir temperature bias. In the one-dimensional case under the mean-field framework, the influence of the photon hopping on heat transport is analyzed. The steady-state heat current is comparatively enhanced to the single-mode limit at weak qubit-photon coupling, stemming from the nonvanishing mean-field photon excitation parameter and the additional cycle current component. We hope these obtained results may have possible applications in quantum thermodynamic manipulation and energy harvesting.
Purpose: In 2013, medical schools in Taiwan implemented a 6-year medical program that replaced the previous 7-year medical education program. The postgraduate year (PGY) program was also extended ...from 1 year to 2 years. The new program is characterized by diversified teaching, integration of medical skills, a system-oriented curriculum, and the implementation of primary care and clinical thinking training. The purpose of this study was to examine whether postgraduate residents who learned under the new program have better patient care skills than those who learned under the previous program.Methods: Of 101 residents in the PGY program at Taipei Veterans General Hospital, 78 were trained in the 6-year program, while 23 were trained in the 7-year program. During the PGY training, 2 objective structured clinical examinations (OSCEs) were used to evaluate clinical reasoning, communication skills, and procedural skills at the beginning of the training and after 11 months of training, respectively. The scores of each OSCE and the rate of improvement of the pre- and post-tests were analyzed.Results: Residents trained in the new program scored higher on clinical reasoning (P<0.001) and the total scores of the 3 tested skills (P=0.019) on the pre-test. In terms of improvement, residents educated in the previous system improved more in clinical reasoning than those educated in the new education system.Conclusion: The new medical education program, which emphasizes clinical thinking, improved residents’ clinical skills. The PGY program was effective in improving the clinical performance of residents who were educated in the previous system.
This research presents the integration of lean production and radiofrequency identification (RFID) technology to improve the efficiency and effectiveness of warehouse management. More than ten ...million parts belonging to around 10,000 types in a distribution center were involved in this study. There are more than 10,000 storage and retrieval operations for hundreds of part types on a daily basis. Value stream mapping was used to draw current state mapping and future state mapping (with lean management and RFID) with material flow, information flow, and time flow. Preliminary experiments showed that the average reading rate of electric forklift and hydraulic cart are 99.3 and 99.1 % by fixed ultra-high frequency RFID readers with antenna installed at the receiving/shipping dock and passive tags mounted on box/pallet. The processing time of data transmitting to warehouse management system at receiving and shipping docks was reduced by 99 and 89 %, respectively. The total operation time from current stage to future stage with only lean can be saved by 79 %. With further integration of RFID to lean, the total operation time can be saved by 87 %. Moreover, performance on saving total operation time can be enhanced to 91 % with cross-docking. The benefit of using RFID in the warehouse management is realized and promoted.
Full text
Available for:
DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
You have reached the maximum number of search results that are displayed.
For better performance, the search offers a maximum of 1,000 results per query (or 50 pages if the option 10/page is selected).
Consider using result filters or changing the sort order to explore your results further.
PDF
