This study aims to identify clinical variables that could affect successful weaning from nasal continuous positive airway pressure (NCPAP) in very preterm infants. Infants born at a gestational age ...(GA) of <32 weeks were retrospectively enrolled. Weaning from NCPAP was initiated when the infants were clinically stable. In the univariate analysis, GA, birth weight, body weight (BW) z-score at the time of successful NCPAP weaning, intubation, total duration of intubation, respiratory distress syndrome grade, APGAR score at the 1 and 5 min, initial shock, anemia, bronchopulmonary dysplasia, number of blood transfusions, total duration of dopamine use, administration of more than two doses of surfactant, use of aminophylline, use of a diuretic, and total duration of total parenteral nutrition were significantly associated with postmenstrual age (PMA) at the time of successful NCPAP weaning. Multivariate analysis showed that the total duration of intubation, bronchopulmonary dysplasia, and administration of more than two doses of surfactant were positively associated with PMA at the time of successful NCPAP weaning. A reverse association was noted between BW z-score and PMA at the time of successful NCPAP weaning. Sufficient nutrition and avoidance of further ventilator-induced lung injury could decrease NCPAP duration in very preterm infants.
Manganese-dependent superoxide dismutase (MnSOD, SodA) and iron-dependent SOD (FeSOD, SodB) are critical cytosolic enzymes for alleviating superoxide stress. Distinct from the singular
gene in most ...bacteria,
harbors two
genes,
and
. The roles of SodA1, SodA2, and SodB of
in alleviating superoxide stress were investigated. The expression of
genes was determined by promoter-
transcriptional fusion assay and qRT-PCR.
and
expressions were proportional to the bacterial logarithmic growth, but unaffected by menadione (MD), iron, or manganese challenges. SodA1 was intrinsically unexpressed and inducibly expressed by MD. Complementary expression of
was observed when
was inactivated. The individual or combined
deletion mutants were constructed using the gene replacement strategy. The functions of SODs were assessed by evaluating cell viabilities of different
mutants in MD, low iron-stressed, and/or low manganese-stressed conditions. Inactivation of SodA1 or SodA2 alone did not affect bacterial viability; however, simultaneously inactivating
and
significantly compromised bacterial viability in both aerobic growth and stressed conditions. SodA1 can either rescue or support SodA2 when SodA2 is defective or insufficiently potent. The presence of two MnSODs gives
an advantage against superoxide stress.
Curcumin is one of the most valuable natural products due to its pharmacological activities. However, the low bioavailability of curcumin has long been a problem for its medicinal use. Large studies ...have been conducted to improve the use of curcumin; among these studies, curcumin metabolites have become a relatively new research focus over the past few years. Additionally, accumulating evidence suggests that curcumin or curcuminoid metabolites have similar or better biological activity than the precursor of curcumin. Recent studies focus on the protective role of plasma tetrahydrocurcumin (THC), a main metabolite of curcumin, against tumors and chronic inflammatory diseases. Nevertheless, studies of THC in eye diseases have not yet been conducted. Since ophthalmic conditions play a crucial role in worldwide public health, the prevention and treatment of ophthalmic diseases are of great concern. Therefore, the present study investigated the antioxidative, anti-inflammatory, antiangiogenic, and neuroprotective effects of THC on four major ocular diseases: age-related cataracts, glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). While this study aimed to show curcumin as a promising potential solution for eye conditions and discusses the involved mechanistic pathways, further work is required for the clinical application of curcumin.
The emergence of carbapenemase-producing Klebsiella pneumoniae (CPKP) has become a great concern worldwide. In this study, 994 non-duplicate, carbapenem non-susceptible Klebsiella pneumonia isolates ...were collected in Taiwan from 2011 to 2013 for detection of the carbapenemase genes, assessment of antimicrobial susceptibility and molecular epidemiology studies. Of these 994 isolates, 183 (18.4%) had carbapenemase genes: 157 (15.8%) KPC (145 KPC-2 and 12 KPC-17), 16 (1.6%) IMP-8, 9 (0.9%) VIM-1, and 1 (0.1%) NDM-1. KPC had the highest prevalence rate among the carbapenemases and represented a major epidemic clone circulating in Taiwan. The ST512 and ST258 KPC-2 KPs were first identified in Taiwan and were grouped into a small cluster in the PFGE profile. In addition, the genetic structure encompassing the blaKPC gene of the ST512 and ST258 isolates showed a different pattern from that of other KPC isolates. ST11 may be a major sequence type circulating in Taiwan, although a specific minor clone has begun to be observed. This is the first report of ST258 and ST512 KPC-2 KP isolates in Taiwan, whether ST258 and ST512 will become the next endemic problems in Taiwan should be closely monitored.
Chloroplasts are the sites for photosynthesis, and two Golden2-like factors act as transcriptional activators of chloroplast development in rice (Oryza sativa L.) and maize (Zea mays L.). Rice OsGLK1 ...and OsGLK2 are orthologous to maize ZmGLK1 (ZmG1) and ZmGLK2 (ZmG2), respectively. However, while rice OsGLK1 and OsGLK2 act redundantly to regulate chloroplast development in mesophyll cells, maize ZmG1 and ZmG2 are functionally specialized and expressed in different cell-specific manners. To boost rice chloroplast development and photosynthesis, we generated transgenic rice plants overexpressing ZmG1 and ZmG2, individually or simultaneously, with constitutive promoters (pZmUbi::ZmG1 and p35S::ZmG2) or maize promoters (pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2). Both ZmG1 and ZmG2 genes were highly expressed in transgenic rice leaves. Moreover, ZmG1 and ZmG2 showed coordinated expression in pZmG1::ZmG1/pZmG2::ZmG2 plants. All Golden2-like (GLK) transgenic plants had higher chlorophyll and protein contents, Rubisco activities and photosynthetic rates per unit leaf area in flag leaves. However, the highest grain yields occurred when maize promoters were used; pZmG1::ZmG1, pZmG2::ZmG2, and pZmG1::ZmG1/pZmG2::ZmG2 transgenic plants showed increases in grain yield by 51%, 47%, and 70%, respectively. In contrast, the pZmUbi::ZmG1 plant produced smaller seeds without yield increases. Transcriptome analysis indicated that maize GLKs act as master regulators promoting the expression of both photosynthesis-related and stress-responsive regulatory genes in both rice shoot and root. Thus, by promoting these important functions under the control of their own promoters, maize GLK1 and GLK2 genes together dramatically improved rice photosynthetic performance and productivity. A similar approach can potentially improve the productivity of many other crops.
Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and ...its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.
Autophagy related protease 4B (ATG4B) is a protease required for autophagy processing, which is strongly implicated in cancer progression. Phosphorylation of ATG4B is crucial for activation of its ...protease activity. However, little is known about the relationship of ATG4B and its phosphorylated form at Ser 383 and 392 sites (pS383/392-ATG4B), with clinical outcomes, particularly in colorectal cancer (CRC).
The ATG4B gene expression in CRC patients was obtained from The Cancer Genome Atlas (TCGA) database to analyze its clinical relevance. Tissue microarrays composed of 118 CRC patient specimens were used to determine the associations of ATG4B and pS383/392-ATG4B protein levels with prognosis. The biological functions of ATG4B in CRC cells were inspected with cell proliferation, mobility and spheroid culture assays.
ATG4B gene expression was elevated in tumor tissues of CRC patients compared to that in adjacent normal tissues and high level of ATG4B expression was associated with poor survival. Similarly, protein levels of ATG4B and pS383/392-ATG4B were highly correlated with worse overall survival and disease-free survival. Stratification analysis results showed that high level of ATG4B had significantly higher risk of mortality in males and elderly patients compared to those female patients and patients 60 years or younger. In contrast, multivariate Cox's regression analysis indicated that high level of pS383/392-ATG4B was significantly linked to unfavorable overall survival and disease-free survival of males and elderly patients, whereas, it had no correlation with female patients and patients 60 years or younger. Moreover, high level of ATG4B was positively associated with increased mortality risk in patients with advanced AJCC stages (III and IV) and lymph node invasion (N1 and N2) for both overall survival and disease-free survival. Nevertheless, high level of pS383/392-ATG4B was positively correlated with increased mortality risk in patients with early AJCC stages (I and II) and without lymph node invasion (N0). In addition, silencing ATG4B attenuated migration, invasion, and further enhanced the cytotoxic effects of chemotherapeutic drugs in two and three-dimensional cultures of CRC cells.
Our results suggest that ATG4B and pS383/392-ATG4B might be suitable biomarkers and therapeutic targets for CRC.
Purpose
Positron emission tomography/computed tomography (PET/CT) is an important tool for tumor staging or treatment response evaluation, especially for lung tumors. However, the captured static PET ...image could be blurry due to patients' free breathing, resulting in decreased image quality and incorrect quantitative values. This study aimed to evaluate whether the Q.Static scan mode with the novel PET list data-driven gated (DDG) technique decreases the lesion blurring problems in the PET/CT images of patients with lung cancer.
Methods
Data of 194 patients with lung tumors were retrospectively reviewed. DDG Q.Static scan mode was set up in three beds to cover the whole chest and the upper abdomen in the routine PET/CT scans and was activated automatically when sensing significant respiratory motion. Routine reconstruction algorithm was applied for data analysis. Only the lesions in the motion-corrected areas were measured and calculated for statistics.
Results
Among the 194 patients, 124 had at least one bed that activated the DDG Q.Static procedure. However, only 49 out of the 124 patients showed lesions in their activated beds. Compared with the non-corrected data, the DDG Q.Static data showed improved accuracy with increased SUV
max
and SUV
mean
of 8.52% (9.20 ± 5.42 to 9.74 ± 5.42) and 8.65% (6.11 ± 3.68 to 6.48 ± 3.68), respectively. In addition, metabolic tumor volume was reduced from 6.54 ± 8.58 to 5.55 ± 7.33 (14.79% reduction). For subjective image quality, the DDG Q.Static data scored higher than the non-corrected data.
Conclusion
This study showed that the quantitative values and image quality were improved after the correction. Therefore, the DDG Q.Static technique is an effective method to correct motion artifacts in PET/CT scans.
Imipenem-relebactam is a new β-lactam and β-lactamase inhibitor combination to treat carbapenem-resistant gram-negative bacteria infections. However, difference in carbapenem resistant mechanisms ...existed with geographic variations.
To evaluate the susceptibility of imipenem-relebactam to 660 carbapenem-nonsusceptible Enterobacteriaceae isolates in Taiwan and to identify the in vivo efficacy with a Caenorhabditis elegans model.
188 carbapenem-nonsusceptible Escherichia coli isolates and 472 carbapenem-nonsusceptible Klebsiella pneumoniae isolates were collected from a national surveillance study in Taiwan. The antimicrobial susceptibility profiles and carbapenemase distributions were determined. An agar dilution method was performed to evaluate the in vitro activities of imipenem monotherapy and imipenem-relebactam combination. Contributions of metallo-carbapenemase to imipenem-relebactam susceptibility was investigated via EDTA treatment. A C. elegans model was used to evaluate the in vivo efficacy of imipenem-relebactam combination.
87.8% and 82.2% susceptibility to imipenem-relebactam was observed for 188 carbapenem-nonsusceptible E. coli and 472 carbapenem-nonsusceptible K. pneumoniae, respectively. However, poor activities of imipenem-relebactam was observed against 23 metallo-carbapenemase producers tested in this study. In the in vivo C. elegans model, imipenem-relebactam significantly rescued nematodes from the infection of a blaKPC-producing K. pneumoniae isolate.
Our study supports that imipenem-relebactam is a potential therapy against carbapenem-nonsusceptible Enterobacteriaceae, and to our knowledge, this is the first report of evaluation for imipenem-relebactam efficacy against carbapenem-nonsusceptible Enterobacteriaceae in Taiwan.
Background. Chronic lung disease (CLD), most commonly seen in premature infants who required mechanical ventilation, is associated with functional consequences on lungs and respiratory morbidity. ...This study aimed to evaluate the lung function of premature infants before discharge and their relevant factors related to the lung function. Methods. Very low birth weight (VLBW) preterm infants, who required respiratory support soon after birth and were admitted to a hospital in Taiwan, were enrolled. Infants with a need for supplemental oxygen or positive-pressure ventilation support at the postmenstrual age (PMA) of 36 weeks were diagnosed with CLD. Lung function was examined once using EXHALYZER® D before infants were ready for discharge. Results. Forty-five VLBW preterm infants received the lung function test before discharge, 27 of whom were diagnosed with CLD. The gestational age (p=0.001) and birth weight (p<0.001) were smaller in the CLD group than in the no-CLD group. Furthermore, infants with CLD required a longer duration of respiratory support (p<0.001). The postnatal age and PMA were higher and body size was bigger in infants with CLD on lung function measurement. However, lung function was comparable between the groups. The functional residual capacity and tidal volume were associated with body size upon measuring lung function among all VLBW premature infants. FRC was positively correlated with the body length on measuring lung function in those with CLD. Conclusion. In our study, we showed FRC was positively related to the PMA and body length and tidal volume was positively correlated with the body weight and length on lung function measurement in VLBW preterm infants before discharge. Moreover, FRC was positively correlated with the body length on measuring lung function in those with CLD. The lung volume, ventilation, and respiratory mechanics on discharge were comparable between CLD and no-CLD groups.
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