Transcriptional Regulator TonEBP Mediates Oxidative Damages in Ischemic Kidney Injury

TonEBP (tonicity-responsive enhancer binding protein) is a transcriptional regulator whose expression is elevated in response to various forms of stress including hyperglycemia, inflammation, and hypoxia. Here we investigated the role of TonEBP in acute kidney injury (AKI) using a line of TonEBP haplo-deficient mice subjected to bilateral renal ischemia followed by reperfusion (I/R). In the TonEBP haplo-deficient animals, induction of TonEBP, oxidative stress, inflammation, cell death, and functional injury in the kidney in response to I/R were all reduced. Analyses of renal transcriptome revealed that genes in several cellular pathways including peroxisome and mitochondrial inner membrane were suppressed in response to I/R, and the suppression was relieved in the TonEBP deficiency. Production of reactive oxygen species (ROS) and the cellular injury was reproduced in a renal epithelial cell line in response to hypoxia, ATP depletion, or hydrogen peroxide. The knockdown of TonEBP reduced ROS production and cellular injury in correlation with increased expression of the suppressed genes. The cellular injury was also blocked by inhibitors of necrosis. These results demonstrate that ischemic insult suppresses many genes involved in cellular metabolism leading to local oxidative stress by way of TonEBP induction. Thus, TonEBP is a promising target to prevent AKI

Resting-state EEG activity related to impulsivity in gambling disorder

Background and aims Impulsivity is a core feature of gambling disorder (GD) and is related to the treatment response. Thus, it is of interest to determine objective neurobiological markers associated with impulsivity in GD. We explored resting-state electroencephalographic (EEG) activity in patients with GD according to the degree of impulsivity. Methods In total, 109 GD subjects were divided into three groups according to Barratt impulsiveness scale-11 (BIS-11) scores: high (HI; 25th percentile of BIS-11 scores, n = 29), middle (MI; 26th–74th percentile, n = 57), and low-impulsivity (LI) groups (75th percentile, n = 23). We used generalized estimating equations to analyze differences in EEG absolute power considering group (HI, MI, and LI), brain region (frontal, central, and posterior), and hemisphere (left, midline, and right) for each frequency band (delta, theta, alpha, beta, and gamma). Results The results indicated that GD patients in the HI group showed decreased theta absolute power, and decreased alpha and beta absolute power in the left, right, particularly midline frontocentral regions. Discussion and conclusions This study is a novel attempt to reveal impulsive features in GD by neurophysiological methods. The results suggest different EEG patterns among GD patients according to the degree of impulsivity, raising the possibility of neurophysiological objective features in GD and helping clinicians in treating GD patients with impulsive features

Indoor formaldehyde removal over CMK-3

The removal of formaldehyde at low concentrations is important in indoor air pollution research. In this study, mesoporous carbon with a large specific surface area was used for the adsorption of low-concentration indoor formaldehyde. A mesoporous carbon material, CMK-3, was synthesized using the nano-replication method. SBA-15 was used as a mesoporous template. The surface of CMK-3 was activated using a 2N H2SO4 solution and NH3 gas to prepare CMK-3-H2SO4 and CMK-3-NH3, respectively. The activated samples were characterized by N2 adsorption-desorption, X-ray diffraction, and X-ray photoelectron spectroscopy. The formaldehyde adsorption performance of the mesoporous carbons was in the order of CMK-3-NH3 > CMK-3-H2SO4 > CMK-3. The difference in the adsorption performance was explained by oxygen and nitrogen functional groups formed during the activation process and by the specific surface area and pore structure of mesoporous carbon

Sound waves delay tomato fruit ripening by negatively regulating ethylene biosynthesis and signaling genes

AbstractRegulation of tomato fruit ripening may help extend fruit shelf life and prevent losses due to spoilage. Here, tomato fruit were investigated whether sound treatment could delay their ripening. Harvested fruit were treated with low-frequency sound waves (1kHz) for 6h, and then monitored various characteristics of the fruit over 14-days at 23±1°C. Seven days after the treatment, 85% of the treated fruit were green, versus fewer than 50% of the non-treated fruit. Most of the tomato fruit had transitioned to the red ripening stage by 14 days after treatment. Ethylene production and respiration rate were lower in the sound-treated than non-treated tomatoes. Furthermore, changes in surface color and flesh firmness were delayed in the treated fruit. To investigate how sound wave treatment effects on fruit ripening, the expression of ethylene-related genes was analyzed by quantitative real-time RT-PCR analysis. The expression level of several ethylene biosynthetic (ACS2, ACS4, ACO1, E4 and E8) and ripening-regulated (RIN, TAGL1, HB-1, NOR, CNR) genes was influenced by sound wave treatment. These results indicated that sound wave treatment delays tomato fruit ripening by altering the expression of important genes in the ethylene biosynthesis and ethylene signaling pathways

Acute perimyocarditis mimicking acute myocardial infarction in a 12-year-old boy with Duchenne muscular dystrophy

Differential diagnosis of chest pain in the pediatric population is important but can be challenging. A 12-year-old boy with Duchenne muscular dystrophy presented with chest pain, cardiac enzyme elevation, and convex ST elevations in the inferior leads with reciprocal ST depression in the anterior leads on electrocardiogram. Echocardiography on admission revealed normal left ventricular function. Suspecting acute myocardial infarction, we performed invasive coronary angiography, which revealed normal coronary arteries. A follow-up electrocardiogram showed an acute pericarditis pattern with concave ST elevations in most leads and PR depression, and follow-up echocardiography revealed global left ventricular dysfunction, suggestive of acute perimyocarditis. Ibuprofen was administered for acute pericarditis, and a continuous milrinone infusion was commenced for myocardial dysfunction. The chest pain improved by the next day, and the ST segment elevations normalized on day 4. Echocardiography on day 9 revealed improved left ventricular function. The patient was discharged on day 11, and he is doing well without chest pain through 12 months of follow-up. The last electrocardiogram showed normal sinus rhythm without ST change. Differential diagnosis of acute myocardial infarction and acute perimyocarditis is important for proper treatment strategies and the different prognoses of these two conditions

The Characteristics of Action Potentials in Primo Vessels and the Effects of Acetylcholine Injection to the Action Potentials

In a previous study, we found that Primo vessels generate different action potentials in smooth muscles, but this study compared the pulse shape to distinguish the two tissues. Thus, a more sophisticated extracellular experiment was performed in this study using an acetylcholine injection; we then observed changes in the amplitude, FWHM (full width at half maximum), and period to explore Primo vessel function. A third type of pulse was recorded for Primo vessels. We observed fast depolarizing and repolarizing phases for this pulse. Further, its FWHM was 30 ms between smooth muscles and neurons. Acetylcholine affected only the period. The amplitude and FWHM were consistent after injection. Primo-vessels generated action potentials at twice the frequency after injection. From the results, we speculate that Primo-vessels perform a role in transferring signals in a different manner, which may be relevant for acupuncture treatment

Defective Localization With Impaired Tumor Cytotoxicity Contributes to the Immune Escape of NK Cells in Pancreatic Cancer Patients

Tumor-infiltrating lymphocytes (TILs), found in patients with advanced pancreatic ductal adenocarcinoma (PDAC), are shown to correlate with overall survival (OS) rate. Although majority of TILs consist of CD8+/CD4+ T cells, the presence of NK cells and their role in the pathogenesis of PDAC remains elusive. We performed comprehensive analyses of TIL, PBMC, and autologous tumor cells from 80 enrolled resectable PDAC patients to comprehend the NK cell defects within PDAC. Extremely low frequencies of NK cells (<0.5%) were found within PDAC tumors, which was attributable not to the low expression of tumor chemokines, but to the lack of chemokine receptor, CXCR2. Forced expression of CXCR2 in patients' NK cells rendered them capable of trafficking into PDAC. Furthermore, NK cells exhibited impaired cell-mediated killing of autologous PDAC cells, primarily due to insufficient ligation of NKG2D and DNAM-1, and failed to proliferate within the hypoxic tumor microenvironment. Importantly, these defects could be overcome by ex-vivo stimulation of NK cells from such patients. Importantly, when the proliferative capacity of NK cells in vitro was used to stratify patients on the basis of cell expansion, patients whose NK cells proliferated <250-fold experienced significantly lower DFS and OS than those with ≥250-fold. Ex-vivo activation of NK cells restored tumor trafficking and reactivity, hence provided a therapeutic modality while their fold expansion could be a potentially significant prognostic indicator of OS and DFS in such patients

Determinants of timeliness in early childhood vaccination among mothers with vaccination cards in Sindh province, Pakistan:a secondary analysis of cross-sectional survey data

OBJECTIVE: Untimely vaccination refers to receiving the given dose before (early) or after (delayed) the recommended time window. The purpose of this study was to assess the extent of timeliness of childhood vaccinations and examine the determinants of vaccination timeliness in Sindh province, Pakistan. DESIGN: Cross-sectional analysis of data from the 2013 and 2014 Maternal and Child Health Program Indicator Surveys. SETTING: Community-based maternal and child health surveys. PARTICIPANTS: Among 10 200 respondents of Maternal and Child Health Program Indicator Surveys, 1143 women who had a live birth in the 2 years preceding the survey were included. OUTCOMES: At the participants' home, an interviewer asked mothers to show their children's vaccination cards, which contained information regarding vaccinations. Children's vaccination status was categorised into timely or early/delayed compared with vaccination schedule. A logistic regression analysis using Firth's penalised likelihood was performed to identify factors associated with timeliness of vaccinations. RESULTS: 238 children (20.8% of children who received a full set of basic vaccinations) received all vaccinations on schedule among children who received a full set of basic vaccinations. The percentages of timely vaccinations ranged from 2.3% for second measles vaccination to 89.3% for bacillus Calmette-Guérin. Child's age and place of delivery were associated with timely vaccinations. Older child age and institutional delivery were associated with decreased timely vaccination rate. CONCLUSIONS: Home-based vaccination record is a key tool to improve the timeliness of vaccinations. The redesigned vaccination cards, the new electronic registries for vaccination card information and the vaccination tracking system to remind the second/third vaccination visits may be helpful to improve timely vaccinations for children under 2 years old