Tributyltin-binding protein type 1 has a distinctive lipocalin-like structure and is involved in the excretion of tributyltin in Japanese flounder, Paralichthys olivaceus

Tributyltin-binding protein type 1 (TBT-bp1) is a newly discovered protein that binds with TBT in the blood of the Japanese flounder, Paralichthys olivaceus. We determined the genomic sequence of TBT-bp1 and found that this protein has a conserved exon–intron structure that is common to the lipocalin protein family. The secondary and tertiary structures of TBT-bp1, predicted from amino acid sequence, included at least two α-helices and eight β-sheets that are conserved in all lipocalins and form a barrel structure that may bind with ligands. Analysis of the gene structure, secondary structure, and tertiary structure demonstrated that TBT-bp1 could be classified as a lipocalin. A homology search revealed the presence of TBT-bp1-like proteins in eight species of teleost. When flounder were injected intraperitoneally with TBT-d27 at 11.6 μg/fish, TBT-d27 was detected in the blood and in the skin mucus. The concentration of TBT-d27 in mucus was approximately 1/100 of that in the serum. Western blotting analysis revealed that TBT-bp1 was present in the skin mucus. These results suggest that TBT-bp1 in Japanese flounder binds with TBT and is excreted from the body via the mucus.     

CuO Bionanocomposite with Enhanced Stability and Antibacterial Activity against Extended-Spectrum Beta-Lactamase Strains

Worldwide, bacterial resistance to beta-lactam antibiotics is the greatest challenge in public health care. To overcome the issue, metal-based nanoparticles were extensively used as an alternative to traditional antibiotics. However, their unstable nature limits their use. In the present study a very simple, environmentally friendly, one-pot synthesis method that avoids the use of organic solvents has been proposed to design stable, novel nanocomposites. Formulation was done by mixing biogenic copper oxide (CuO) nanomaterial with glycerol and phospholipids isolated from egg yolk in an appropriate ratio at optimum conditions. Characterization was done using dynamic light scattering DLS, Zeta potential, high performance liquid chromatography (HPLC), and transmission electron microscopy (TEM). Further, its antibacterial activity was evaluated against the extended-spectrum beta-lactamase strains based on zone of inhibition and minimal inhibitory concentration (MIC) indices. Results from this study have demonstrated the formulation of stable nanocomposites with a zeta potential of 34.9 mV. TEM results indicated clear dispersed particles with an average of 59.3 ± 5 nm size. Furthermore, HPLC analysis of the egg yolk extract exhibits the presence of phospholipids in the sample and has significance in terms of stability. The newly formed nanocomposite has momentous antibacterial activity with MIC 62.5 μg/mL. The results suggest that it could be a good candidate for drug delivery in terms of bactericidal therapeutic applications.     

Association between anemia and postoperative complications in infants undergoing pyloromyotomy

BackgroundAlthough preoperative anemia has been suggested to predict postsurgical morbidity and mortality among infants < 1 year of age, the data were drawn from heterogeneous patient cohorts including severely ill infants undergoing complex, high-risk procedures. We aimed to determine whether untreated preoperative anemia was associated with increased risk of postoperative complications in infants < 1 year of age who underwent pyloromyotomy, a common and relatively simple surgery.MethodsInfants < 1 year of age undergoing pyloromyotomy were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program-Pediatric database. Preoperative anemia was defined as a hematocrit ≤ 40% for infants 0–30 days of age and ≤ 30% for infants more than 30 days of age. Patients who received pre- or postoperative blood transfusions were excluded.ResultsWe identified 2948 patients who met our inclusion criteria, of whom 843 were anemic (29%). The overall rate of complications in this cohort was 6%. The most common postoperative complications were readmission (97 cases), surgical site infection (43), reoperation (39), prolonged hospital stay (24), urinary tract infection (3), 30-day mortality (3) and cardiac arrest (2). We found no differences in the incidence of complications in anemic versus nonanemic patients on bivariate analysis or multivariable logistic regression (adjusted odds ratio = 1.2; 95% confidence interval: 0.8–1.7; P = 0.319).ConclusionsIn relatively healthy infants undergoing pyloromyotomy, untreated preoperative anemia was not associated with postoperative compilations and should not be considered a significant risk factor.Level of evidence III.     

Takotsubo syndrome: The past,the present and the future

Takotsubo syndrome is a wide spectrum disease with a dramatic clinical presentation mimicking acute coronary syndrome albeit without obstructive coronary disease and typically manifests in the backdrop of intense emotional or physical trigger. Pathophysiology is incompletely understood with multifactorial mechanistic pathways circling around a heart-brain-endocrine axis. Several anatomic and phenotypic variants exist with varied clinical manifestations. The aftermath of Takotsubo syndrome is not always benign and both short-and longterm complications can occur which may impact its prognosis. Several gaps in knowledge exist providing an impetus for tremendous future research opportunities.     

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m³ (for one, three, or 10 days). The 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m³ radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m³ radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20–40% (2 kBq/m³ for three days or 20 kBq/m³ for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15–60% and 15–45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage.     

Withaferin A induces p53-dependent apoptosis by repression of HPV oncogenes and upregulation of tumor suppressor proteins in human cervical cancer cells

Cervical cancer is caused by human papilloma virus (HPV) expressing E6 and E7 oncoproteins, which are known to inactivate tumor suppressor proteins p53 and pRb, respectively. Repression of HPV oncoproteins would therefore result in reactivation of tumor suppressor pathways and cause apoptosis in cancer cells. Withaferin A (WA), the active component of the medicinal plant Withania Somnifera, has exhibited inhibitory effects against several different cancers. We examined the activity of WA on human cervical cancer cells in vitro and in vivo. WA potently inhibited proliferation of the cervical cancer cells, CaSki (IC(50) 0.45 ± 0.05 μM). Mechanistically, WA was found to (i) downregulate expression of HPV E6 and E7 oncoproteins, (ii) induce accumulation of p53, (iii) increase levels of p21(cip1/waf1) and its interaction with proliferating cell nuclear antigen (PCNA), (iv) cause G(2)/M cell cycle arrest, associated with modulation of cyclin B1, p34(cdc2) and PCNA levels, (v) decrease the levels of STAT3 and its phosphorylation at Tyr(705) and Ser(727) and (vi) alter expression levels of p53-mediated apoptotic markers-Bcl2, Bax, caspase-3 and cleaved PARP. In vivo, WA resulted in reduction of nearly 70% of the tumor volume in athymic nude mice with essentially similar trend in the modulation of molecular markers as in vitro. This is the first demonstration indicating that WA significantly downregulates expression of HPV E6/E7 oncogenes and restores the p53 pathway, resulting in apoptosis of cervical cancer cells. Together, our data suggest that WA can be exploited as a potent therapeutic agent for the treatment and prevention of cervical cancer without deleterious effects.