Bulk binary ZnO–P2O5 glasses with 50–70mol% ZnO were immersed in distilled water at 30–90°C for up to 72h. The immersed samples were characterized by weight loss, the change in solution pH, X-ray ...diffraction (XRD) analysis, scanning electron microscopy and Raman spectroscopy. Weight loss decreased with ZnO concentration for all immersion temperatures. Dissolution behavior was classified into two types in terms of weight loss and macroscopic appearance. Type I was primarily recognized in 50–60mol% ZnO glasses. In type I, the weight loss for 72h was relatively large (>1.0×10−7kgmm−2, >10% of initial sample weight). Raman spectra of the type I glasses indicated that the depolymerization of phosphate glass network occurred during the dissolution process. Crystalline Zn2P2O7·3H2O was precipitated in the water solution after immersion. Type II dissolution behavior was recognized in the 65 and 70mol% ZnO glasses except for the 65ZnO–35P2O5 glass immersed at 90°C. In the type II behavior, the weight loss for 72h was relatively-small (<1.0×10−8kgmm−2, <1% of initial sample weight). The microstructure of the type II glass indicated selective dissolution. The dissolution process of the type II glass is discussed.
Autophagy plays a vital role in cell homeostasis by eliminating nonfunctional components and promoting cell survival. Here, we examined the levels of autophagy signaling proteins after 7 days of ...overload hypertrophy in the extensor digitorum longus (EDL) and soleus muscles of control and diabetic rats. We compared control and 3‐day streptozotocin‐induced diabetic rats, an experimental model for type 1 diabetes mellitus (T1DM). EDL muscles showed increased levels of basal autophagy signaling proteins. The diabetic state did not affect the extent of overload‐induced hypertrophy or the levels of autophagy signaling proteins (p‐ULK1, Beclin‐1, Atg5, Atg12‐5, Atg7, Atg3, LC3‐I and II, and p62) in either muscle. The p‐ULK‐1, Beclin‐1, and p62 protein expression levels were higher in the EDL muscle than in the soleus before the hypertrophic stimulus. On the contrary, the soleus muscle exhibited increased autophagic signaling after overload‐induced hypertrophy, with increases in Beclin‐1, Atg5, Atg12‐5, Atg7, Atg3, and LC3‐I expression in the control and diabetic groups, in addition to p‐ULK‐1 in the control groups. After hypertrophy, Beclin‐1 and Atg5 levels increased in the EDL muscle of both groups, while p‐ULK1 and LC3‐I increased in the control group. In conclusion, the baseline EDL muscle exhibited higher autophagy than the soleus muscle. Although TDM1 promotes skeletal muscle mass loss and strength reduction, it did not significantly alter the extent of overload‐induced hypertrophy and autophagy signaling proteins in EDL and soleus muscles, with the two groups exhibiting different patterns of autophagy activation.
We analyzed autophagy proteins in extensor digitorum longus (EDL) and soleus muscles of control and diabetic rats after 7 days of hypertrophy. Basal autophagy proteins were higher in EDL. Diabetes did not affect the hypertrophy or autophagy in either muscle. Soleus showed increased autophagy signaling after hypertrophy. Overall, diabetes had no significant effect on hypertrophy or autophagy in both muscles.
BackgroundEndogenous phospholipases A2 (PLA2) play a fundamental role in inflammation, neurodegenerative diseases, apoptosis and cellular senescence. Neurotoxins with PLA2 activity are found in snake ...venoms from the Elapidae and Viperidae families. The mechanism of action of these neurotoxins have been studied using hippocampal and cerebellar neuronal cultures showing Ca2+i increase, mitochondrial depolarization and cell death. Astrocytes are rarely used as a model, despite being modulators at the synapses and responsible for homeostasis and defense in the central nervous system. Preserving the cell division ability, they can be utilized to study the cell proliferation process. In the present work cultured astrocytes and glioblastoma cells were employed to characterize the action of β-micrustoxin (previously named Mlx-9), a PLA2 isolated from Micrurus lemniscatus snake venom. The β-micrustoxin structure was determined and the cell proliferation, cell cycle phases and the regulatory proteins p53, p21 and p27 were investigated. Methodsβ-micrustoxin was characterized biochemically by a proteomic approach. Astrocytes were obtained by dissociation of pineal glands from Wistar rats; glioblastoma tumor cells were purchased from ATCC and Sigma and cultured in DMEM medium. Cell viability was evaluated by MTT assay; cell proliferation and cell cycle phases were analyzed by flow cytometry; p53, p21 and p27 proteins were studied by western blotting and immunocytochemistry. ResultsProteomic analysis revealed fragments on β-micrustoxin that aligned with a PLA2 from Micrurus lemniscatus lemniscatus previously identified as transcript ID DN112835_C3_g9_i1/m.9019. β-micrustoxin impaired the viability of astrocytes and glioblastoma tumor cells. There was a reduction in cell proliferation, an increase in G2/M phase and activation of p53, p21 and p27 proteins in astrocytes. ConclusionThese findings indicate that β-micrustoxin from Micrurus lemniscatus venom could inhibit cell proliferation through p53, p21 and p27 activation thus imposing cell cycle arrest at the checkpoint G2/M.
Although urate impaired the endothelial function, its underlying mechanism remains unknown. We hypothesized that urate impaired nitric oxide (NO) production in human umbilical vein endothelial cells ...(HUVECs) via activation of uric acid transporters (UATs).
In the present study, we studied effects of urate on NO production and eNOS protein expression in HUVEC cells in the presence and absence of urate lowering agents using molecular biological and biochemical assays.
HUVECs expressed the 4 kinds of UATs, URATv1, ABCG2, MRP4 and MCT9. Exposure to urate at 7 mg/dl for 24 h significantly reduced production of NO. Pretreatment with benzbromarone, losartan or irbesartan normalized NO production. The same exposure resulted in dephosphorylation of endothelial NO synthase (eNOS) in HUVECs. Again pretreatment with benzbromarone, losartan or irbesartan abolished this effect.
Urate reduced NO production by impaired phosphorylation of eNOS in HUVEC via activation of UATs, which could be normalized by urate lowering agents.
Hypertension is a common complication in patients with gout and/or hyperuricemia. Besides, hyperuricemia is a risk factor of gout as well as ischemic heart disease in hypertensive patients. Moreover, ...the risk of gout is modified by antihypertensive drugs. However, it remains unclear how antihypertensive agents affect uric acid metabolism.
In the present study, we investigated the uric acid metabolism in treated hypertensive patients to find out whether any of them would influence serum levels of uric acid.
751 hypertensive patients (313 men and 438 women) under antihypertensive treatment were selected. Blood pressure (BP), serum uric acid (SUA) and serum creatinine (Scr) were measured and evaluated statistically.
In patients treated with diuretics, beta-blockers and/or alpha-1 blockers SUA levels were significantly higher than in patients who were not taking these drugs. Besides, the estimated glomerular filtration rate (eGFR) in patients treated with diuretics, beta-blockers and/or alpha-1 blockers was negatively correlated with SUA level. There were gender differences in the effects of beta-blockers and alpha-1 blockers. Multiple regression analysis indicated that both diuretics and beta-blockers significantly contributed to hyperuricemia in patients with medication for hypertension.
Diuretics, beta-blockers and alpha-1 blockers reduced glomerular filtration rate and raised SUA levels. Calcium channel blockers, ACE inhibitors and angiotensin receptor blockers, including losartan, did not increase SUA levels.
TiO2 thin films with a hexagonal mesoporous structure and an anatase‐type crystalline framework are easily synthesized by a sol–gel method at low pH, using an EO–PO–EO block copolymer as template. ...While the TiO2/polymer superstructure originally has a primitive cubic structure, annealing at 150 °C affords a phase transition to hexagonal (see Figure), which persists upon template removal by calcination.
Objectives The susceptibility of clinical isolates of Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), to host-derived cationic antimicrobial peptides was investigated. ...Methods We examined the susceptibility of 190 clinical strains of methicillin-susceptible S. aureus (MSSA) and 304 strains of MRSA to two different classes of cationic antimicrobial peptides: LL-37 and human β-defensin-3 (hBD3). Out of the total 494 clinical strains, a random selection of 54 S. aureus strains was examined to establish the relationship between the net charge, or zeta potential, of each strain and its susceptibility to hBD3 or LL-37. To further confirm bacterial susceptibility to either hBD3 or LL-37, we concurrently measured: (i) percentage survival after in vitro bacterial exposure and (ii) MBCs for both MRSA and MSSA strains. Results Of the 54 randomly selected S. aureus strains, those MRSA strains resistant to LL-37 showed significantly higher zeta potentials than those susceptible to LL-37 (P < 0.05). In contrast, there was no difference in bacterial zeta potentials for MRSA strains that showed either resistance or susceptibility to hBD3. In addition, resistance to LL-37, but not to hBD3, as determined by either percentage survival or MBC, was significantly elevated in highly methicillin-resistant strains of S. aureus when compared with MSSA strains (P < 0.01). Conclusions Clinical strains of MRSA, but not MSSA, that demonstrated an increased net charge also showed elevated resistance to LL-37, but not to hBD3.
ZnO nanopillar arrays with high aspect ratios, such as the one shown in the figure, are fabricated from aqueous solutions at low temperatures using a polymer mold. The shape and dimensions of the ...nanopillars can be tuned by appropriately patterning the polymer mold. A hexagonal ZnO nanopillar array shows photonic bandgaps at visible wavelengths, as predicted by photonic band structure calculations.
Abstract
Background
In humans, uric acid is the final metabolite of adenosine triphosphate, an energy source. Xanthine oxidase (XO) contributes to urate metabolism, and XO inhibitors (XOI) suppress ...the production of uric acid and could store ATP. However, recent studies showed that discontinuation of XOI may lead to ATP depletion and increased death as a withdrawal syndrome. We examined whether the XOI withdrawal syndrome actually occurs.
Methods
This study retrospectively analyzed the Japanese Registry Of All cardiac and vascular Diseases (JROAD) database, which included 8,927,858 patients out of 9,825,635 data from April 2014 to March 2020, excluding 330,847 patients younger than 20 years and 566,930 patients older than 90 years. Of these, 356,405 were hospitalized patients with cardiovascular disease who were receiving uric acid-lowering drugs, and 315,388 were on XOI (41,017 were on other uric acid-lowering medications)(Fig). The XOI adherents were divided into the following four groups, and the number of deaths and mortality rates for each were identified as follows.
Results
(1) Those who were on the drug at admission and continued the drug at discharge: 219,020 cases, of which 59 deaths (0.03%). (2) 89,035 patients were discharged from the hospital on the medication they were on at the time of admission, of which 17,663 died (19.84%). (3) 7,241 patients who were not on any medication at admission (medication was given during hospitalization) and continued on medication at discharge, including 11 deaths (0.15%). (4) No medication at admission (medication was given during hospitalization) and stopped at discharge: 92 cases, of which 11 deaths (11.96%).
Continuous medication group: 226,261 cases, including (1) and (3), of which 70 deaths, (0.03%). Withdrawal group: 89,127 cases, including (2) and (4), of which 17,674 deaths (19.8%). The number of deaths in the withdrawal group was 620 times higher than that in the continuation group (p<0.001).
Conclusion
XOI withdrawal syndrome is detected in our study. However, some of the deaths in the XOI discontinuation group were due to the fact that other medications were also discontinued, which indicate impossible to determine a direct causal relationship between XOI withdrawal and death. Further studies are needed to check the relationship between XOI withdrawal and death in other algorithms.Fig. Flow-chart of the study
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