The basic factor of cardiovascular diseases is atherosclerosis, which is due largely to an increase in the activity of the angiotensin-converting enzyme (ACE) in vessels. Flavonoids diminish the risk ...of cardiovascular diseases and the flavonoid taxifolin normalizes the activity of ACE. We examined the efficiency of seven flavonoids in preventing an increase in ACE activity in aorta of rats exposed to ionizing radiation. It was shown that the activity of flavones and flavonols decreases with an increase in the number of OH groups in the A and B rings, respectively. The reduction in the activity of flavonoids within the classes correlates with a decrease in their lipophilicity. Flavanonols (taxifolin) are more active than flavonols, and flavonols are more active than flavones.
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•All-halide nanocrystals phosphors embedded in a UV-polymer matrix is proposed.•Alternating stacks of red/green halide layers are controlled for best white luminescence.•Adjusted ...prismatic patterns for the red halide layer strengthen the white luminescence.•A polymer-passivation method is very effective for strong optical stability up to 120 h.
Perovskite halide nanocrystals have been actively investigated for use in white-luminescence photonic devices. Herein, a remote phosphor-layered composite consisting of all-halide red and green nanocrystals embedded in an ultraviolet (UV)-cured matrix is proposed as a facile way to create competitive white luminescence. Alternating stacks of cast halide layers with controlled concentration and thickness yielded true white luminescence characteristics when the halide layers were combined with a bottom blue chip. Specifically, the adjusted prismatic pattern for the red halide layer was found to effectively strengthen the emission of white luminescence. In particular, a phosphor-stacked structure of green and red layers with a 9-μm-pitch prismatic pattern resulted in an enhanced luminous efficacy of ∼54.4 lm W−1, which is higher than those of a non-prismatic layer or a larger pitch pattern. Encapsulating both sides of the halide layers with polydimethylsiloxane (PDMS) maintained very effectively the luminescence of the halide layers over the exposure of 300 h.
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by SFTS virus (SFTSV) infection. Despite a gradual increase of SFTS cases and high mortality in endemic ...regions, no specific viral therapy nor vaccine is available. Here, we developed a single recombinant plasmid DNA encoding SFTSV genes, Gn and Gc together with NP-NS fusion antigen, as a vaccine candidate. The viral antigens were fused with Fms-like tyrosine kinase-3 ligand (Flt3L) and IL-12 gene was incorporated into the plasmid to enhance cell-mediated immunity. Vaccination with the DNA provides complete protection of IFNAR KO mice upon lethal SFTSV challenge, whereas immunization with a plasmid without IL-12 gene resulted in partial protection. Since we failed to detect antibodies against surface glycoproteins, Gn and Gc, in the immunized mice, antigen-specific cellular immunity, as confirmed by enhanced antigen-specific T cell responses, might play major role in protection. Finally, we evaluated the degree of protective immunity provided by protein immunization of the individual glycoprotein, Gn or Gc. Although both protein antigens induced a significant level of neutralizing activity against SFTSV, Gn vaccination resulted in relatively higher neutralizing activity and better protection than Gc vaccination. However, both antigens failed to provide complete protection. Given that DNA vaccines have failed to induce sufficient immunogenicity in human trials when compared to protein vaccines, optimal combinations of DNA and protein elements, proper selection of target antigens, and incorporation of efficient adjuvant, need to be further investigated for SFTSV vaccine development.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Primary hepatocytes and various animal models have traditionally been used in liver function tests to assess the effects of nutrients. However, these approaches present several limitations such as ...time consumption, high cost, the need for facilities, and ethical issues in primary mouse hepatocytes and animal models. In this study, we constructed liver organoids from primary mouse hepatocytes (OrgPH) to replace primary hepatocytes and animal models. We isolated primary mouse hepatocytes from 6- to 10-week-old male C57BL/6J mice using the two-step collagenase method, and generated liver organoids by clustering the cells in Matrigel. To assess the hepatic function of OrgPH, we examined specific liver markers and gene expressions related to hepatic glucose, ethanol, and cholesterol metabolism. Over a 28-day culture period, liver-specific markers, including
Alb
,
Arg1
,
G6pc
, and
Cyp1a1
, increased or remained stable in the OrgPH. However, they eventually decreased in primary hepatocytes. Glucose and ethanol metabolism-related gene expression levels exhibited a similar tendency in AML12 cells and OrgPH. However, the expression levels of cholesterol metabolism-related genes displayed an opposite trend in OrgPH compared with those in AML12 cells. These results agree with those of previous studies involving
in vivo
models. In conclusion, our study indicates that OrgPH can retain liver function and mimic the hepatocytic physiology of mouse
in vivo
models. Therefore, organoids originating from primary mouse hepatocytes are potentially useful as an animal-free method for evaluating the safety and toxicity of health functional foods and a replacement for animal models.
Physical inactivity and high-fat diet, especially high saturated fat containing diet are established risk factors for breast cancer that are amenable to intervention. High-fat diet has been shown to ...induce tumor growth and metastasis by alteration of inflammation but steady exercise has anti-tumorigenic effects. However, the mechanisms underlying the effects of physical activity on high-fat diet stimulated breast cancer initiation and progression are currently unclear. In this study, we examined how the intensity of physical activity influences high fat diet-stimulated breast cancer latency and progression outcomes, and the possible mechanisms behind these effects. Five-week-old female Balb/c mice were fed either a control diet or a high-fat diet for 8 weeks, and then 4T1 mouse mammary tumor cells were inoculated into the mammary fat pads. Exercise training occurred before tumor cell injection, and tumor latency and tumor volume were measured. Mice with a high-fat diet and low-intensity exercise (HFLE) had a longer tumor latency period, slower tumor growth, and smaller tumor volume in the final tumor assessment compared with the control, high-fat diet control (HFDC), and high-fat diet with moderate-intensity exercise (HFME) groups. Steady low- and moderate-intensity exercise had no effect on cell proliferation but induced apoptosis by activating caspase-3 through the alteration of Bcl-2, Bcl-xL, and Bax expression. Furthermore, steady exercise reduced M2 macrophage polarization in breast tumor tissue, which has been linked to tumor growth. The myokine, myostatin, reduced M2 macrophage polarization through the inhibition of the JAK-STAT signaling pathway. These results suggest that steady low-intensity exercise could delay breast cancer initiation and growth and reduce tumor volume through the induction of tumor cell apoptosis and the suppression of M2 macrophage polarization.
Lower education level could be a risk factor for higher peritoneal dialysis (PD)-associated peritonitis, potentially resulting in technique failure. This study evaluated the influence of lower ...education level on the development of peritonitis, technique failure, and overall mortality.
Patients over 18 years of age who started PD at Seoul National University Hospital between 2000 and 2012 with information on the academic background were enrolled. Patients were divided into three groups: middle school or lower (academic year≤9, n = 102), high school (9<academic year≤12, n = 229), and higher than high school (academic year>12, n = 324). Outcomes were analyzed using Cox proportional hazards models and competing risk regression.
A total of 655 incident PD patients (60.9% male, age 48.4±14.1 years) were analyzed. During follow-up for 41 (interquartile range, 20-65) months, 255 patients (38.9%) experienced more than one episode of peritonitis, 138 patients (21.1%) underwent technique failure, and 78 patients (11.9%) died. After adjustment, middle school or lower education group was an independent risk factor for peritonitis (adjusted hazard ratio HR, 1.61; 95% confidence interval CI, 1.10-2.36; P = 0.015) and technique failure (adjusted HR, 1.87; 95% CI, 1.10-3.18; P = 0.038), compared with higher than high school education group. However, lower education was not associated with increased mortality either by as-treated (adjusted HR, 1.11; 95% CI, 0.53-2.33; P = 0.788) or intent-to-treat analysis (P = 0.726).
Although lower education was a significant risk factor for peritonitis and technique failure, it was not associated with increased mortality in PD patients. Comprehensive training and multidisciplinary education may overcome the lower education level in PD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The effect of an electron beam on the toxic microalgae
Cochlodinium
polykrikoides
and
Alexandrium catenella
, which are involved in the phenomenon of seawater blooming known as red tides, has been ...studied. This annual disaster causes mass intoxication and death of marine life. Electron-beam irradiation at an absorbed dose of to 1 kGy leads to inactivation of more than 2/3 of the microalgae population due to disruption of cell walls, damage to chloroplasts, and cell aggregation. Radiolysis destroys paralytic toxins, including the most dangerous of them. Because of low doses and the ease of irradiation, the electron-beam treatment of water can be a promising method for the inactivation and detoxification of phytoplankton involved in red tides.
This case report describes the successful use of a XEN gel stent for controlling intraocular pressure (IOP) in a patient who had previously undergone scleral encircling for rhegmatogenous retinal ...detachment. The patient had very limited mobile conjunctiva due to scarring caused by the earlier surgery, which limited their options for glaucoma surgery. The XEN gel stent, a minimally invasive glaucoma surgery (MIGS) procedure that does not require opening the conjunctiva, was implanted in the subconjunctival space using an ab interno approach. Postoperative blebs were imaged using anterior segment optical coherence tomography, and IOP was monitored over six months. This study found that the XEN gel stent effectively controlled the IOP, and there were no complications during or after surgery. This case report may expand the indication for the XEN gel stent, which could be considered a viable option for patients who have undergone scleral buckling and have limited mobile conjunctiva.
The newly emerging Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe respiratory infection with a high mortality rate (~35%). MERS-CoV has been a global threat due to continuous ...outbreaks in the Arabian peninsula and international spread by infected travelers since 2012. From May to July 2015, a large outbreak initiated by an infected traveler from the Arabian peninsula swept South Korea and resulted in 186 confirmed cases with 38 deaths (case fatality rate, 20.4%). Here, we show the rapid emergence and spread of a mutant MERS-CoV with reduced affinity to the human CD26 receptor during the South Korean outbreak. We isolated 13 new viral genomes from 14 infected patients treated at a hospital and found that 12 of these genomes possess a point mutation in the receptor-binding domain (RBD) of viral spike (S) protein. Specifically, 11 of these genomes have an I529T mutation in RBD, and 1 has a D510G mutation. Strikingly, both mutations result in reduced affinity of RBD to human CD26 compared to wild-type RBD, as measured by surface plasmon resonance analysis and cellular binding assay. Additionally, pseudotyped virus bearing an I529T mutation in S protein showed reduced entry into host cells compared to virus with wild-type S protein. These unexpected findings suggest that MERS-CoV adaptation during human-to-human spread may be driven by host immunological pressure such as neutralizing antibodies, resulting in reduced affinity to host receptor, and thereby impairs viral fitness and virulence, rather than positive selection for a better affinity to CD26.
Recently, a large outbreak initiated by an MERS-CoV-infected traveler from the Middle East swept South Korea and resulted in 186 confirmed cases with 38 deaths. This is the largest outbreak outside the Middle East, and it raised strong concerns about the possible emergence of MERS-CoV mutations. Here, we isolated 13 new viral genomes and found that 12 of them possess a point mutation in the receptor-binding domain of viral spike protein, resulting in reduced affinity to the human cognate receptor, CD26, compared to the wild-type virus. These unexpected findings suggest that MERS-CoV adaptation in humans may be driven by host immunological pressure.
The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after ...infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1α in these cells and the activity of p38 MAPK and c-
that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-
in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.
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