Trehalose is a non-reducing disaccharide with two glucose molecules linked through an α, α-1,1-glucosidic bond. Trehalose has received attention for the past few decades for its role in ...neuroprotection especially in animal models of various neurodegenerative diseases, such as Parkinson and Huntington diseases. The mechanism underlying the neuroprotective effects of trehalose remains elusive. The prevailing hypothesis is that trehalose protects neurons by inducing autophagy, thereby clearing protein aggregates. Some of the animal studies showed activation of autophagy and reduced protein aggregates after trehalose administration in neurodegenerative disease models, seemingly supporting the autophagy induction hypothesis. However, results from cell studies have been less certain; although many studies claim that trehalose induces autophagy and reduces protein aggregates, the studies have their weaknesses, failing to provide sufficient evidence for the autophagy induction theory. Furthermore, a recent study with a thorough examination of autophagy flux showed that trehalose interfered with the flux from autophagosome to autolysosome, raising controversy on the direct effects of trehalose on autophagy. This review summarizes the fundamental properties of trehalose and the studies on its effects on neurodegenerative diseases. We also discuss the controversy related to the autophagy induction theory and seek to explain how trehalose works in neuroprotection.
α-Synuclein is a crucial element in the pathogenesis of Parkinson's disease (PD) and related neurological diseases. Although numerous studies have presented potential mechanisms underlying its ...pathogenesis, the understanding of α-synuclein-mediated neurodegeneration remains far from complete. Here, we show that overexpression of α-synuclein leads to impaired DNA repair and cellular senescence. Transcriptome analysis showed that α-synuclein overexpression led to cellular senescence with activation of the p53 pathway and DNA damage responses (DDRs). Chromatin immunoprecipitation analyses using p53 and γH2AX, chromosomal markers of DNA damage, revealed that these proteins bind to promoters and regulate the expression of DDR and cellular senescence genes. Cellular marker analyses confirmed cellular senescence and the accumulation of DNA double-strand breaks. The non-homologous end joining (NHEJ) DNA repair pathway was activated in α-synuclein-overexpressing cells. However, the expression of MRE11, a key component of the DSB repair system, was reduced, suggesting that the repair pathway induction was incomplete. Neuropathological examination of α-synuclein transgenic mice showed increased levels of phospho-α-synuclein and DNA double-strand breaks, as well as markers of cellular senescence, at an early, presymptomatic stage. These results suggest that the accumulation of DNA double-strand breaks (DSBs) and cellular senescence are intermediaries of α-synuclein-induced pathogenesis in PD.
This cross-sectional, retrospective, observational study aimed to analyze the distribution and healthcare usage patterns of patients with atopic dermatitis using the 2010-2018 Health Insurance Review ...and Assessment Service data. Patients diagnosed with atopic dermatitis in Korea between January 2010 and December 2018 and registered in the Health Insurance Review and Assessment national database were identified, and 270,008 patients who used healthcare services at least once during this period were evaluated to ascertain the healthcare usage patterns and treatment methods for atopic dermatitis. The number of patients with atopic dermatitis plateaued during the study period, while the number of claims and total expenses increased by a small margin. Atopic dermatitis prevalence was the highest among patients aged <5 years (31.4%), followed by those aged 5-14 years (23.53%) and 15-24 years (15.33%). However, the prevalence in these age groups showed a decreasing trend over time. The most used Western medicine treatments were injections and oral medications involving topical corticosteroids, antihistamine agents, and oral steroids, while it was acupuncture therapy in Korean medicine. The frequency of the most frequently prescribed medication, topical corticosteroid, showed a decreasing trend over time. The findings in this study will inform healthcare policy makers and clinicians across different countries on the usage trends of Western medicine and Korean medicine treatment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Over‐release of the vasoactive peptide bradykinin (BK) due to mutation in the SERPING1 gene is the leading cause of hereditary angioedema (HAE). BK directly activates endothelial cells and ...increases vascular permeability by disrupting the endothelial barrier, leading to angioedema affecting face, lips, extremities, gastrointestinal tract, and larynx. Although various pharmacological treatment options for HAE became available during the last decade, they are presently limited and pose a major economic burden on patients. To identify additional therapeutic options for HAE, we evaluated the effect of CU06‐1004, an endothelial dysfunction blocker, on BK‐induced vascular hyperpermeability and the HAE murine model.
Methods
To investigate the effect of CU06‐1004 on BK‐induced vascular hyperpermeability in vivo, we pre‐administrated WT mice with the drug and then induced vascular leakage through intravenous injection of BK and observed vascular alternation. Then, SERPING1 deficient mice were used for a HAE murine model. For an in vitro model, the HUVEC monolayer was pre‐treated with CU06‐1004 and then stimulated with BK.
Results
Bradykinin disrupted the endothelial barrier and formed interendothelial cell gaps, leading to hyperpermeability in vivo and in vitro. However, CU06‐1004 treatment protected the endothelial barrier by suppressing Src and myosin light chain activation via BK and alleviated hyperpermeability.
Conclusion
Our study shows that CU06‐1004 oral administration significantly reduced vascular hyperpermeability in the HAE murine model by protecting the endothelial barrier function against BK stimulation. Therefore, protecting endothelium against BK with CU06‐1004 could serve as a potential prophylactic/therapeutic approach for HAE patients.
Increased vascular permeability due to BK is the leading cause of the C1‐INH‐HAE. CU06‐1004 oral administration significantly alleviated vascular hyperpermeability in C1‐INH‐HAE murine in vivo model by protecting vascular integrity. CU06‐1004 protected the endothelial barrier from BK‐induced interendothelial cell gap formation by inhibiting VE‐cadherin phosphorylation and stress fiber formation.Abbreviations: BK, bradykinin; C1‐INH, C1 esterase inhibitor; C1‐INH‐HAE, hereditary angioedema caused by C1 esterase inhibitor deficiency; CTRL, control; CU06‐1004, endothelial dysfunction blocker; EC, endothelial cell; F‐actin, filamentous actin; HMW kininogen, high‐molecular‐weight kininogen; KO, knock‐out; MLC, myosin light chain; Src, non‐receptor tyrosine kinase; VE‐cadherin, vascular endothelial cadherin; WT, wild type
Display omitted
•Microwave-assisted digestion method was developedfor elemental analysis of milk samples.•Digestion solvent consisted of6 mL of 0.1 mol L−1 HNO3 and 2 mL of 30% H2O2.•The optimized ...procedureresulted in low residual carbon content and residual acidity.•The proposed method was an excellent green analysis method by analytical Eco-Scale.•16 elements were determined in milk samples from South Korea by ICP-OES and ICP-MS.
A novel method for microwave-assisted digestion of milk samples using diluted HNO3and H2O2 with a single reaction chamber was developed for elemental analysis by ICP-based techniques. The optimal conditions for digestion were 0.25 g of sample mass, 6 mL of 0.1 molL−1HNO3and 2 mL of 30% H2O2 at 250 ℃ and 160 bar. The optimized procedure resulted in low residual carbon content and residual acidity of 260 mgL−1 and 0.06 mol L−1, respectively. The limits of detection ranged from 0.286ոg g−1(Ca) to 82.990ոg g−1(Fe). In addition, the proposed method was considered an excellent green analysis method with a final score of 87 based on the analytical Eco-Scale. Finally, the method was validated and applied to the determination of Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sb, Se, and Zn in milk samples from South Korea.
Stroke and depression are common diseases that affect quality of life (QoL). Although some recent studies have investigated the association between the two diseases, studies that examined the ...association between stroke, depression, and QoL are rare, with large-scale national-level studies lacking. We aimed to investigate the association between depression and QoL in stroke patients.
Data from the Korea National Health and Nutrition Examination Survey (KNHANES) IV-VII conducted in 2008-2018 were used, and 45,741 adults who were aged >40 years and had no missing data for stroke and depression were included in the analysis. The participants were first grouped by prevalence of stroke, and further divided by prevalence of depression.
The overall prevalence of stroke was 3.2%, and the incidence was 9% higher in men than in women. Multiple logistic regression was performed after adjusting for demographic factors, health-related factors, and disease-related factors. The results confirmed that the stroke group with depression had a lower overall health-related quality of life, measured using EQ-5D, score compared to the stroke group without depression (-0.15). Moreover, the concurrent stroke and depression treatment group had the highest OR of 7.28 (95% CI 3.28-16.2) for the anxiety/depression domain.
Depression was strongly associated with QoL in stroke patients. This association was more evident in stroke patients undergoing treatment for depression. Thus, clinical approaches that take QoL into consideration are needed for stroke patients with depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Display omitted
•Cellular senescence contributes to aging and neurodegenerative diseases.•Protein aggregates can induce cellular senescence in brain cells.•Cellular senescence can be targeted for ...therapy for neurodegenerative diseases.
Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, are characterized by several pathological features, including selective neuronal loss, aggregation of specific proteins, and chronic inflammation. Aging is the most critical risk factor of these disorders. However, the mechanism by which aging contributes to the pathogenesis of neurodegenerative diseases is not clearly understood. Cellular senescence is a cell state or fate in response to stimuli. It is typically associated with a series of changes in cellular phenotypes such as abnormal cellular metabolism and proteostasis, reactive oxygen species (ROS) production, and increased secretion of certain molecules via senescence-associated secretory phenotype (SASP). In this review, we discuss how cellular senescence contributes to brain aging and neurodegenerative diseases, and the relationship between protein aggregation and cellular senescence. Finally, we discuss the potential of senescence modifiers and senolytics in the treatment of neurodegenerative diseases.
Hypoxia‐inducible factor‐1 (HIF‐1) plays an important role in cellular responses to hypoxia, including the transcriptional activation of several genes involved in tumor angiogenesis. Melatonin, also ...known as N‐acetyl‐5‐methopxytryptamine, is produced naturally by the pineal gland and has anti‐angiogenic effects in cancer through its ability to modulate HIF‐1α activity. However, the use of melatonin as a therapeutic is limited by its low oral bioavailability and short half‐life. Here, we synthesized melatonin‐like molecules with enhanced HIF‐1α targeting activity and less toxicity and investigated their effects on tumor growth and angiogenesis, as well as the underlying molecular mechanisms. Among melatonin derivatives, N‐butyryl‐5‐methoxytryptamine (NB‐5‐MT) showed the most potent HIF‐1α targeting activity. This molecule was able to (a) reduce the expression of HIF‐1α at the protein level, (b) reduce the transcription of HIF‐1α target genes, (c) reduce reactive oxygen species (ROS) generation, (d) decrease angiogenesis in vitro and in vivo, and (e) suppress tumor size and metastasis. In addition, NB‐5‐MT showed improved anti‐angiogenic activity compared with melatonin due to its enhanced cellular uptake. NB‐5‐MT is thus a promising lead for the future development of anticancer compounds with HIF‐1α targeting activity. Given that HIF‐1α is overexpressed in the majority of human cancers, the melatonin derivative NB‐5‐MT could represent a novel potent therapeutic agent for cancer.
For the elemental determination of rice, a microwave-assisted sample preparation method employing diluted HNO3 and H2O2 under high temperature and pressure was developed in a rapid and eco-friendly ...manner. The analysis was performed using inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). At 280 °C and 160 bar, the optimal condition for microwave-assisted wet digestion in a single reaction chamber was achieved with a mixture consisting of 3 mL of 0.1 mol L−1 HNO3 and 5 mL of 30% H2O2 (0.25 g rice sample). The optimized procedure yielded a low residual acidity (RA) of 0.017 mol L−1 and low residual carbon content (RCC) of 355 mg L−1. The limits of detection (LODs) were from 0.159 (Sb) to 9.863 (Fe) μg kg−1. Additionally, the developed method received a total score of 85 on the analytical Eco-Scale, indicating an excellent green analysis method. Furthermore, the method was validated by determining 19 elements (Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Ni, P, Pb, S, Sb, Se, and Zn) in brown and white rice cultivated in South Korea.
Display omitted
•A microwave-assisted digestion method was developed for elemental analysis of rice.•The digestion solvent was optimized as 3 mL of 0.1 mol L−1 HNO3 and 5 mL of 30% H2O2.•The optimal procedure provided low residual carbon content and residual acidity.•The developed method was an excellent green analysis method by analytical Eco-Scale.•19 elements were determined in brown and white rice by ICP-MS and ICP-OES.
Understanding how doctors respond to occupational and monetary incentives in health care payment systems is important for determining the effectiveness of such systems. This study examined changes in ...doctors' behaviors in response to monetary incentives within health care payment systems in a ceteris paribus setting.
An online experiment was developed to analyze the effect of monetary incentives similar to fee-for-service (FFS) and capitation (CAP) on doctors' prescription patterns. In the first session, no monetary values were presented. In the second session conducted 1 week later, doctors were randomly assigned to one of two monetary incentive groups (FFS group: n = 25, CAP group: n = 25). In all sessions, doctors were presented with 10 cases and asked to determine the type and number of treatments.
In the first session with no monetary incentives, there was no significant difference between the FFS and CAP groups in the number of treatments. When monetary incentives were provided, doctors in the CAP group prescribed fewer treatments than the FFS group. The perceived severity of the cases did not change significantly between sessions and between groups. linear mixed-effects regression model indicated the treatment choices were influenced by monetary incentives, but not by the perceived severity of the patient's symptoms.
The monetary values incentivized the doctors' treatment choices, but not their professional evaluation of patients. Monetary values designed within health care systems influence the doctor's decisions in the form of external rewards, in addition to occupational values, and can thus be adjusted by more effective incentives.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
