Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.
Background: It is getting important to improve the oral health status of the elderly because oral health status may affect their health status of the whole body. In this respect, we aimed to explore the association of oral health status and behavior factors with self-rated health status by sex. Methods: Using the data from the 7th Korea National Health and Nutrition Examination Survey for health surveys and oral examinations (2016-2018), we analyzed a total of 3,070 people aged 65 or older (men: 1,329; women: 1,741). Our dependent variable, self-rated health status, was divided into two groups: not good (bad and very bad) and good (very good, good, and fair), whereas our independent variables of interest were oral health status and behavior factors. In addition to descriptive analysis and the Rao-Scott chi-square test, reflecting survey characteristics, we conducted hierarchical multivariable logistic regression analyses adjusted for socio-demographics and health status and behavior factors. All analyses were stratified by sex. Results: The proportion of people having 'not good' self-rated health was 36.5% in women but 24.5% in men. In a model adjusted for all covariates, the self-rated health status showed significant association with the self-rated oral health status. For example, in men, the risk of having 'not good' self-rated health was high in people having 'poor' (odds ratio [OR], 5.31; 95% confidence interval [CI], 2.34-12.03) self-rated oral health status and in those having 'fair' (OR, 4.03; 95% CI, 1.68-9.70) in comparison with those having 'good' self-rated oral health status. Dental status regarding speaking difficulty seemed to be very important in influencing self-rated health status. For instance, in women, compared to people having 'no discomfort' speaking difficulty, the risk of having 'not good' self-rated health was high in people having 'not bad' (OR, 1.60; 95% CI, 1.14-2.24) and 'discomfort' (OR, 1.79; 95% CI, 1.30-2.47) speaking difficulty. The covariates significantly associated with the risk of having 'not good' self-rated health were: physical activity, chronic disease, stress, and body mass index in both sexes; health insurance type and drinking only in men; and economic activity only in women. Conclusion: Oral health status and behavioral factors were associated with self-rated health status among the elderly, differently by sex. This suggests that public health policies toward better health in the elderly should take their oral health status and oral health behaviors into account in a sex-specific way.
Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca2+]i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca2+]i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.
Yong-Jun Cho;Jae-An Jeon;Kinal Kim;Po-Lun Feng;Steven Nutt;Sang-Eui Lee
Composites Research
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v.36
no.3
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pp.199-204
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2023
A combination of a metallic mesh and an adhesive layer of metallic particle/epoxy composite was introduced as an intermediate layer to enhance the adhesion between cold-sprayed particles and fiber-reinforced composites (FRCs). Aluminum was considered for both the metallic particles in the adhesive and the metallic mesh. To predict the mechanical characteristics of the intermediate bond layer under a high strain rate, the properties of the adhesive layer needed to be calculated or measured. Therefore, in this study, the Al particle/epoxy adhesive was homogenized by using a rule of mixture. To verify the homogenization, the penetration depth, and the thickness decrease after the cold spray deposition from the undeformed surface, was monitored with FE analysis and compared with experimental observation. The comparison displayed that the penetration depth was comparable to the diameters of one cold spray particle, and thus the homogenization approach can be reasonable for the prediction of the stress level of particulate polymer composite interlayer under a high strain rate for cold spray processing.
Purpose - Turnover Intention in the franchise industry is becoming a very important issue. This study examines the structural relationships between organizational justice, emotion, job satisfaction, and turnover intention in the franchise industry. In this model, emotion was classified into two sub-dimensions such as positive and negative emotion. Research design, data, methodology - The sample of this study collected from employees of a food-service franchise company is representative. Copies of the questionnaire along with a cover letter were delivered by a research assistant to the human resources manager or the general manager of the selected food-service franchise firms after they agreed to participate in the study. In order to increase the response rate of the respondents, a small gift was provided to the respondents who completed the questionnaire. A total of 300 questionnaires were distributed and 285 returned responses, 9 responses were not usable due to missing information. Thus, a total of 276 responses were used using structural equation modeling with Smartpls 3.0. Results - The results showed that organizational justice had positive significant effects on positive emotion and job satisfaction. Job satisfaction had negative a significant effect on turnover intention. And negative emotion had positive significant effect on turnover intention. Conclusions - The results of this study provide some implications. If employees feel that the franchise headquarters is fair about the methods and procedures of decision making, resource allocation, information sharing, etc., it means that employees feel better. If the franchise's decision-making processes and methods and results are transparently disclosed and processed in accordance with the internal rules of the company, the employees will be able to fully understand and accept them. The results of this study also show that positive and negative emotions of service-based franchise employees have different effects on job attitude and organizational behavior. In particular, when negative emotions of employees are passed on to others and the results are negative, employees may feel that they are disoriented or wrong. Therefore, the franchise headquarters should try to inspire employees' sense of organizational community, and should pay attention to how to relieve the job stress and the fair distribution of work and rewards.
KSCE Journal of Civil and Environmental Engineering Research
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v.26
no.5A
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pp.861-872
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2006
The element free Galerkin method is extended by the local partition of unity method to model the cohesive cracks in two dimensional continuum. The shape function of a particle whose domain of influence is completely cut by a crack is enriched by the step enrichment function. If the domain of influence contains a crack tip inside, it is enriched by a branch enrichment function which does not have the LEFM stress singularity. The discrete equations are obtained directly from the standard Galerkin method since the enrichment is only for the displacement field, which satisfies the local partition of unity. Because only particles whose domains of influence are influenced by a crack are enriched, the system matrix is still sparse so that the increase of the computational cost is minimized. The condition for crack growth in dynamic problems is obtained from the material instability; when the acoustic tensor loses the positive definiteness, a cohesive crack is inserted to the point so as to change the continuum to a discontiuum. The crack speed is naturally obtained from the criterion. It is found that this method is more accurate and converges faster than the classical meshless methods which are based on the visibility concept. In this paper, several well-known static and dynamic problems were solved to verify the method.
Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.
Kim, Jinhee;Hwang, Taeeon;Kim, Jae-Sik;Huh, Youngki
Korean Journal of Construction Engineering and Management
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v.24
no.6
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pp.74-80
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2023
This study examines the characteristics of architectural review opinions as unstructured data, focusing on the most challenging risk for developers of small and medium-sized apartment projects in response to the increasing number of single-person households in Korea. Using multidimensional analysis methods, the study analyzes the review opinions of 25 projects in B City. Correspondence analysis and MDS (Multidimensional Scale) analysis show that, consistent with prior research, the keywords related to 'structure' and 'planning' dominate architectural review opinions in B City. While the MDS model's stress is very poor at 34.4%, correspondence analysis reveals that this is due to the characteristics of unstructured data in architectural reviews. In addition, the non-structured data analyzed in this study, such as architectural review opinions, exhibited a probability distribution with low kurtosis and high skewness, as they involved various combinations and occurrences of data depending on the discretion of the review committee members and the specific formats of different local governments. This often led to the emergence of keywords that differed significantly from commonly mentioned terms. Although the study has some limitations, it provides a foundation for future detailed analysis by identifying the characteristics of architectural review opinions as unstructured data.
Yun-seong Lee;Eun-Gyung Mun;Eun Ah Sim;Bo-Young Lee
Journal of Nutrition and Health
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v.57
no.4
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pp.389-402
/
2024
Propose: This study examined the antioxidant and anti-gastritis properties of a mixture comprising Ipomoea batatas (IB) extract and Dioscorea japonica (DJ) extract. Methods: The mixture of IB and DJ extracts was analyzed for its total flavonoid content (TFC), total polyphenol content (TPC), and radical scavenging activities. Gastric lesions were induced by treating rats with 1 mL of a solution containing 60% ethanol and 150 mM HCl. The rats were then divided into 5 groups: CON (normal control), HEC (treated with 150 mM HCl-60% ethanol and distilled water), IBE (treated with 150 mM HCl-60% ethanol and IB extract at 350 mg/kg body weight [BW]), ID30 (treated with 150 mM HCl-60% ethanol and a mixture of IB and DJ extracts in a 7:3 ratio at 350 mg/kg BW), and DJE (treated with 150 mM HCl-60% ethanol and DJ extract at 350 mg/kg BW). Results: The ID30 group exhibited significantly higher TFC, TPC, and radical scavenging activities than the groups treated with single extracts. This group also showed a notable decrease in the formation of gastric lesions and preservation of gastric wall mucus. In addition, the serum levels of the inflammatory marker tumor necrosis factor (TNF)-α were significantly lower in the ID30 group than in the HEC group. Conclusion: The antioxidants present in the ID30 mixture effectively reduced oxidative stress and reactive oxygen species, mitigating gastric mucosal irritation induced by alcohol and acid. Furthermore, the mixture inhibited gastric acid secretion and inflammatory marker expression, such as TNF-α, preventing tissue damage. These findings suggest that the ID30 mixture is a potential preventative treatment for gastritis.
Chinedu Godwin Uzomba;Uchenna Kenneth Ezemagu;Mary-Sonia Ofoegbu;Njoku Lydia;Essien Goodness;Chinedum Emelike;Uchewa Obinna;Alo Joseph Nwafor;Ejikeme Felix Mbajiorgu
Anatomy and Cell Biology
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v.57
no.3
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pp.446-458
/
2024
The study aims to compare the action of Pleurotus cornucopiae and glibenclamide on alloxan-induced diabetes and ascertain how an aqueous extract of the edible mushroom regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), oxidative stress biomarkers and renal toxicity in a diabetic male Wistar rat model. Twenty-five adult male Wistar rats were randomly grouped into five groups with five rats per. Group 1 and those in the treatment groups received normal feed and water ad libitum. Group 2 received intraperitoneal administration of alloxan monohydrate (150 mg/kg body weight). Group 3 received alloxan monohydrate and glibenclamide (5 mg/kg body weight bwt), group 4 received alloxan monohydrate plus the extract (250 mg/kg bwt) and group 5 received alloxan monohydrate plus the extract (500 mg/kg bwt). The administration of glibenclamide plus the extract was oral for 14 days. Glibenclamide and the extract lowered blood glucose level, catalase, and glutathione peroxidase activities, increased the superoxide dismutase (SOD) activity in rats with alloxan induced diabetes. The extract at 500 mg/kg bwt reduced the plasma urea and sodium concentration in the treated rats. The extract and glibenclamide could detoxify alloxan and restore its induced renal degeneration and glomeruli atrophy, intra renal hemorrhage and inflammation and oxidative biomarkers through activation of Nrf2 expression. The drug glibenclamide and P. cornucopiae have appreciable hypoglycemic activity and potential to restore the normal renal architecture in the rats, hence they offer similar curative effects. Additionally, the extract at 500 mg/kg bwt activated SOD and Nrf2 expression more than glibenclamide in rats with alloxan-induced diabetes.
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