ABSTRACT
Thrombin is a serine protease that participates in a variety of biological signaling through protease-activated receptors. Intestinal myofibroblasts play central roles in maintaining intestinal homeostasis. In this study, we found that thrombin-induced apoptosis is mediated by the calcium-mediated activation of cytosolic phospholipase A2 in the CCD-18Co cell. Thrombin reduced cell viability by inducing apoptosis and proteinase-activated receptor-1 antagonist attenuated thrombin-induced cell death. Endogenous ceramide did not affect the cell viability itself, but a ceramide-mediated pathway was involved in thrombin-induced cell death. Thrombin increased intracellular calcium levels and cytosolic phospholipase A2 activity. The ceramide synthase inhibitor Fumonisin B 1, intracellular calcium chelator BAPTA-AM, and cytosolic phospholipase A2 inhibitor AACOCF 3 inhibited thrombin-induced cell death. Thrombin stimulated arachidonic acid release and reactive oxygen species generation, which was blocked by AACOCF 3, BAPTA-AM, and the antioxidant reagent Trolox. Taken together, thrombin triggered apoptosis through calcium-mediated activation of cytosolic phospholipase A2 in intestinal myofibroblasts.
ABSTRACT
Objectives@#Rational planning and efficient management of the oral health workforce is essential for the promotion of oral health. Therefore, this study aims to analyze the distribution characteristics of dentists, using public big data. The results of this study could contribute to the development of the oral healthcare policies proposal and desirable dental services. @*Methods@#The data of dentists working in medical institutions were analyzed by type and region from 2010 to 2020 using the Korean Statistical Information Service. Python version 3.10 was employed for data analysis and visualization, and the matplotlib and seaborn libraries were used to create graphs. @*Results@#The average age of dentists working in medical institutions was 47.4 years in 2020 ― an increase by 5.3 years compared to the 2010 data. When considering different regions, the average age of dentists in major cities, including Seoul (49.7 years), was higher than in their surroundings areas (47.2-49.5 years). @*Conclusions@#A continuous increase in the average age of dentists over the past 10 years and a difference in age distribution among different regions were observed. This is probably because new dental clinics are opening predominantly in smaller cities. Therefore, institutional support for new dental clinics in these areas is necessary to promote high-quality dental healthcare within regions.Additionally, oral healthcare services to vulnerable populations should be provided through a national oral healthcare policy utilizing these local dental clinics.
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Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.
ABSTRACT
Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.
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Purpose@#This study aimed to identify ICU nurses‘experiences with patient care after death. @*Methods@#The data were collected through two focus group interviews with eight nurses who had experienced the death of patients in the ICU. Giorgi’s method of descriptive phenomenology was used to interpret the data. @*Results@#Five constituents and 14 subconstituents were extracted from the 68 units of meaning. The five constituents were as follows: respect the body as a person, consideration and support for the family, dichotomy between personal courtesy and performing tasks, overcoming the patient’s death and growing, and care after death: a unique role left to the nurse. @*Conclusion@#These findings illuminate the meaning of care after death as a continuation of person-centered care and can be used as primary data for the development of organizational, educational, and emotional support for nurses to accomplish their roles in the ICU.
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Purpose@#The surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%–98%. However, 3%–24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This singlecenter retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH. @*Methods@#The normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group. @*Results@#There were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency. @*Conclusion@#Preoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.
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P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1, and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects.The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined.Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean Cmax, AUCinf, and AUC0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL (p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL (p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL (p = 0.2678), respectively.In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects.
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Purpose@#This cross-sectional study aimed to evaluate the mediating and moderating effects of resilience in the relationship between experience of workplace bullying and its consequences among hospital nurses. @*Methods@#The participants included 187 registered nurses working in general hospitals or a tertiary hospital in Busan and Gyeongnam Province, South Korea. Data were collected from October 25-November 30, 2019, using structured questionnaires. The moderating effects were examined using stepwise hierarchical multiple regression models. Data were analyzed using the SPSS/WIN 23.0 statistical program. @*Results@#The results demonstrated that resilience had a moderating role in the relationship between experience of workplace bullying and its consequences in hospital nurses (β=.01, p=.024). However, resilience showed no mediating effect. @*Conclusion@#To prevent and control workplace bullying, as well as to minimize its negative effects, it is necessary to develop a program that can enhance the resilience of hospital nurses.
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Background@#Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. @*Methods@#A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). @*Results@#NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025);nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. @*Conclusion@#We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic.Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.
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Application of robotic surgery in the field of general surgery has been increasing. This paper is an overview of the current uses and future perspectives of robotic surgery in four major divisions—endocrine, upper gastrointestinal, hepato-biliary-pancreatic (HBP), and colorectal surgery.Current Concepts: In endocrine surgery, cosmetic advantage is the highest priority when selecting a surgical approach for thyroidectomy. Currently, the transaxillary route is the most common approach. The introduction of the single-port system could maximize the advantages of this technique. In upper gastrointestinal surgery, the use of robots has the advantage of better retrieval of lymph nodes, less bleeding, earlier discharge, and less complications than the laparoscopic approach. However, a more prospective comparative trial is required to confirm those findings. In the HBP field, the indications of robotic surgery have expanded, starting with cholecystectomy to more challenging procedures, such as donor hepatectomy and pancreaticoduodenectomy. Meticulous dissection using robots could provide benefits to patients. In colorectal surgery, robotic surgery is an excellent technical tool for minimally invasive surgeries for rectal cancers, especially in male patients with narrow, deep pelvises. However, further studies are required to confirm the impact of robotic surgery on rectal cancers.Discussion and Conclusion: Robots are used to provide optimal surgical outcomes. Investigating new technologies and innovative surgical procedures is the highly important for a surgeon in the era of minimally invasive surgery.
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RESULTS@#The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. @*CONCLUSIONS@#ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.
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Background@#Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. @*Objectives@#The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. @*Methods@#Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. @*Results@#Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. @*Conclusions@#These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.
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Objectives@#This study aimed to show a correlation between periodontal disease and hypertension. @*Methods@#This study analyzed data of 6794 adults over 19 years based on results from the Korea National Health and Nutrition Examination Survey for the period 2016-2018. Complex sample analysis and propensity score matching analysis methods were conducted to determine whether a correlation between periodontal disease and hypertension existed. @*Results@#Results of the complex sample logistic regression analysis were: OR=1.4 (95% CI:1.23-1.58). However, the result of the conditional logistic regression analysis after propensity score matching yielded no correlation between periodontitis and hypertension (OR=1.03 (95% CI:0.92-1.16)). @*Conclusions@#It is difficult to conclude that a significant correlation exists between hypertension and periodontal disease, and further studies need to be performed to assess a significant correlation.
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Objectives@#This study aimed to confirm the correlation between BMI and the prevalence of periodontal disease in adults, using data from the National Health and Nutrition Survey. @*Methods@#The data included general characteristics and oral examination results of individuals surveyed in the 7th National Health and Nutrition Survey (2016-2018). Among the variables examined, age, gender, education, income, obesity, hypertension, diabetes, high cholesterol, smoking/drinking, oral examination, and brushing habits were considered as the general characteristics of the study participants. Individuals with more than 4 mm depth of the periodontal pocket were defined as having periodontal disease. BMI was classified into underweight (BMI<18.5 kg/m2 ) and normal (18.5 kg/m2
ABSTRACT
RESULTS@#The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. @*CONCLUSIONS@#ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.
ABSTRACT
Background@#Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. @*Objectives@#The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. @*Methods@#Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. @*Results@#Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. @*Conclusions@#These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.
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Objectives@#This study aimed to show a correlation between periodontal disease and hypertension. @*Methods@#This study analyzed data of 6794 adults over 19 years based on results from the Korea National Health and Nutrition Examination Survey for the period 2016-2018. Complex sample analysis and propensity score matching analysis methods were conducted to determine whether a correlation between periodontal disease and hypertension existed. @*Results@#Results of the complex sample logistic regression analysis were: OR=1.4 (95% CI:1.23-1.58). However, the result of the conditional logistic regression analysis after propensity score matching yielded no correlation between periodontitis and hypertension (OR=1.03 (95% CI:0.92-1.16)). @*Conclusions@#It is difficult to conclude that a significant correlation exists between hypertension and periodontal disease, and further studies need to be performed to assess a significant correlation.
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Objectives@#This study aimed to confirm the correlation between BMI and the prevalence of periodontal disease in adults, using data from the National Health and Nutrition Survey. @*Methods@#The data included general characteristics and oral examination results of individuals surveyed in the 7th National Health and Nutrition Survey (2016-2018). Among the variables examined, age, gender, education, income, obesity, hypertension, diabetes, high cholesterol, smoking/drinking, oral examination, and brushing habits were considered as the general characteristics of the study participants. Individuals with more than 4 mm depth of the periodontal pocket were defined as having periodontal disease. BMI was classified into underweight (BMI<18.5 kg/m2 ) and normal (18.5 kg/m2
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Background@#Short stature is defined as a height below the 3rd percentile or more than two standard deviations below the mean for a given age, sex, and population. There have been inconsistent results regarding craniofacial morphology in short-statured children. This study aimed to analyze the differences between short-statured children with growth hormone deficiency, idiopathic short-statured children, and normal children. @*Methods@#Thirty-one short-statured children with growth hormone deficiency, 32 idiopathic short-statured children, and 32 healthy children were enrolled in this study. The measurements of their craniofacial structures from lateral cephalograms were evaluated. @*Results@#There were statistically significant differences among the three groups seven variables (anterior cranial base length, posterior cranial base length, total cranial base length, upper posterior facial height, posterior total facial height, mandibular ramus length, and overall mandibular length) in the linear measurement and five variables (saddle angle, gonial angle, mandibular plane angle, position of mandible, and maxilla versus mandible) in the angular measurement. @*Conclusion@#Compared to the control group, many linear and angular measurements of the craniofacial structures were significantly different in the two short-statured groups (p<0.05). Treatment plans by orthodontists should include these craniofacial structure characteristics.
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Background@#Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. @*Methods@#LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results. @*Results@#LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages. @*Conclusion@#LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.