Vitis Vinifera Seed Extract Versus Micronized Purified Flavonoid Fraction for Patients with Chronic Venous Disease: A Randomized Noninferiority Trial.

BACKGROUND: Venoactive drugs (VADs) based on Vitis vinifera extract are widely used in Korea. However, studies on the clinical effects and head-to-head comparisons with other groups of VADs are limited. This trial aimed to evaluate whether Vitis vinifera seed extract was noninferior to the micronized purified flavonoid fraction (MPFF) in relieving venous symptoms and improving quality of life in patients with chronic venous disease. METHODS: In this double-blind prospective randomized trial, patients from 13 hospitals, who were diagnosed with venous incompetence by duplex ultrasound and classified as clinical class 1, 2, or 3 in the Clinical, Etiological, Anatomical, and Pathophysiological classifications were enrolled. The primary outcome was the change in the Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-20) score at 8 weeks from baseline. Secondary outcomes included changes in the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score at 4 and 8 weeks from baseline. Moreover, the change in leg circumferences was measured at 8 weeks and compared to baseline. RESULTS: In total, 303 patients were enrolled and randomly assigned to receive either Vitis vinifera seed extract (n = 154) or MPFF (n = 149). The CIVIQ-20 scores at 8 weeks were significantly reduced compared to those at baseline in both groups. No significant intergroup difference in the change of CIVIQ-20 at 8 weeks from baseline was observed (-8.31 ± 14.63 vs. -10.35 ± 14.38, P = 0.29, 95% confidence interval -1.65 to 5.72). The lower limit of the 95% confidence interval was within the predefined noninferiority margin of 6.9. Furthermore, the Aberdeen Varicose Vein Questionnaire, visual analog scale, and Venous Clinical Severity Score scores significantly decreased at 4 and 8 weeks after randomization compared with baseline in both groups. No significant differences were observed in the reduction of each score between groups. The calf circumference measured at 8 weeks was significantly reduced compared to that at baseline in patients receiving Vitis vinifera seed extract. CONCLUSIONS: Vitis vinifera seed extract was noninferior to MPFF in relieving venous symptoms and improving the quality of life in patients with chronic venous disease.

In vitro and in vivo suppression of SARS-CoV-2 replication by a modified, short, cell-penetrating peptide targeting the C-terminal domain of the viral spike protein.

Peptides are promising therapeutic agents for COVID-19 because of their specificity, easy synthesis, and ability to be fine-tuned. We previously demonstrated that a cell-permeable peptide corresponding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike C-terminal domain (CD) inhibits the interaction between viral spike and nucleocapsid proteins that results in SARS-CoV-2 replication in vitro. Here, we used docking studies to design R-t-Spike CD(D), a more potent short cell-penetrating peptide composed of all D-form amino acids and evaluated its inhibitory effect against the replication of SARS-CoV-2 S clade and other variants. R-t-Spike CD(D) was internalized into Vero cells and Calu-3 cells and suppressed the replication of SARS-CoV-2 S clade, delta variant, and omicron variant with higher potency than the original peptide. In hemizygous K18-hACE2 mice, intratracheal administration of R-t-Spike CD(D) effectively delivered the peptide to the trachea and lungs, whereas intranasal administration delivered the peptide mostly to the upper respiratory system and stomach, and a small amount to the lungs. Administration by either route reduced viral loads in mouse lungs and turbinates. Furthermore, intranasally administered R-t-Spike CD(D) mitigated pathological change in the lungs and increased the survival of mice after infection with the SARS-CoV-2 S clade or delta variant. Our data suggest that R-t-Spike CD(D) has potential as a therapeutic agent against SARS-CoV-2 infection.

Treatment Outcomes of Patients With Ruptured Abdominal Aortic Aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is a serious complication of abdominal aortic aneurysm associated with high operative mortality and morbidity rates. The present study evaluated the perioperative and long-term outcomes of Korean patients with rAAA based on national health insurance claims data. METHODS: The National Health Insurance Service (NHIS) database was searched retrospectively to identify patients with rAAA who underwent endovascular aneurysm repair (EVAR) and open surgical repair (OSR) from 2009 to 2018. Perioperative (≤ 30 days), early postoperative (≤ 3 month), and long-term (> 3 month) survival, reinterventions, and complications were assessed. RESULTS: The search identified 1,034 patients with rAAA, including 594 who underwent EVAR and 440 who underwent OSR. When the study period was divided into two, the total numbers of patients with rAAA, patients who underwent EVAR, and octogenarians were higher during the second half. The perioperative mortality rate was 29.8% in the EVAR and 35.0% in the OSR group (P = 0.028). Hartmann's procedure for bowel infarction was performed more frequently in the OSR than in the EVAR group (adjusted odds ratio, 6.28; 95% confidence interval [CI], 2.33-21.84; P = 0.001), but other complication rates did not differ significantly. All-cause mortality during the entire observation period did not differ significantly in the EVAR and OSR groups (adjusted hazard ratio, 1.17; 95% CI, 0.98-1.41; P = 0.087). Abdominal aortic aneurysm-related reintervention rate was significantly lower in the OSR group (adjusted hazard ratio, 0.31; 95% CI, 0.14-0.70; P = 0.005). CONCLUSION: Although EVAR showed somewhat superior perioperative outcomes for rAAA, the long-term outcomes of EVAR after excluding initial 3 months were significantly worse than OSR. When anatomically feasible for both treatments, the perioperative mortality risk and reasonable prospects of long-term survival should be considered in rAAA.

Trends of Blood Transfusion According to Diseases in Korea: A 10-Year Nationwide Cohort Study.

Introduction: Recent guidelines recommend restrictive red blood cell transfusion; therefore, hospitals have started introducing and implementing patient blood management programs. This is the first study to analyze changes in the trends of blood transfusions in the whole population over the past 10 years according to sex, age group, blood component, disease, and hospital type. Methods: This cohort study analyzed blood transfusion records for 10 years, from January 2009 to December 2018, using nationwide population-based data from the Korean National Health Insurance Service-Health Screening Cohort database. Results: The proportion of transfusion procedures conducted in the total population has increased constantly for 10 years. Although its proportion in the age group of 10-79 years decreased, the total number of transfusions increased significantly due to the increase in the population and proportion of transfusions in those aged 80 years or older. Furthermore, the proportion of multicomponent transfusion procedures increased in this age group, which was greater than that of transfusions. The most common disease among transfusion patients in 2009 was cancer, of which gastrointestinal (GI) cancer accounted for more than half, followed by trauma and hematologic diseases (GI cancers > trauma > other cancers > hematologic diseases). The proportion of patients with GI cancer decreased, whereas that of trauma and hematologic diseases increased over the 10 years, with trauma becoming the most common disease type in 2018 (trauma > GI cancers > hematologic diseases > other cancers). Although transfusion rates per hospitalization decreased, the total number of inpatients increased, thus increasing the number of blood transfusions in all types of hospitals. Discussion/Conclusions: The proportion of transfusion procedures in the total population increased owing to the increase in the total number of transfusions in patients aged 80 years or older. The proportion of patients with trauma and hematologic diseases has also increased. Moreover, the total number of inpatients has been increasing, which subsequently increases the number of blood transfusions performed. Specific management strategies targeting these groups may improve blood management.

Outbred Mice with Streptozotocin-Induced Diabetes Show Sex Differences in Glucose Metabolism.

Outbred mice (ICR) with different genotypes and phenotypes have been reported to be more suitable for scientific testing than inbred mice because they are more similar to humans. To investigate whether the sex and genetic background of the mice are important factors in the development of hyperglycemia, we used ICR mice and divided them into male, female, and ovariectomized female (FOVX) groups and treated them with streptozotocin (STZ) for five consecutive days to induce diabetes. Our results show that fasting blood glucose and hemoglobin A1c (HbA1c) levels were significantly higher in diabetes-induced males (M-DM) and ovariectomized diabetes-induced females (FOVX-DM) than in diabetes-induced females (F-DM) at 3 and 6 weeks after STZ treatment. Furthermore, the M-DM group showed the most severe glucose tolerance, followed by the FOVX-DM and F-DM groups, suggesting that ovariectomy affects glucose tolerance in female mice. The size of pancreatic islets in the M-DM and FOVX-DM groups was significantly different from that of the F-DM group. The M-DM and FOVX-DM groups had pancreatic beta-cell dysfunction 6 weeks after STZ treatment. Urocortin 3 and somatostatin inhibited insulin secretion in the M-DM and FOVX-DM groups. Overall, our results suggest that glucose metabolism in mice is dependent on sex and/or genetic background.

Risk of acute and chronic coronary syndrome in a population with periodontitis: A cohort study.

OBJECTIVE: To investigate the role of periodontitis in the risk of acute and chronic coronary syndrome with compounding factors, including sociodemographic factors and medication use. METHODS: This retrospective cohort study used nationwide, population-based data from the Korean National Health Insurance Service-Health Screening Cohort database (514,866 individuals, 40-79 years). Propensity score matching was used for analysis. Information of subjects for 12 years was included. Socioeconomic and clinical factors were recorded and analysed. RESULTS: The periodontitis group had a greater risk of overall acute coronary syndrome (hazard ratio [95% confidence interval] =1.25 [1.15, 1.35], p < .001) and non-fatal acute coronary syndrome (1.26 [1.16, 1.37], p < .001). The hazard ratio for chronic coronary syndrome was higher in patients with periodontitis (1.35 [1.25, 1.46], p < .001). The cumulative incidence of both acute and chronic coronary syndrome gradually increased, and the hazard ratios reached 1.25 and 1.35 at the 12-year follow-up, respectively. Subgroup analysis revealed that periodontitis had a significantly greater link with acute coronary syndrome incidence in males, younger adults, smokers and subjects without hypertension (p < .01) and with chronic coronary syndrome incidence in smokers, subjects without hypertension and subjects without dyslipidaemia (p < .05). CONCLUSIONS: Periodontitis is associated with an increased risk of acute and chronic coronary syndrome.

Metabolic syndrome and the risk of COVID-19 infection: A nationwide population-based case-control study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a chronic, low-grade inflammatory disease. This study aimed to investigate the impact of MetS on the risk and severity of COVID-19. METHODS AND RESULTS: We investigated a nationwide cohort with COVID-19 including all patients who underwent the test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Korea. The COVID-19 group included 4070 patients with positive SARS-CoV-2 test results, and the age- and sex-matched control group included 27,618 subjects with negative SARS-CoV-2 test results. The endpoints were SARS-CoV-2 positivity and the severity of COVID-19. The prevalence of MetS was 24.7% and 24.5% in the COVID-19 and control groups, respectively. The presence of MetS was not associated with the risk of developing COVID-19. Among the components of MetS, central obesity was associated with a higher risk of COVID-19 infection (adjusted odds ratio [aOR], 1.17; 95% confidence interval [CI], 1.06-1.28, P = 0.001). The presence of MetS was significantly associated with severe COVID-19 (aOR, 1.25; 95% CI, 0.78-2.00, P = 0.352). Among the individual components of MetS, prediabetes/diabetes mellitus was associated with a higher risk of severe COVID-19 (aOR, 1.61; 95% CI, 1.21-2.13, P = 0.001). The risk of severe COVID-19 linearly increased according to the number of metabolic components (P for trend = 0.005). CONCLUSION: In this nationwide cohort study, the individuals with MetS had a significant increase in the risk of severe COVID-19 infection. These patients, particularly those with central obesity and insulin resistance, deserve special attention amid the COVID-19 pandemic.

Hearing loss through apoptosis of the spiral ganglion neurons in apolipoprotein E knockout mice fed with a western diet.

Age-related hearing loss (ARHL) is a neurodegenerative disease associated with an aged population. ARHL is influenced by biological factors such as aging, sex difference, and atherosclerosis. The mechanisms of ARHL caused by atherosclerosis have not been previously determined in apolipoprotein E knockout (ApoE KO) male mice. To investigate the onset and cause of the hearing loss, ApoE KO male mice were treated with a western diet (ApoE KO-WD) for 16 weeks. The lipid profile, atherosclerotic plaques throughout the aorta, and auditory brainstem response (ABR) thresholds were measured in the ApoE KO-WD male mice. The expression of S100 calcium-binding protein B (S100B), a neuronal damage biomarker, was also observed. Reactive oxygen species (ROS) and apoptosis rates were detected in the cochlea of the ApoE KO male mice. Atherosclerotic plaques on the aorta and ABR thresholds were significantly increased in the ApoE KO-WD male mice at 24 weeks of age. ABR thresholds had a statistically significant positive correlation with the area of atherosclerotic plaques (r = 0.783, p = 0.013) in male mice at 24 weeks of age. S100B protein expression and the dihydroethidium (DHE) reaction to ROS in the cochlear spiral ganglion neurons (SGNs) were significantly increased in the ApoE KO and ApoE KO-WD male mice. Cells positive for active caspase-3 and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) in the SGNs were significantly increased in ApoE KO-WD male mice indicating an increased rate of cellular apoptosis. In conclusion, ROS in the SGNs were activated by increased S100B expression in ApoE KO-WD male mice, and this resulted in an increased apoptosis rate. Thus, hearing loss began at 16 weeks in ApoE KO-WD male mice. Our results suggest that the ApoE KO-WD male mice are a suitable animal model for studying ARHL associated with exacerbated atherosclerosis.

Community-level socioeconomic inequality in the incidence of ischemic heart disease: a nationwide cohort study.

BACKGROUND: The purpose of this study was to confirm that inequalities in community-level social economic status (SES) do actually impact the incidence of ischemic heart disease (IHD) using the Korean population-based cohort study of the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database. METHODS: This study used the NHIS-NSC database, a population-based cohort database established by the NHIS in South Korea. Community-level SES was classified into three categories, i.e. low, moderate, and high, according to the rank. The outcome measure of interest was IHD, which was defined according to the International Classification of Disease, 10th Revision (ICD-10) codes. RESULTS: In the low community-level SES group, the incidence of IHD was 3.56 per 1000 person years (cumulative incidence rate, 1.78%), and in the high community level SES group, it was 3.13 per 1000 person years (cumulative incidence rate, 1.57%). Multivariate analysis showed that the incidence of IHD was higher in the low community-level SES group (p = 0.029). The log-rank test showed that the cumulative incidence of IHD was higher in the low community level SES group than the high community-level SES group (adjusted hazard ratio, 1.16; 95% CI, 1.01-1.32). CONCLUSIONS: People living in areas with low community-level SES show an increased incidence of IHD. Therefore, intervention in active, health-risk behavior corrections at the local level will be required to reduce the incidence of IHD.

Psychological characteristics and associations between living kidney transplantation recipients and biologically related or unrelated donors.

BACKGROUND: Although recipients and donors in living kidney transplantation experience psychological distress-including depression and anxiety-during the pre-operative period, very few studies have evaluated the related psychological reactions. This study aimed to determine the characteristics and correlations of the mood states and personality of recipients and donors (genetically related and unrelated) of living kidney transplantations. METHODS: A total of 66 pairs of living donors and recipients were enrolled from April 2008 to June 2019 in this study, of whom 53 eligible pairs of living donors and recipients were included in the retrospective analysis of their psychological assessments in the pre-transplantation states. While participants' personality patterns were assessed using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), mood states were evaluated via both the State-Trait Anxiety Inventory (STAI) and The Center for Epidemiologic Studies Depression Scale (CES-D). Statistical analysis was performed using paired t-tests and Spearman's correlation analyses. RESULTS: The recipient group showed significantly higher scores for Hypochondriasis (t = - 4.49, p = .0001), Depression (t = - 3.36, p = .0015), and Hysteria (t = - 3.30, p = .0018) of MMPI-2 and CES-D (t = - 3.93, p = .0003) than the donor group. The biologically unrelated recipient group reported higher scores of Hypochondriasis (t = - 3.37, p = .003) and Depression (t = - 2.86, p = 0.0098) than the unrelated donor group. Higher scores for Hypochondriasis (t = - 3.00, p = 0.0054) and CES-D (t = - 3.53, p = .0014) were found in the related recipient group. A positive association was found for Hypomania (r = .40, p = .003) of MMPI-2, STAI-S (r = .36, p = .009), and CES-D (r = .36, p = .008) between the recipient and donor groups. CONCLUSIONS: Recipients suffered from a higher level of depression and somatic concerns than donors before living kidney transplantation. Psychological problems like depression and anxiety can occur in both living kidney transplantation donors and recipients. This study suggests that clinicians must pay attention to mood states not only in recipients but also in donors because of emotional contagion.

Silk Fibroin Promotes the Regeneration of Pancreatic ß-Cells in the C57BL/KsJ-Leprdb/db Mouse.

Diabetes mellitus is a chronic metabolic disease, and its progression leads to serious complications. Although various novel therapeutic approaches for diabetes mellitus have developed in the last three decades, its prevalence has been rising more rapidly worldwide. Silk-related materials have been used as anti-diabetic remedies in Oriental medicine and many studies have shown the effects of silk fibroin (SF) in both in vitro and in vivo models. In our previous works, we reported that hydrolyzed SF improved the survival of HIT-T15 cells under high glucose conditions and ameliorated diabetic dyslipidemia in a mouse model. However, we could not provide a precise molecular mechanism. To further evaluate the functions of hydrolyzed SF on the pancreatic ß-cell, we investigated the effects of hydrolyzed SF on the pancreatic ß-cell proliferation and regeneration in the mouse model. Hydrolyzed SF induced the expression of the proliferating cell nuclear antigen (PCNA) and reduced the apoptotic cell population in the pancreatic islets. Hydrolyzed SF treatment not only induced the expression of transcription factors involved in the pancreatic ß-cell regeneration in RT-PCR results but also increased neurogenin3 and Neuro D protein levels in the pancreas of those in the group treated with hydrolyzed SF. In line with this, hydrolyzed SF treatment generated insulin mRNA expressing small cell colonies in the pancreas. Therefore, our results suggest that the administration of hydrolyzed SF increases the pancreatic ß-cell proliferation and regeneration in C57BL/KsJ-Leprdb/db mice.

Genome and evolution of the shade-requiring medicinal herb Panax ginseng.

Panax ginseng C. A. Meyer, reputed as the king of medicinal herbs, has slow growth, long generation time, low seed production and complicated genome structure that hamper its study. Here, we unveil the genomic architecture of tetraploid P. ginseng by de novo genome assembly, representing 2.98 Gbp with 59 352 annotated genes. Resequencing data indicated that diploid Panax species diverged in association with global warming in Southern Asia, and two North American species evolved via two intercontinental migrations. Two whole genome duplications (WGD) occurred in the family Araliaceae (including Panax) after divergence with the Apiaceae, the more recent one contributing to the ability of P. ginseng to overwinter, enabling it to spread broadly through the Northern Hemisphere. Functional and evolutionary analyses suggest that production of pharmacologically important dammarane-type ginsenosides originated in Panax and are produced largely in shoot tissues and transported to roots; that newly evolved P. ginseng fatty acid desaturases increase freezing tolerance; and that unprecedented retention of chlorophyll a/b binding protein genes enables efficient photosynthesis under low light. A genome-scale metabolic network provides a holistic view of Panax ginsenoside biosynthesis. This study provides valuable resources for improving medicinal values of ginseng either through genomics-assisted breeding or metabolic engineering.

Chronic Nonatherosclerotic Occlusive Popliteal Artery Disease.

BACKGROUND: The outcomes of revascularization of nonatherosclerotic occlusive popliteal artery disease are unknown. Therefore, the objective of this study was to analyze the outcomes of recanalization of nonatherosclerotic occlusive popliteal artery disease, the results of which would be useful in creating surgical strategies for such cases. METHODS: From January 2000 to December 2015, a total of 22 patients with nonatherosclerotic occlusive popliteal artery disease underwent open surgical repair. We retrospectively analyzed the data of these patients. Thrombectomy with angioplasty on the occluded popliteal artery, graft interposition, and bypass surgery were conducted for revascularization of the affected region. We analyzed the overall primary patency rate, type of graft, and surgical approach. Furthermore, we compared the primary patency rate after surgical treatment. RESULTS: Of 22 patients, 3 (13.6%) had cystic adventitial disease, 16 (72.7%) had popliteal artery entrapment syndrome, and 3 (13.6%) were diagnosed as having thromboangiitis obliterans. Five patients (22.7%) underwent thrombectomy with patch angioplasty, 8 (36.3%) underwent bypass surgery, and 9 (40.9%) underwent graft interposition of the popliteal artery. All graft interpositions and thrombectomies with patch angioplasty were performed through a posterior approach, whereas all bypass surgeries were performed through a medial approach except in 1 case. The mean follow-up period was 54.95 ± 42.99 months. The overall primary patency rate at 1, 3, and 10 years was 100%, 86.9%, and 69.5%, respectively. In the bypass group, the primary patency rate at 1, 3, and 10 years was 100%, 66.7%, and 44.4%, respectively. In the other groups, the primary patency rate was 100% during the follow-up period. The difference in primary patency rate was statistically significant (P ≤ 0.05). CONCLUSIONS: The result of surgical treatment for nonatherosclerotic occlusive popliteal artery disease was better than that of atherosclerotic popliteal artery disease. Direct popliteal artery reconstruction, such as graft interposition or thrombectomy with patch angioplasty, showed better short- and long-term patency than did bypass surgery.

Intra-cardiac Embolism of a Large Bone Cement Material after Percutaneous Vertebroplasty Removed through a Combination of an Endovascular Procedure and an Inferior Vena Cava Exploration: a Case Report.

Percutaneous vertebroplasty (PVP) is a minimally invasive surgical treatment for patients with osteoporotic vertebral compression fracture (OVCF) and can rapidly alleviate pain, improve mobility, and stabilize the vertebrae. However, it has the potential to cause complications such as cement embolism. A 55-year-old female presented with pain in the lumbar region as a chief complaint. PVP was performed after diagnosis of acute OVCFs at L4 and L5. No abnormal symptoms were reported after surgery, but a large cement embolism was observed in her right atrium and ventricle. After discussion in a multi-disciplinary team, the large cement embolism was successfully removed by a combination of endovascular procedure and an inferior vena cava exploration. Surgeons must consider the possibility of intra-cardiac cement embolism after PVP. A hybrid approach of an endovascular procedure and a vascular surgery may be a reasonable treatment option to minimize the surgical procedure in cases of a large intra-cardiac cement embolism.

Causes of Failure during the Management Process from Identification of Brain-Dead Potential Organ Donors to Actual Donation in Korea: a 5-Year Data Analysis (2012-2016).

BACKGROUND: This retrospective study analyzed the causes of failure in the management process from the identification of brain-dead potential organ donors to actual donation in Korea over the past 5 years. METHODS: Data of 8,120 potential brain deaths reported to the Korea Organ Donation Agency were used, including information received at the time of reporting, donation suitability evaluation performed by the coordinator after the report, and data obtained from interviews of hospital medical staff and the donor's family. RESULTS: From January 2012 to December 2016, the total number of brain-dead potential organ donors in Korea was 8,120, of which 2,348 (28.9%) underwent organ procurement surgery with designated recipients. While the number of transplant donors has increased over time, the ratio of transplant donors to medically suitable brain-dead donors has decreased. The common causes of donation failure included donation refusal (27.6%), non-brain death (15.5%), and incompatible donation (11.6%); 104 potential donors (7.8%) were unable to donate their organs because they were not pronounced brain dead. CONCLUSION: The rate of successful organ donation may be increased by analyzing the major causes of failure in the brain-dead organ donation management process and engaging in various efforts to prevent such failures.

Improving glycemic control in model mice with type 2 diabetes by increasing superoxide dismutase (SOD) activity using silk fibroin hydrolysate (SFH).

Islet cell dysfunction in type 2 diabetes is primarily attributed to the increased apoptosis of pancreatic beta cells. Silk fibroin hydrolysate (SFH) has an effect on blood in type 2 diabetes model mice (C57BL/KsJ-db/db). However, its exact mechanism is unknown. The type 2 diabetes model mice were randomly divided into non-diabetic mice (ND), diabetic mice (DB), and diabetic mice treated with silk fibroin hydrolysate (DB-SFH). The results showed that SFH significantly decreased fasting blood glucose and hemoglobin A1c (HbA1c). The oral glucose tolerance and insulin tolerance were significantly improved in the DB-SFH group. The DB-SFH group exhibited increased superoxide dismutase (SOD) activity in the plasma, as well as increased Mn-SOD and CuZn-SOD activities in the pancreatic islets. Furthermore, the pancreatic islet cells' death was decreased in the DB-SFH group. In the DB-SFH group, the protein expression of caspase-3 was significantly decreased compared with the DB group. The expression of the Nkx6.1 and Pdx1 proteins were increased in the DB-SFH group. The results suggest that SFH prevents the degeneration of pancreatic islets via increasing SOD while hyperglycemia is alleviated by maintaining beta cell mass in type 2 diabetes model mice.

Comparison of N-methyl-D-aspartate receptor subunit 1 and 4-hydroxynonenal in the hippocampus of natural and chemical-induced aging accelerated mice.

In this study, we compared N-methyl-D-aspartate receptor type 1 (NMDAR1) and 4-hydroxynonenal (4-HNE) in the hippocampus of D-galactose (D-gal)-induced and naturally aging models of mice. These markers represent general phenotypes in aging, and they allowed us to examine the possibility of D-gal as a chemical model agent for aging. We observed an age-dependent reduction of NMDAR1 and an increase in 4-HNE in the dentate gyrus, CA1, and CA3 regions of the hippocampus via immunohistochemistry and western blot analyses. In the D-gal-induced chemical aging model, we observed similar changes in NMDAR1 and 4-HNE although the degree of reduction/increase in NMDAR1/4-HNE was not as severe as that in the naturally aged mice. These results suggest that the D-gal-induced aging model is comparable to naturally aged mice and may be useful for studies of the aging hippocampus.

Role of PTEN-Induced Protein Kinase 1 as a Mitochondrial Dysfunction Regulator in Cardiovascular Disease Pathogenesis.

Cardiovascular disease (CVD) remains a global health challenge, primarily due to atherosclerosis, which leads to conditions such as coronary artery disease, cerebrovascular disease, and peripheral arterial disease. Mitochondrial dysfunction initiates endothelial dysfunction, a key contributor to CVD pathogenesis, as well as triggers the accumulation of reactive oxygen species (ROS), energy stress, and cell death in endothelial cells, which are crucial for atherosclerosis development. This review explores the role of PTEN-induced protein kinase 1 (PINK1) in mitochondrial quality control, focusing on its significance in cardiovascular health. PINK1 plays a pivotal role in mitophagy (selective removal of damaged mitochondria), contributing to the prevention of CVD progression. PINK1-mediated mitophagy also affects the maintenance of cardiomyocyte homeostasis in ischemic heart disease, thus mitigating mitochondrial dysfunction and oxidative stress, as well as regulates endothelial health in atherosclerosis through influencing ROS levels and inflammatory response. We also investigated the role of PINK1 in vascular smooth muscle cells, emphasizing on its role in apoptosis and atherosclerosis. Dysfunctional mitophagy in these cells accelerates cellular senescence and contributes to adverse effects including plaque rupture and inflammation. Mitophagy has also been explored as a potential therapeutic target for vascular calcification, a representative lesion in atherosclerosis, with a focus on lactate-induced mechanisms. Finally, we highlight the current research and clinical trials targeting mitophagy as a therapeutic avenue for CVD.

Computed tomography-based automated measurement of abdominal aortic aneurysm using semantic segmentation with active learning.

Accurate measurement of abdominal aortic aneurysm is essential for selecting suitable stent-grafts to avoid complications of endovascular aneurysm repair. However, the conventional image-based measurements are inaccurate and time-consuming. We introduce the automated workflow including semantic segmentation with active learning (AL) and measurement using an application programming interface of computer-aided design. 300 patients underwent CT scans, and semantic segmentation for aorta, thrombus, calcification, and vessels was performed in 60-300 cases with AL across five stages using UNETR, SwinUNETR, and nnU-Net consisted of 2D, 3D U-Net, 2D-3D U-Net ensemble, and cascaded 3D U-Net. 7 clinical landmarks were automatically measured for 96 patients. In AL stage 5, 3D U-Net achieved the highest dice similarity coefficient (DSC) with statistically significant differences (p < 0.01) except from the 2D-3D U-Net ensemble and cascade 3D U-Net. SwinUNETR excelled in 95% Hausdorff distance (HD95) with significant differences (p < 0.01) except from UNETR and 3D U-Net. DSC of aorta and calcification were saturated at stage 1 and 4, whereas thrombus and vessels were continuously improved at stage 5. The segmentation time between the manual and AL-corrected segmentation using the best model (3D U-Net) was reduced to 9.51 ± 1.02, 2.09 ± 1.06, 1.07 ± 1.10, and 1.07 ± 0.97 min for the aorta, thrombus, calcification, and vessels, respectively (p < 0.001). All measurement and tortuosity ratio measured - 1.71 ± 6.53 mm and - 0.15 ± 0.25. We developed an automated workflow with semantic segmentation and measurement, demonstrating its efficiency compared to conventional methods.

Endotension Following Endovascular Aneurysm Repair: Retrospective Review of Treatment and Clinical Outcome.

Purpose: : Endotension is a rare late complication characterized by an increase in sac size without any type of endoleak following endovascular aortic aneurysm repair (EVAR). Due to its rarity, few studies have demonstrated the mechanism behind and the management of endotension. In this study, we aimed to better understand the treatment and the long-term outcome of endotension in a single-center cohort. Materials and Methods: : This study was designed for a retrospective review of the patients diagnosed with endotension between January 2006 and December 2017. The study patients were categorized into two groups (primary versus secondary) based on the presence of any type of endoleak before the diagnosis of endotension. We collected data related to endotension treatment, intraoperative findings, and long-term outcomes. Results: : In a cohort of 15 patients diagnosed with endotension following EVAR, eight were classified into the primary endotension (PE) group without prior endoleak, and seven exhibited secondary endotension (SE). Among the eight PE patients, endovascular intervention for a preemptive purpose was conducted in six patients; however, three (50%) showed continuous sac expansion and finally received open conversion. Overall, eight patients (five in PE and three in SE) underwent open conversion, and one (12.5%) presented with an undetected endoleak during the operative findings. Postoperative morbidity was observed in three patients with no operative mortality. Conclusion: : Endotension can be managed initially through simple observation for changes on serial images, along with preemptive endovascular intervention. However, surgical intervention should be considered for patients with specific indications including continuous aneurysm sac enlargement, presence of symptoms, suspicions of migration of stent-graft with endoleak, and infection.