National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

National prevalence and determinants of COVID-19 vaccine hesitancy during the initial phase pandemic.

OBJECTIVE: Although previous studies have explored the causes of COVID-19 vaccine hesitancy during the pandemic, there is a lack of generality and reproducibility in these studies. Therefore, we aimed to comprehensively identify the determinants of COVID-19 vaccine hesitancy through a representative nationwide cross-sectional study conducted in South Korea. SUBJECTS AND METHODS: We used a nationwide, representative, and large-scale dataset from the 2021 Community Health Survey. By analyzing 193,495 participants, we investigated the nationwide incidence of COVID-19 vaccine hesitancy and the various causes thereof. RESULTS: The national prevalence of COVID-19 vaccine hesitancy was 5.7% (95% CI, 5.5-5.8). COVID-19 vaccine hesitancy was associated with an increased incidence of the following factors: (1) demographic factors including early-middle adulthood [vs. late; odds ratio (OR), 1.51; 95% CI, 1.38-1.65] and male sex (vs. female sex; OR, 1.08; 95% CI, 1.01-1.14); (2) physically healthy subjects; (3) lower socio-economic status (vs. high household income; OR, 1.28; 95% CI, 1.19-1.38); (4) having mental illness (vs. normal mental status; OR, 1.25; 95% CI, 1.13-1.38); and (5) unhealthy habits such as current smoking (vs. non-smoking; OR, 1.22; 95% CI, 1.13-1.31); and insufficient physical activity (vs. sufficient; OR, 1.08; 95% CI, 1.01-1.17). Common reasons for vaccine hesitancy were concerns about side effects (41.34%), health problems (24.60%), and inability to select the type of vaccine (14.13%). CONCLUSIONS: This representative large-scale nationwide study conducted in South Korea investigated the nationwide prevalence and determinants of vaccine hesitancy. Our results provide useful public health information, especially on novel aspects of vaccination strategies, for policymakers to improve the acceptance of COVID-19 vaccines.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Detection of the mesenchymal-to-epithelial transition of invasive non-small cell lung cancer cells by their membrane undulation spectra.

A cancer cell changes its state from being epithelial- to mesenchymal-like in a dynamic manner during tumor progression. For example, it is well known that mesenchymal-to-epithelial transition (MET) is essential for cancer cells to regain the capability of seeding on and then invading secondary/tertiary regions. However, there is no fast yet reliable method for detecting this transition. Here, we showed that membrane undulation of invasive cancer cells could be used as a novel marker for MET detection, both in invasive model cell lines and repopulated circulating tumor cells (rCTCs) from non-small cell lung cancer (NSCLC) patients. Specifically, using atomic force microscopy (AFM), it was found that the surface oscillation spectra of different cancer cells, after undergoing MET, all exhibited two distinct peaks from 0.001 to 0.007 Hz that are absent in the spectra before MET. In addition, by adopting the long short-term memory (LSTM) based recurrent neural network learning algorithm, we showed that the positions of recorded membrane undulation peaks can be used to predict the occurrence of MET in invasive NSCLC cells with high accuracy (>90% for model cell lines and >80% for rCTCs when benchmarking against the conventional bio-marker vimentin). These findings demonstrate the potential of our approach in achieving rapid MET detection with a much reduced cell sample size as well as quantifying changes in the mesenchymal level of tumor cells.

Role of TGF-ß1 and C-Kit Mutations in the Development of Hepatocellular Carcinoma in Hepatitis C Virus-Infected Patients: in vitro Study.

Transforming growth factor beta (TGF-ß) acts as a tumor-suppressing cytokine in healthy tissues and non-malignant tumors. Yet, in malignancy, TGF-ß can exert the opposite effects that can promote proliferation of cancer cells. C-Kit plays a prominent role in stem cell activation and liver regeneration after injury. However, little is known about the cross-talk between TGF-ß and C-Kit and its role in the progression of hepatocellular carcinoma (HCC). Here, we studied the effect of increasing doses of TGF-ß1 on CD44+CD90+ liver stem cells (LSCs) and C-Kit gene expression in malignant and adjacent non-malignant liver tissues excised from 32 HCC patients. The percentage of LSCs in malignant tumors was two times higher compared to their counterparts from the non-malignant tissues. When treated with increasing doses of TGF-ß1, proliferation of both malignant and non-malignant LSCs was progressively suppressed, but low TGF-ß1 dose failed to suppress the growth of malignant LSCs. Moreover, C-Kit exons 9 and 11 were expressed in malignant LSCs, but not in their non-malignant counterparts. Analysis of C-Kit detected mutations in exon 9 (but not in exon 11) in some malignant liver cells resulting in the changes in the amino acid sequence and dysregulation of protein structure and function. Interestingly, in malignant liver cells, mutations in exon 9 were associated with high-viremia hepatitis C virus (HCV), and expression of this exon was not suppressed by the TGF-ß1 treatment at all doses. To our knowledge, this is the first report that mutations in the C-Kit gene in HCC patients are associated with high- viremia HCV. Our study emphasizes the need for investigation of the TGF-ß1 level and C-Kit mutations in patients with chronic HCV for HCC prevention and better therapy management.

An electro-osmotic microfluidic system to characterize cancer cell migration under confinement.

We have developed a novel electro-osmotic microfluidic system to apply precisely controlled osmolarity gradients to cancer cells in micro-channels. We observed that albeit adhesion is not required for cells to migrate in such a confined microenvironment, the migrating velocity of cells is strongly influenced by the interactions between the cells and the channel wall, with a stronger adhesion leading to diminished cell motility. Furthermore, through examining more than 20 different types of cancer cells, we found a linear positive correlation between the protein concentration of the aquaporin-4 (AQP4) and the cell migrating speed. Knockdown of AQP4 in invasive re-populated cancer stem cells reduced their migration capability down to the level that is comparable to their parental cancer cells. Interestingly, these observations can all be quantitatively explained by the osmotic engine model where the cell movement is assumed to be driven by cross-membrane ion/water transport, while adhesion acts as a frictional resistance against the cell motility. By providing versatile and controllable features in regulating and characterizing the migration capability of cells, our system may serve as a useful tool in quantifying how cell motility is influenced by different physical and biochemical factors, as well as elucidating the mechanisms behind, in the future.

qSR: a quantitative super-resolution analysis tool reveals the cell-cycle dependent organization of RNA Polymerase I in live human cells.

We present qSR, an analytical tool for the quantitative analysis of single molecule based super-resolution data. The software is created as an open-source platform integrating multiple algorithms for rigorous spatial and temporal characterizations of protein clusters in super-resolution data of living cells. First, we illustrate qSR using a sample live cell data of RNA Polymerase II (Pol II) as an example of highly dynamic sub-diffractive clusters. Then we utilize qSR to investigate the organization and dynamics of endogenous RNA Polymerase I (Pol I) in live human cells, throughout the cell cycle. Our analysis reveals a previously uncharacterized transient clustering of Pol I. Both stable and transient populations of Pol I clusters co-exist in individual living cells, and their relative fraction vary during cell cycle, in a manner correlating with global gene expression. Thus, qSR serves to facilitate the study of protein organization and dynamics with very high spatial and temporal resolutions directly in live cell.

Cadherin- and Rigidity-Dependent Growth of Lung Cancer Cells in a Partially Confined Microenvironment.

During tumor development, cancer cells constantly confront different types of extracellular barriers. However, fundamental questions like whether tumor cells will continue to grow against confinement or away from it and what key factors govern this process remain poorly understood. To address these issues, here we examined the growth dynamics of human lung epithelial carcinoma A549 cells partially confined in micrometer-sized cylindrical pores with precisely controlled wall stiffness. It was found that, after reaching confluency, the cell monolayer enclosed by a compliant wall was able to keep growing and pushing the boundary, eventually leading to a markedly enlarged pore. In contrast, a much reduced in-plane growth and elevated strain level among cells were observed when the confining wall becomes stiff. Furthermore, under such circumstance, cells switched their growth from within the monolayer to along the out-of-plane direction, resulting in cell stacking. We showed that these observations can be well explained by a simple model taking into account the deformability of the wall and the threshold stress for inhibiting cell growth. Interestingly, cadherins were found to play an important role in the proliferation and stress buildup within the cell monolayer by aggregating at cell-cell junctions. The stiff confinement led to an elevated expression level of cadherins. Furthermore, inhibition of N-cadherin resulted in a significantly suppressed cell growth under the same confining conditions.

Urinary Tissue Inhibitor of Metalloproteinase and Insulin-like Growth Factor-7 as Early Biomarkers of Delayed Graft Function After Kidney Transplantation.

BACKGROUND: Recently, urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-7 (IGFBP-7), markers for G1 cell cycle arrest, have been identified and validated in predicting the development of acute kidney injury in critically ill patients. It is unknown, however, whether these two biomarkers could predict the development of delayed graft function (DGF) after kidney transplantation (KT). METHODS: This is a single-center, prospective, observational study. We enrolled 74 patients who underwent KT between August 2013 and December 2016. Urine sample were collected immediately after the operation. The primary outcome was development of DGF as defined by need for dialysis of more than 1 session within 7 days of KT. RESULTS: Twenty-three patients (31%) were diagnosed with DGF. In univariate analysis, kidneys from expanded criteria donors, higher donor serum creatinine, lower donor estimated glomerular filtration rate, antithymoglobulin exposure, neutrophil gelatinase associated lipocalin, and urinary [TIMP-2]·[IGFBP7] were significantly different between early graft function and DGF. However, in multivariate analysis adjusting other factors, deceased donor and urinary [TIMP-2]·[IGFBP7] at 0 hours post-transplantation could predict the development of DGF. The receiver operating characteristic curve for prediction of DGF showed an area under the curve of 0.867 (sensitivity 0.86, specificity 0.71) for a cutoff value of 1.39. CONCLUSIONS: Our results indicate that urine [TIMP-2]·[IGFBP7] immediately after transplantation could be an early, predictive biomarker of DGF in kidney transplantation.

Long-term Clinical Outcomes of Kidney Re-transplantation.

BACKGROUND: Kidney re-transplantation is commonly considered to have a higher immunological risk than first kidney transplantation. Because of the organ shortage and increasing waiting lists, long-term outcomes of kidney re-transplantation are being studied. However, reports of re-transplantation outcomes are not common. We have reported our 30 years of experience with second kidney transplantations. METHODS: Of 1210 kidney transplantations between November 1982 and August 2016 performed in our hospital, 105 were second kidney transplantations (2nd KT). Living donor KT was 44; deceased donor KT was 61. RESULTS: Patient survival rates at 1, 5, and 10 years were 100%, 97.2%, and 90.7%, and graft survival rates were 97.0%, 94.6%, and 71.5%, respectively. The leading cause of graft failure in the 2nd KT was chronic rejection (60%). In addition, induction immunosuppressant, maintenance immunosuppressant, delayed graft function, and graft survival time at the 1st KT had a significant impact on graft survival time at the 2nd KT. CONCLUSIONS: Reasonable results in both patient survival and graft survival rates were found in the 2nd KT. Careful monitoring of immunologic risk is needed.

A High-Throughput Fluorometric Assay for Lipid-Protein Binding.

An increasing number of intracellular and extracellular proteins are shown to interact with membrane lipids under physiological conditions. For rapid and robust quantitative measurement of lipid-protein interaction, we developed a sensitive fluorescence quenching-based assay that is universally applicable to all proteins and lipids. The assay employs fluorescence protein (FP)-tagged proteins whose fluorescence emission intensity is decreased when they bind vesicles containing quenching lipids. This simple assay can be performed with a fluorescence plate reader or a spectrofluorometer and optimized for different proteins with various combinations of FPs and quenching lipids. The assay allows a rapid, sensitive, and accurate determination of lipid specificity and affinity for various lipid-binding proteins, and high-throughput screening of molecules that modulate their membrane binding.

Fluorescence-Based In Situ Quantitative Imaging for Cellular Lipids.

Membrane lipids are dynamic molecules and their local concentrations serve as regulatory signals for diverse biological processes. To achieve quantitative in situ imaging of various lipids, we developed a ratiometric analysis using fluorescence biosensors, each of which is composed of an engineered lipid-binding protein and a covalently attached solvatochromic fluorophore. To cover a wide range of lipid concentration, lipid-binding proteins are engineered to have variable dynamic ranges. These tunable sensors allow robust and sensitive in situ quantitative lipid imaging in mammalian cells, providing new insight into the spatiotemporal dynamics and fluctuation of key signaling lipids. The sensor strategy is also applicable to in situ quantification of multiple cellular lipids or a single lipid in the opposing leaflets of cell membranes.

Systematic review and meta-analysis of prostatic artery embolisation for lower urinary tract symptoms related to benign prostatic hyperplasia.

AIM: To evaluate the efficacy of prostatic artery embolisation (PAE) in lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH) at short- and mid-term follow-up. MATERIALS AND METHODS: The current study included 484 BPH patients from seven eligible studies. A meta-analysis was performed to determine the mean differences in parameters associated with LUTS, including the international prostate symptom score (IPSS), peak urinary flow (Qmax), post-void residual volume (PVR), quality of life score (QoL), prostate-specific antigen level (PSA), and prostatic volume (PV), between baseline and follow-up periods. RESULTS: Nearly all parameters at follow-up of 3-24 months were significantly improved compared to the baseline. Mean differences in IPSS at 3, 6, 12, and 24 months were -14.06 (95% confidence interval [CI]: -16.47 to -11.64), -12.32 (95% CI: -15.57 to -9.08), -16.41 (95% CI: -19.81 to -13.02), and -17 (95% CI: -17.91 to -16.09), respectively. In addition, mean differences of Qmax, PVR, PV, and QoL between the follow-up period and baseline were improved significantly; however, there were no significant differences in PSA at 24 months. CONCLUSION: The present data shows that PAE could improve LUTS by BPH after short- and mid-term follow-up; however, more cumulative studies for long-term follow-up and comparison with other therapeutic modalities will be needed.

Diet-induced obesity reduces the production of influenza vaccine-induced antibodies via impaired macrophage function.

Obesity is a metabolic disease characterized by low-level chronic inflammation. Obese individuals are susceptible to infection by viruses, and vaccination against these pathogens is less effective than in nonobese individuals. Here, we sought to explore the immunological environment in a mouse model of obesity induced by a high-fat diet (HFD). HFD treatment increased the body weight and epididymal fat mass. The proportion of activated B cells, T cells, and macrophages was similar between mice in the HFD group and the regular-fat diet (RFD) group. The Th1 cell subpopulation in the HFD group was increased, whereas the proportion of Treg cells was reduced compared with the RFD group. Moreover, T-cell proliferation and cytokine production did not differ between the groups when cells were stimulated with anti-CD3 and anti-CD28 antibodies in vitro. In macrophages, phagocytic activity was higher in mice fed an HFD than in those fed an RFD, but expression levels of CD86 and MHC class II antigens were similar. When macrophages were cultured in vitro, the proportion of CD86-expressing macrophages was lower in those isolated from mice in the HFD group than in those isolated from the RFD group. Furthermore, lipopolysaccharide-induced interleukin 6 (IL-6) and tumor necrosis factor alpha secretions were significantly reduced in macrophages isolated from the HFD group. In addition, influenza vaccine-induced antibodies in the HFD group diminished more rapidly than in the RFD group. These results suggest that poor functionality of macrophages during obesity might contribute to a reduction in vaccine efficacy.

Short-Term Outcomes of ABO-Incompatible Living Donor Kidney Transplantation With Uniform Protocol: Significance of Baseline Anti-ABO Titer.

Antibody-mediated rejection (AMR) is one of the major causes of poor outcomes in ABO-incompatible kidney transplantation (ABOi KT). Studies investigating AMR risk factors found that anti-ABO titer is a major issue. However, the significance of antibody titer has been debated. This retrospective study analyzed AMR risk factors in 59 patients who underwent ABOi KT between August 2010 and January 2015. We also analyzed AMR risk factors in recipients with high anti-ABO baseline titers (≥1:64 on dithiothreitol at 37°C phase or ≥1:256 on antihuman globulin phase). The 2-year patient survival rate was 95.8%, and the 2-year graft survival rate was 94.9%. Nine patients (15.3%) experienced clinical (6 of 59 [10.2%]) or subclinical (3 of 59 [5.1%]) AMR. One patient experienced graft loss from hyperacute rejection. AMR risk factor analysis revealed that baseline antibody titer was associated with incidence of AMR. In patients with high baseline titers, low doses of rituximab (200-mg single-dose), an antibody against CD20, was predictive for AMR. Six patients who received pretransplant intravenous immunoglobulin did not experience AMR even when they had high baseline antibody titers. Our results indicate that a high baseline antibody titer affected the incidence of AMR. ABOi KT candidates with high baseline titers need to undergo an intensified preconditioning protocol, including high-dose rituximab (375 mg/m(2)) and intravenous immunoglobulin.