Parkinson’s disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus Mirabilis(P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

Background: Ergothioneine (EGT) is a natural amino acid derivative in various animal organs and is a bioactive compound recognized as a food and medicine. Objectives: This study examined the effects of EGT supplementation during the in vitro maturation (IVM) period on porcine oocyte maturation and subsequent embryonic development competence after in vitro fertilization (IVF). Methods: Each EGT concentration (0, 10, 50, and 100 µM) was supplemented in the maturation medium during IVM. After IVM, nuclear maturation, intracellular glutathione (GSH), and reactive oxygen species (ROS) levels of oocytes were investigated. In addition, the genes related to cumulus function and antioxidant pathways in oocytes or cumulus cells were investigated. Finally, this study examined whether EGT could affect embryonic development after IVF. Results: After IVM, the EGT supplementation group showed significantly higher intracellular GSH levels and significantly lower intracellular ROS levels than the control group. Moreover, the expression levels of hyaluronan synthase 2 and Connexin 43 were significantly higher in the 10 µM EGT group than in the control group. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) were significantly higher in the oocytes of the 10 µM EGT group than in the control group. In the assessment of subsequent embryonic development after IVF, the 10 µM EGT treatment group improved the cleavage and blastocyst rate significantly than the control group. Conclusions Supplementation of EGT improved oocyte maturation and embryonic development by reducing oxidative stress in IVM oocytes.

The efficiency of somatic cell nuclear transfer (NT) in pigs is low and requires enhancement. We identified the most efficient method for zona pellucida (ZP) removal and blastomere aggregation in pigs and investigated whether the aggregation of NT and parthenogenetic activation (PA) of blastomeres could reduce embryonic apoptosis and improve the quality of NT-derived embryos by investigating. Embryonic developmental competence after ZP removal using acid Tyrode's solution or protease (pronase E). The embryonic developmental potential of NT-derived blastomeres was also investigated using well-of-the-well or phytohemagglutinin-L. We analyzed apoptosis in aggregate-derived blastocysts. The aggregation rate of protease-treated embryos was lower than that of Tyrode’s solution-treated embryos (69.2% vs. 88.3%). No significant difference was observed between phytohemagglutinin-L and well-of-the-well (35.7%–38.5%). However, 2P1N showed a higher number of blastocysts compared to 3N (73.8% vs. 24.3%) and an increased blastocyst diameter compared to the control and 1P2N (274 μm vs. 230–234 μm). In blastomeres aggregated using phytohemagglutinin-L, the apoptotic cell ratio was significantly higher in 1P2N and 3N than in 3P (5.91%–6.46% vs. 2.94%, respectively). Our results indicate that aggregation of one NT embryo with two PA embryos improved the rate of blastocysts with increased blastocyst diameter.

Purpose: The purpose of this longitudinal study was to identify the relationship between the readiness for hospital discharge and self-care changes in an early stage of liver transplantation after discharge. Methods: Data of 75 liver transplant recipients within one year of surgery from a transplantation center from May 2019 to May 2020 were collected for this study. Their readiness for discharge was measured before discharge. Self-care after liver transplantation was evaluated at one week, one month, and three months of discharge at outpatient visits. Linear mixed model was used to evaluate the statistical relationship. Results: The readiness for hospital discharge was significantly higher when the caregiver was a spouse (p = .027), with fewer post-transplantation days (p = .027), absence of acute rejection (p = .004), or high self-efficacy (p < .001). As a result of the linear mixed model analysis, the higher the discharge readiness score, the higher the self-care score (β = 0.29, p < .001). However, after three months, their self-care had decreased regardless of their level of readiness for hospital discharge compared to one week after discharge. Conclusion Improving the readiness before discharge is essential to enhance self-care. Also, active intervention at 3 months of discharge should be performed to check and promote their long-term self-care.

Objective: This study aimed to investigate the blood-brain barrier (BBB) disruption in mild traumatic brain injury (mTBI) patients with post-concussion syndrome (PCS) using dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging and automatic whole brain segmentation. Materials and Methods: Forty-two consecutive mTBI patients with PCS who had undergone post-traumatic MR imaging, including DCE MR imaging, between October 2016 and April 2018, and 29 controls with DCE MR imaging were included in this retrospective study. After performing three-dimensional T1-based brain segmentation with FreeSurfer software (Laboratory for Computational Neuroimaging), the mean Ktrans and vp from DCE MR imaging (derived using the Patlak model and extended Tofts and Kermode model) were analyzed in the bilateral cerebral/cerebellar cortex, bilateral cerebral/cerebellar white matter (WM), and brainstem. Ktrans values of the mTBI patients and controls were calculated using both models to identify the model that better reflected the increased permeability owing to mTBI (tendency toward higher Ktrans values in mTBI patients than in controls). The Mann-Whitney U test and Spearman rank correlation test were performed to compare the mean Ktrans and vp between the two groups and correlate Ktrans and vp with neuropsychological tests for mTBI patients. Results: Increased permeability owing to mTBI was observed in the Patlak model but not in the extended Tofts and Kermode model. In the Patlak model, the mean Ktrans in the bilateral cerebral cortex was significantly higher in mTBI patients than in controls (p = 0.042). The mean vp values in the bilateral cerebellar WM and brainstem were significantly lower in mTBI patients than in controls (p = 0.009 and p = 0.011, respectively). The mean Ktrans of the bilateral cerebral cortex was significantly higher in patients with atypical performance in the auditory continuous performance test (commission errors) than in average or good performers (p = 0.041). Conclusion BBB disruption, as reflected by the increased Ktrans and decreased vp values from the Patlak model, was observed throughout the bilateral cerebral cortex, bilateral cerebellar WM, and brainstem in mTBI patients with PCS.

OBJECTIVES: In this study the relationship between neighborhood deprivation and the unmet health care needs of elderly individuals (≥ 65 years) was examined. Some previous studies suggested that neighborhood characteristics affect access to health care, yet research on the unmet needs of older individuals is limited. METHODS: Multilevel logistic regression analysis was used to assess the relationship of neighborhood-level factors with unmet health care needs due to costs, adjusting for individual-level factors, in individuals ≥ 65 years in the 2017 Korean Community Health Survey (n = 63,388). RESULTS: There were 2.6% of elderly individuals who experienced unmet health care needs due to costs. Following adjustment for individual and neighborhood characteristics, the neighborhood deprivation in urban areas was found to have an inverse association with unmet needs (odds ratio = 0.50; 95% confidence interval = 0.24–1.06) for the most deprived quartile versus the least deprived quartile). However, in rural areas neighborhood deprivation was not a significant variable. Among the individual-level variables, household income was one of the strongest correlates with unmet needs in both urban and rural areas. CONCLUSION: The present findings suggest that targeted policy interventions reflecting both neighborhood and individual characteristics, should be implemented to reduce the unmet health care needs of elderly individuals.
Aged ; Delivery of Health Care ; Family Characteristics ; Health Services Accessibility ; Health Surveys ; Humans ; Korea ; Logistic Models ; Multilevel Analysis ; Residence Characteristics

Intestinal entrapment between two vertebral bodies is very rare. In all previous cases, it occurred by major trauma. However, the bowel entrapment between two vertebral bodies without trauma has never been reported, not to mention as the cause of lower extremity radicular pain. We describe the case of an 82-year-old female patient with right lower extremity radicular pain without recent trauma history. The patient was diagnosed sigmoid colon entrapment between the L5 and S1 vertebrae by lumbar spinal computerized tomography and magnetic resonance imaging, and showed improvement in radicular pain after manual reduction of interpositioned colon during surgery. Intestinal entrapment between two vertebrae without trauma is caused by degenerative and vacuum changes of the intervertebral disc combined with the anterior longitudinal ligament injury.
Aged, 80 and over ; Colon ; Colon, Sigmoid* ; Female ; Humans ; Intervertebral Disc ; Longitudinal Ligaments ; Lower Extremity* ; Magnetic Resonance Imaging ; Radiculopathy ; Spine* ; Vacuum

BACKGROUND: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. METHODS: Balb/c (H-2(d)) mice were fed with dendritic cell line, DC2.4 (H-2(b)) every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. RESULTS: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-gamma, IL-5, and TNF-alpha. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. CONCLUSION: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.
Animals ; Cell Proliferation ; Cytokines ; Dendritic Cells ; Ear ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunization ; Interleukin-5 ; Lymphocyte Culture Test, Mixed ; Mice ; Plasmids ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Veins

BACKGROUND: A co-inhibitory molecule, B7-H4, is believed to negatively regulate T cell immunity by suppressing T cell proliferation and inhibiting cytokine production. However, the mechanism behind B7-H4-mediated tolerance remains unclear. METHODS: Balb/c (H-2(d)) mice were fed with dendritic cell line, DC2.4 (H-2(b)) every day for 10 days. Meantime, mice were hydrodynamically injected with recombinant plasmid expressing B7-H4 fusion protein (B7-H4.hFc) or hFc via tail vein. One day after last feeding, mice were immunized with allogeneic B6 spleen cells. 14 days following immunization, mice were challenged with B6 spleen cells to ear back and the ear swelling was determined the next day. Subsequently, a mixed lymphocyte reaction (MLR) was also performed and cytokines profiles from the reaction were examined by sandwich ELISA. Frequency of immunosuppressive cell population was assayed with flow cytometry and mRNA for FoxP3 was determined by RT-PCR. RESULTS: Tolerant mice given plasmid expressing B7-H4.hFc showed a significant reduction in ear swelling compared to control mice. In addition, T cells from mice given B7-H4.hFc plasmid revealed a significant hyporesponsiveness of T cells against allogeneic spleen cells and showed a significant decrease in Th1 and Th2 cytokines such as IFN-gamma, IL-5, and TNF-alpha. Interestingly, flow cytometric analysis showed that the frequency of CD4+CD25+FoxP3+ Tregs in spleen was increased in tolerant mice given recombinant B7-H4.hFc plasmid compared to control group. CONCLUSION: Our results demonstrate that B7-H4 synergistically potentiates oral tolerance induced by allogeneic cells by increasing the frequency of FoxP3+ CD4+CD25+ Treg and reducing Th1 and Th2 cytokine production.
Animals ; Cell Proliferation ; Cytokines ; Dendritic Cells ; Ear ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunization ; Interleukin-5 ; Lymphocyte Culture Test, Mixed ; Mice ; Plasmids ; RNA, Messenger ; Spleen ; T-Lymphocytes ; Tumor Necrosis Factor-alpha ; Veins

OBJECTIVE: Although hemodialysis using heparin bound Hemophan (HBH-HD) has been reported to be a possible modality in patients at risk of bleeding, the efficiency and safety of HBH-HD is not certain. Therefore, we prospectively compared the safety and efficiency of HBH-HD with those of saline flushing HD (SF-HD) and HD using low dose heparin (LDH-HD) in 13 HD patients at risk of bleeding in a cross-over design. METHODS: The safety and efficiency were evaluated by measuring activated partial prothrombin time (aPTT) before and during HD, hemostasis time after needle removal, total blood compartment volume (TBCV) loss of dialyzer, urea clearance (K) and Kt/V. RESULTS: There was no difference in compression time needed to achieve hemostasis at puncture site after needle removal between HBH-HD, SF-HD and LDH-HD. During HBH-HD, there was a slight increase in aPTT at 15 min (50.6+/-4.5 sec), compared to predialysis levels (40.9+/-4.7 sec). In this cross- over study, aPTT during dialysis session was markedly higher in LDH-HD than those in HBH-HD or SF-HD (p<0.05). The loss of TBCV of the dialyzer was greater in SF-HD than HBH-HD or LDH-HD (17.4+/-1.9% vs. 12.4+/-1.4% vs. 10.1+/-1.8%). However, there was no difference in K (212.0+/-30.7 vs. 217.2+/-36.9 vs. 221.6+/- 29.5 mL/min) and Kt/V (1.22+/-0.12 vs. 1.24+/-0.16 vs. 1.26+/-0.18). CONCLUSION: We concluded that the safety and efficiency of HBH-HD are not different compared to SF-HD or LDH-HD and HBH-HD could an alternative hemodialysis method in patients at risk of bleeding.
Anticoagulants ; Cross-Over Studies ; Dialysis ; Flushing* ; Hemorrhage* ; Hemostasis ; Heparin* ; Humans ; Needles ; Prospective Studies ; Prothrombin Time ; Punctures ; Renal Dialysis* ; Urea