Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages.

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.

Direct Injection of Hydrogels Embedding Gold Nanoparticles for Local Therapy after Spinal Cord Injury.

In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.

Therapeutic Potential of Tauroursodeoxycholic Acid for the Treatment of Osteoporosis.

Tauroursodeoxycholic acid (TUDCA) is a US FDA-approved hydrophilic bile acid for the treatment of chronic cholestatic liver disease. In the present study, we investigate the effects of TUDCA on the proliferation and differentiation of osteoblasts and its therapeutic effect on a mice model of osteoporosis. Following treatment with different concentrations of TUDCA, cell viability, differentiation, and mineralization were measured. Three-month-old female C57BL/6 mice were randomly divided into three groups (n = 8 mice per group): (i) normal mice as the control group, (ii) ovariectomy (OVX) group (receiving phosphate-buffered saline (PBS) treatment every other day for 4 weeks), and (iii) OVX group with TUDCA (receiving TUDCA treatment every other day for 4 weeks starting 6 weeks after OVX). At 11 weeks post-surgery, serum levels of procollagen type I N-terminal propeptides (PINP) and type I collagen crosslinked C-telopeptides (CTX) were measured, and all mice were sacrificed to examine the distal femur by micro-computed tomography (CT) scans and histology. TUDCA (100 nM, 1 µM) significantly increased the proliferation and viability of osteoblasts and osteoblast differentiation and mineralization when used in vitro. Furthermore, TUDCA neutralized the detrimental effects of methylprednisolone (methylprednisolone-induced osteoblast apoptosis). In the TUDCA treatment group the PINP level was higher and the CTX level was lower, but these levels were not significantly different compared to the PBS treatment group. Micro-CT and histology showed that the TUDCA treatment group preserved more trabecular structures in the distal femur compared to the PBS treatment group. In addition, the TUDCA treatment group increased the percentage bone volume with respect to the total bone volume, bone mineral density, and mice distal femur trabeculae compared with the PBS treatment group. Taken together, our findings suggest that TUDCA may provide a favorable effect on bones and could be used for the prevention and treatment of osteoporosis.

Intravenous flat-detector computed tomography angiography for symptomatic cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

The study evaluated the diagnostic accuracy of intravenous flat-detector computed tomography (IV FDCT) angiography in assessing hemodynamically significant cerebral vasospasm in patients with subarachnoid hemorrhage (SAH) with digital subtraction angiography (DSA) as the reference. DSA and IV FDCT were conducted concurrently in patients suspected of having symptomatic cerebral vasospasm postoperatively. The presence and severity of vasospasm were estimated according to location (proximal versus distal). Vasospasm >50% was defined as having hemodynamic significance. Vasospasms <30% were excluded from this analysis to avoid spectrum bias. Twenty-nine patients (311 vessel segments) were measured. The intra- and interobserver agreements were excellent for depicting vasospasm (k = 0.84 and 0.74, resp.). IV FDCT showed a sensitivity of 95.7%, specificity of 92.3%, positive predictive value of 93.6%, and negative predictive value of 94.7% for detecting vasospasm (>50%) with DSA as the reference. Bland-Altman plots revealed good agreement of assessing vasospasm between the two tests. The discrepancy of vasospasm severity was more noted in the distal location with high-severity. However, it was not statistically significant (Spearman's rank test; r = 0.15, P = 0.35). Therefore, IV FDCT could be a feasible noninvasive test to evaluate suspected significant vasospasm in SAH.

The Relationship between Seropositive Rheumatoid Arthritis and Congestive Heart Failure: A Nationwide Longitudinal Cohort Study in Korea.

Objectives: The aim of this nationwide longitudinal cohort study is to determine the risk of congestive heart failure (CHF) associated with a seropositive rheumatoid arthritis (RA) population in Korea. Methods: In this study, National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data from 2002 to 2003 were used. The cohort was followed up with for 12 years until December of 2015. Seropositive RA was defined as a patient prescribed with a disease-modifying anti-rheumatic drug (DMARD) among patients with the International Classification of Diseases code M05 (seropositive RA). Patients who were diagnosed before 2004 were excluded. The seropositive RA group consisted of 2765 patients, and a total of 13,825 patients were in the control group. The Kaplan-Meier method was used to calculate the 12-year CHF incidence rate for each group. A Cox proportional hazards regression analysis was used to estimate the hazard ratio of CHF. Results: The hazard ratio of CHF in the seropositive RA group was 2.41 (95% confidence interval (CI): 1.40-4.14) after adjusting for age and sex. The adjusted hazard ratio of CHF in the seropositive RA group was 2.50 (95% CI: 1.45-4.30) after adjusting for age, sex, income, and comorbidities. In females aged ≥65 and aged <65, the incidence rates in the non-hypertension, non-diabetes mellitus, and non-dyslipidemia subgroups were significantly higher in the seropositive RA group than in the control group. Conclusions: This nationwide longitudinal cohort study shows an increased risk of CHF in patients with seropositive RA.

Imaging follow-up strategy after endovascular treatment of Intracranial aneurysms: A literature review and guideline recommendations.

OBJECTIVE: Endovascular coil embolization is the primary treatment modality for intracranial aneurysms. However, its long-term durability remains of concern, with a considerable proportion of cases requiring aneurysm reopening and retreatment. Therefore, establishing optimal follow-up imaging protocols is necessary to ensure a durable occlusion. This study aimed to develop guidelines for follow-up imaging strategies after endovascular treatment of intracranial aneurysms. METHODS: A committee comprising members of the Korean Neuroendovascular Society and other relevant societies was formed. A literature review and analyses of the major published guidelines were conducted to gather evidence. A panel of 40 experts convened to achieve a consensus on the recommendations using the modified Delphi method. RESULTS: The panel members reached the following consensus: 1. Schedule the initial follow-up imaging within 3-6 months of treatment. 2. Noninvasive imaging modalities, such as three-dimensional time-of-flight magnetic resonance angiography (MRA) or contrast-enhanced MRA, are alternatives to digital subtraction angiography (DSA) during the first follow-up. 3. Schedule mid-term follow-up imaging at 1, 2, 4, and 6 years after the initial treatment. 4. If noninvasive imaging reveals unstable changes in the treated aneurysms, DSA should be considered. 5. Consider late-term follow-up imaging every 3-5 years for lifelong monitoring of patients with unstable changes or at high risk of recurrence. CONCLUSIONS: The guidelines aim to provide physicians with the information to make informed decisions and provide patients with high-quality care. However, owing to a lack of specific recommendations and scientific data, these guidelines are based on expert consensus and should be considered in conjunction with individual patient characteristics and circumstances.

Intravenous flat-detector computed tomography angiography for high-grade carotid stenosis.

AIM: The significant feature of intravenous flat-detector computed tomography (IV FDCT) angiography is its role in neurointerventional setting without patient transfer. However, few studies have addressed the accuracy of IV FDCT in estimating carotid stenosis and length. This study examined the reliability of IV FDCT in the diagnosis of high-grade carotid stenosis and stenosis length with digital subtraction angiography (DSA) as the reference. METHODS: Intravenous flat-detector CT and DSA were conducted simultaneously for 33 patients with 42 stenosed carotid arteries who were suspected of having symptomatic high-grade stenosis by carotid duplex ultrasound, magnetic resonance angiography, or CT angiography. The degree of stenosis and length discrepancy between 2 tests were recorded by 2 readers. RESULTS: The intraobserver and interobserver agreements were excellent for measuring high-grade carotid stenosis (κ = 0.87 and 0.82). Intravenous flat-detector CT had a sensitivity of 96.3%, specificity of 93.3%, and negative predictive value of 93.3% for detecting high-grade stenosis (≥70%) compared with DSA. Bland-Altman plots demonstrated excellent correlation of the degree of stenosis IV FDCT with DSA. Length discrepancy (IV FDCT - DSA, in millimeters) did not differ significantly according to degree of stenosis (Spearman rank test; r = 0.18, P = 0.26). CONCLUSIONS: Intravenous flat-detector CT can be a feasible and time-saving test for evaluating high-grade carotid stenosis and stenosis length.

Extracorporeal membrane oxygenation for acute life-threatening neurogenic pulmonary edema following rupture of an intracranial aneurysm.

Neurogenic pulmonary edema (NPE) leading to cardiopulmonary dysfunction is a potentially life-threatening complication in patients with central nervous system lesions. This case report describes a 28-yr woman with life-threatening fulminant NPE, which was refractory to conventional respiratory treatment, following the rupture of an aneurysm. She was treated successfully with extracorporeal membrane oxygenation (ECMO), although ECMO therapy is generally contraindicated in neurological injuries such as brain trauma and diseases that are likely to require surgical intervention. The success of this treatment suggests that ECMO therapy should not be withheld from patients with life-threatening fulminant NPE after subarachnoid hemorrhage.

Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study.

OBJECTIVE: The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. METHODS: From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. RESULTS: According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age <65, age >65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). CONCLUSIONS: The risk rate of IS increased in patient with pyogenic spondylitis.

Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury.

BACKGROUND: Neural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation. METHODS: siRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats. RESULTS: The knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted. CONCLUSIONS: These findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.

The Association between Parkinson's Disease and Congestive Heart Failure in Korea: A Nationwide Longitudinal Cohort Study.

The purpose of this nationwide longitudinal follow-up study is to investigate the relationship between Parkinson's disease (PD) and congestive heart failure (CHF) patients in Korea. Patient data were collected using the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. The International Classification of Diseases 10-CM code G-20 distinguished 6475 PD patients who were enrolled in the PD group. After removing 1039 patients who were not hospitalized or attended an outpatient clinic less than twice, the total number of participants was reduced to 5436 individuals. Then, 177 patients diagnosed before 1 January 2004 were removed for relevancy, leaving us with 5259 PD patients. After case-control matching was completed using 1:5 age- and gender-coordinated matching, 26,295 people were chosen as part of the control group. The Cox proportional hazards regression analysis and the Kaplan-Meier technique were used to assess the risk of CHF in patients with Parkinson's disease. After controlling for age and gender, the hazard ratio of CHF in the PD group was 5.607 (95% confidence interval (CI), 4.496-6.993). After that, the hazard ratio of CHF in the PD group was modified against for comorbid medical disorders, resulting in a value of 5.696 (95% CI, 4.566-7.107). In subgroup analysis, CHF incidence rates were significantly increased in the PD group compared to the control group (males and females; aged ≥ 65 and <65; the non-diabetes and diabetes, hypertension and non-hypertension, and dyslipidemia and non-dyslipidemia subgroups). This nationwide longitudinal study shows a higher incidence rate of CHF in PD patients.

Injection of a PMMA-doped MSC spheroid gel for the treatment of painful osteoporotic vertebral compression fractures.

We aimed to develop a biocompatible treatment to overcome the limitations of polymethyl methacrylate (PMMA) vertebroplasty for osteoporotic compression fracture patients. We synthesized an injectable hydrogel containing PMMA. Mesenchymal stem cell (MSC) spheroids were included in the injectable PMMA-doped gel (= PMMA-doped spheroid gel). In vitro, the osteogenic/anti-inflammatory effects of the embedded spheroids were investigated by the quantitative real-time polymerase chain reaction method. In vivo, we used ovariectomy (OVX)-induced osteoporotic rats with injured femurs to investigate the pain-relief effects. The OVX rats were divided into four groups according to the materials injected (non, PMMA, PMMA gel, and PMMA-spheroid gel) into the lesion. The immunofluorescence (IF) intensity levels of painful markers in dorsal root ganglia (DRG) were measured. In vitro, a volumetric ratio of the gel of 8 (gel):2 (PMMA) was non-cytotoxic for MSCs and promoted the expression of osteogenic/anti-inflammatory markers. In vivo, the values of several bone parameters in the PMMA-doped spheroid gel group showed remarkable increases compared to those in the PMMA group. In addition, the IF intensity levels of the painful markers were noticeably decreased in the PMMA-spheroid gel group. We, therefore, suggest that this treatment can be useful for osteoporotic vertebral compression fracture patients.

Intrawound Vancomycin Powder Application for Preventing Surgical Site Infection Following Cranioplasty.

OBJECTIVE: Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics. METHODS: This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated. RESULTS: Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4-333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006-0.762; adjusted OR, 0.068; 95% CI, 0.006-0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up. CONCLUSION: Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.

Telemedicine Protocols for the Management of Patients with Acute Spontaneous Intracerebral Hemorrhage in Rural and Medically Underserved Areas in Gangwon State: Recommendations for Doctors with Less Expertise at Local Emergency Rooms.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

The Relationship between Parkinson's Disease and Acute Myocardial Infarction in Korea : A Nationwide Longitudinal Cohort Study.

OBJECTIVE: The goal of the following statewide age and gender-coordinated cohort study in Korea is to find out if there is a link between acute myocardial infarction (AMI) and Parkinson's disease (PD). METHODS: Utilizing the National Health Insurance Sharing Service cohort, patient data were collected. Six thousand four hundred seventy-five individuals with PD were distinguished by utilizing the International Classification of Diseases 10 code G20 and have enrolled in the PD group. The number of participants decreased to 5259 after excluding 1039 patients who were hospitalized less than one time or who visited an outpatient clinic less than twice. Then, 26295 individuals were selected as part of the control group after case control matching was conducted through 1 : 5 age- and gender-coordinated matching. The Cox proportional hazard regression analysis and Kaplan-Meier method were utilized to analyze the likelihood of AMI in PD. RESULTS: After controlling for age and gender, the hazard ratio of AMI in the PD group was 3.603 (95% confidence interval [CI], 2.837-4.577). After that, the following hazard ratio of AMI in the PD group was modified against for co-morbid medical disorders, resulting in 3.551 (95% CI, 2.795-4.511). According to a subgroup analysis, in males and females aged <65 and aged ≥65 and in the non-diabetes and diabetes, hypertension and non-hypertension, dyslipidemia and non-dyslipidemia subgroups, the AMI incidence rates were dramatically higher in the PD group compared to that of the control. CONCLUSION: Individuals with PD have a greater chance of AMI, according to this cross-national study.

Transplantation of neuron-inducing grafts embedding positively charged gold nanoparticles for the treatment of spinal cord injury.

In this study, we aimed to investigate the recovery after traumatic spinal cord injury (SCI) by inducing cellular differentiation of transplanted neural stem cells (NSCs) into neurons. We dissociated NSCs from the spinal cords of Fisher 344 rat embryos. An injectable gel crosslinked with glycol chitosan and oxidized hyaluronate was used as a vehicle for NSC transplantation. The gel graft containing the NSC and positively charged gold nanoparticles (pGNP) was implanted into spinal cord lesions in Sprague-Dawley rats (NSC-pGNP gel group). Cellular differentiation of grafted NSCs into neurons (stained with ß-tubulin III [also called Tuj1]) was significantly increased in the NSC-pGNP gel group (***p < 0.001) compared to those of two control groups (NSC and NSC gel groups) in the SCI conditions. The NSC-pGNP gel group showed the lowest differentiation into astrocytes (stained with glial fibrillary acidic protein). Regeneration of damaged axons (stained with biotinylated dextran amines) within the lesion was two-fold higher in the NSC-pGNP gel group than that in the NSC gel group. The highest locomotor scores were also found in the NSC-pGNP gel group. These outcomes suggest that neuron-inducing pGNP gel graft embedding embryonic spinal cord-derived NSCs can be a useful type of stem cell therapy after SCI.

Chirality-Dependent Anti-Inflammatory Effect of Glutathione after Spinal Cord Injury in an Animal Model.

Neuroinflammation forms a glial scar following a spinal cord injury (SCI). The injured axon cannot regenerate across the scar, suggesting permanent paraplegia. Molecular chirality can show an entirely different bio-function by means of chiral-specific interaction. In this study, we report that d-chiral glutathione (D-GSH) suppresses the inflammatory response after SCI and leads to axon regeneration of the injured spinal cord to a greater extent than l-chiral glutathione (L-GSH). After SCI, axon regrowth in D-GSH-treated rats was significantly increased compared with that in L-GSH-treated rats (*** p < 0.001). Secondary damage and motor function were significantly improved in D-GSH-treated rats compared with those outcomes in L-GSH-treated rats (** p < 0.01). Moreover, D-GSH significantly decreased pro-inflammatory cytokines and glial fibrillary acidic protein (GFAP) via inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway compared with L-GSH (*** p < 0.001). In primary cultured macrophages, we found that D-GSH undergoes more intracellular interaction with activated macrophages than L-GSH (*** p < 0.001). These findings reveal a potential new regenerative function of chiral GSH in SCI and suggest that chiral GSH has therapeutic potential as a treatment of other diseases.

Lobeglitazone Exerts Anti-Inflammatory Effect in Lipopolysaccharide-Induced Bone-Marrow Derived Macrophages.

The purpose of this study is to elucidate the anti-inflammatory effect of lobeglitazone (LOBE) in lipopolysaccharide (LPS)-induced bone-marrow derived macrophages (BMDMs). We induced nitric oxide (NO) production and pro-inflammatory gene expression through LPS treatment in BMDMs. The changes of NO release and expression of pro-inflammatory mediators by LOBE were assessed via NO quantification assay and a real-time quantitative polymerase chain reaction (RT-qPCR), respectively. In addition, the regulatory effect of LOBE on activation of mitogen-activated protein kinase (MAPK) signaling pathway was investigated by measuring the phosphorylation state of extracellular regulatory protein (ERK) and c-Jun N-terminal kinase (JNK) proteins by Western blot. Our results show that LOBE significantly reduced LPS-induced NO production and pro-inflammatory gene expression of interleukin-1ß (IL-1ß), IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and monocyte chemoattractant protein-1 (MCP-1). Moreover, LOBE reduced phosphorylation levels of ERK and JNK of MAPK signaling pathway. In conclusion, LOBE exerts an anti-inflammatory effect in LPS-induced BMDMs by suppression of NO production and pro-inflammatory gene expression, and this effect is potentially through inhibition of the MARK signaling pathway.

Inhibitory Effects of Gold and Silver Nanoparticles on the Differentiation into Osteoclasts In Vitro.

Gold nanoparticles (GNPs) have been widely studied to inhibit differentiation into osteoclasts. However, reports of the inhibitory effects of silver nanoparticles (SNPs) during the process of differentiation into osteoclasts are rare. We compared the inhibitory effect of GNPs and SNPs during the process of differentiation into osteoclasts. Bone marrow-derived cells were differentiated into osteoclasts by the receptor activator of the nuclear factor-kappa-Β ligand (RANKL). The inhibitory effect of GNPs or SNPs during the process of differentiation into osteoclasts was investigated using tartrate-resistant acid phosphatase (TRAP) and actin ring staining. The formation of TRAP positive (+) multinuclear cells (MNCs) with the actin ring structure was most inhibited in the SNP group. In addition, the expression of specific genes related to the differentiation into osteoclasts, such as c-Fos, the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP, and Cathepsin K (CTSK) were also inhibited in the SNP groups. As a result, the levels related to differentiation into osteoclasts were consistently lower in the SNP groups than in the GNP groups. Our study suggests that SNPs can be a useful material for inhibiting differentiation into osteoclasts and they can be applied to treatments for osteoporosis patients.

Association of Parkinson's disease with ischemic stroke in Korea: A nationwide longitudinal cohort study in Korea.

OBJECTIVE: The aim of this nationwide age- and sex- matched longitudinal follow up study is to determine the risk of Parkinson's disease (PD) associated with ischemic stroke in Korea. METHODS: Patient data were collected from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). PD was identified using the International Classification of Diseases (ICD) 10-CM code G 20. In total, 6,475 patients were enrolled in the PD group from the NHISS. After subtracting 1,039 patients who underwent hospitalization less than once or those who visited an outpatient clinic less than two times, 5,259 patients who were diagnosed after January 1, 2004 ultimately participated in this study. After case-control match was done through 1:5 age- and sex- stratified matching, 26,295 individuals were chosen as control. Kaplan-Meier method and Cox proportional hazard regression analysis were performed to evaluate the risk of ischemic stroke in PD. RESULTS: The hazard ratio of ischemic stroke in the PD group was 3.848 (95% confidence interval (confidence interval [CI]): 3.14-4.70) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in PD group was 3.885 (95% CI: 3.17-4.75) after adjusting for comorbidities. According to subgroup analysis, in male and female and non-diabetes and diabetes and non-hypertension and hypertension and dyslipidemia and non-dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in the PD group than those in the control group. CONCLUSIONS: This nationwide longitudinal study suggests an increased risk of ischemic stroke in PD patients.