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Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling
No full textMany bone diseases, such as osteoporosis and rheumatoid arthritis, are attributed to an increase in osteoclast number or activity; therefore, control of osteoclasts has significant clinical implications. This study shows how skullcapflavone II (SFII), a flavonoid with anti-inflammatory activity, regulates osteoclast differentiation, survival, and function. SFII inhibited osteoclastogenesis with decreased activation of MAPKs, Src, and cAMP response element-binding protein (CREB), which have been known to be redox sensitive. SFII decreased reactive oxygen species by scavenging them or activating nuclear factor-erythroid 2-related factor 2 (Nrf2), and its effects were partially reversed by hydrogen peroxide cotreatment or Nrf2 deficiency. In addition, SFII attenuated survival, migration, and bone resorption, with a decrease in the expression of integrin β3, Src, and p130 Crk-associated substrate, and the activation of RhoA and Rac1 in differentiated osteoclasts. Furthermore, SFII inhibited osteoclast formation and bone loss in an inflammation- or ovariectomy-induced osteolytic mouse model. These findings suggest that SFII inhibits osteoclastogenesis through redox regulation of MAPKs, Src, and CREB and attenuates the survival and resorption function by modulating the integrin pathway in osteoclasts. SFII has therapeutic potential in the treatment and prevention of bone diseases caused by excessive osteoclast activity.-Lee, J., Son, H. S., Lee, H. I., Lee, G.-R., Jo, Y.-J., Hong, S.-E., Kim, N., Kwon, M., Kim, N. Y., Kim, H. J., Lee, Y. J., Seo, E. K., Jeong, W. Skullcapflavone II inhibits osteoclastogenesis by regulating reactive oxygen species and attenuates the survival and resorption function of osteoclasts by modulating integrin signaling
Redox Reactivity of a Mononuclear Manganese-Oxo Complex Binding Calcium Ion and Other Redox-Inactive Metal Ions
No full textMononuclear nonheme manganese(IV)-oxo complexes binding calcium ion and other redox-inactive metal ions, [(dpaq)MnIV(O)]+-Mn+ (1-Mn+, Mn+ = Ca2+, Mg2+, Zn2+, Lu3+, Y3+, Al3+, and Sc3+) (dpaq = 2-[bis(pyridin-2-ylmethyl)]amino-N-quinolin-8-yl-acetamidate), were synthesized by reacting a hydroxomanganese(III) complex, [(dpaq)MnIII(OH)]+, with iodosylbenzene (PhIO) in the presence of redox-inactive metal ions (Mn+). The Mn(IV)-oxo complexes were characterized using various spectroscopic techniques. In reactivity studies, we observed contrasting effects of Mn+ on the reactivity of 1-Mn+ in redox reactions such as electron-transfer (ET), oxygen atom transfer (OAT), and hydrogen atom transfer (HAT) reactions. In the OAT and ET reactions, the reactivity order of 1-Mn+, such as 1-Sc3+ ≈ 1-Al3+ > 1-Y3+ > 1-Lu3+ > 1-Zn2+ > 1-Mg2+ > 1-Ca2+, follows the Lewis acidity of Mn+ bound to the Mn-O moiety; that is, the stronger the Lewis acidity of Mn+, the higher the reactivity of 1-Mn+ becomes. In sharp contrast, the reactivity of 1-Mn+ in the HAT reaction was reversed, giving the reactivity order 1-Ca2+ > 1-Mg2+ > 1-Zn2+ > 1-Lu3+> 1-Y3+> 1-Al3+ ≈ 1-Sc3+ that is, the higher is Lewis acidity of Mn+, the lower the reactivity of 1-Mn+ in the HAT reaction. The latter result implies that the Lewis acidity of Mn+ bound to the Mn-O moiety can modulate the basicity of the metal-oxo moiety, thus influencing the HAT reactivity of 1-Mn+ cytochrome P450 utilizes the axial thiolate ligand to increase the basicity of the iron-oxo moiety, which enhances the reactivity of compound I in C-H bond activation reactions. © 2018 American Chemical Society
Role of Elective Nodal Irradiation in Patients With ypN0 After Neoadjuvant Chemotherapy Followed by Breast-Conserving Surgery (KROG 16-16)
No full textBackground: Given the lack of established indications for elective nodal irradiation (ENI) in ypN0 patients after neoadjuvant chemotherapy (NAC) and breast-conserving surgery (BCS), we set out to investigate the role of ENI in ypN0 patients according to subtype and pathologic complete remission (pCR) status. Patients and Methods: We analyzed 261 patients who received NAC followed by BCS and adjuvant radiotherapy in 13 institutions of the Korean Radiation Oncology Group from 2005 to 2011. The tumors were classified into one of 3 subtypes: luminal (estrogen receptor positive or progesterone receptor positive and HER2 negative), HER2 (HER2 positive), or triple negative (estrogen receptor, progesterone receptor, and HER2 negative). We compared locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) according to ENI in different subgroups generated by the subtype and pCR statuses. Results: In all patients, the 5-year LRC, DFS, and OS rates were 96.0%, 91.0%, and 96.8%, respectively. In all patients, axillary lymph node dissection was found to be the only favorable factor for LRC (P =.023) and DFS (P =.001). Age ≥ 50 years (P =.027), negative resection margin (P =.002), and axillary lymph node dissection (P =.002) were all favorable factors for OS. ENI did not affect LRC, DFS, or OS. Subgroup analysis by tumor subtype and pCR showed that ENI was not associated with greater LRC or DFS in any subgroups. Conclusion: In ypN0 patients after NAC and BCS, ENI did not improve LRC or survival, regardless of subtype or primary tumor response. This result should be verified through larger prospective trials. © 2018 Elsevier Inc.This multi-institutional study aimed to investigate the role of elective nodal irradiation (ENI) in ypN0 patients following neoadjuvant chemotherapy and breast-conserving surgery according to subtype and primary tumor response. We analyzed 261 patients and found that ENI does not improve survival regardless of subtype or primary tumor response. Whole-breast irradiation might be sufficient in ypN0 patients. © 2018 Elsevier Inc
Alterations in structural rich-club connectivity of the precuneus are associated with depressive symptoms among individuals with subjective memory complaints
No full textThe association between subjective memory complaints (SMCs) and depressive symptoms has been widely reported and both have been regarded as risk factors for dementia, such as Alzheimer’s disease (AD). Although SMCs arise as early as in middle age, the exact neural correlates of comorbid depressive symptoms among individuals who are middle-aged and with SMCs have not yet been well investigated. Because rich-club organization of the brain plays a key role in the pathophysiology of various neuropsychiatric disorders, the investigation of rich club organization may provide insight regarding the neurobiological mechanisms of depressive symptoms in SMCs. In the current study, we compared the rich-club organization in the structural brain connectivity between individuals who have SMCs along with depressive symptoms (SMCD) and individuals with SMCs but without depressive symptoms (SMCO). A total of 53 individuals with SMCD and 91 individuals with SMCO participated in the study. For all participants, high-resolution, T1-weighted images and diffusion tensor images were obtained, and the network analysis was performed. Individuals with SMCD had lower connectivity strength between the precuneus and other rich-club nodes than those with SMCO, which was significant after adjusting for potential confounders. Our findings suggest that disruptions of rich-club connectivity strength of the precuenus are associated with depressive symptoms in middle-aged individuals with SMCs. Given that the precuneus is one of the commonly affected regions in the early stages of AD, our findings may imply that the concomitant depressive symptoms in middle-aged individuals with SMCs could reflect structural alterations related to AD. © 2018, Psychonomic Society, Inc
C1q nephropathy in adults is a form of focal segmental glomerulosclerosis in terms of clinical characteristics
No full textAlthough C1q nephropathy (C1qN) was introduced three decades ago, the clinical significance and renal outcomes of C1qN remain unclear. This study aimed to evaluate the clinical characteristics of C1qN, including renal outcomes, by performing a matched comparison within a multicenter cohort. We enrolled 6,413 adult patients who underwent kidney biopsy between January 2000 and January 2018 at three tertiary hospitals in Korea. We compared the clinical characteristics of 23 patients with C1qN with those of patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) who were matched by age, sex, diabetic status, and a period of biopsy. Histological and clinical parameters in patients with C1qN were also evaluated according to the different pathological phenotypes. For a mean follow-up period of 92 months, 4 patients with C1qN (17.4%) developed end-stage renal disease (ESRD). None of the matched patients with MCD had ESRD, but 7 (30.4%) of patients with FSGS progressed to ESRD, which was not different from that of C1qN patients (p = 0.491). Laboratory and pathological findings, except segmental glomerulosclerosis, were not notably different between FSGS and C1qN. The presence of segmental glomerulosclerosis, mesangial hypercellularity, and podocyte effacement did not affect both the short-and long-term renal outcomes in patients with C1qN. Our study showed that the renal outcomes of C1qN are comparable with those of FSGS, and not with MCD. Specific pathological findings, including segmental glomerulosclerosis in C1qN, were not associated with renal outcomes, which may suggest homogeneity in the clinical features of C1qN
The relationships of blood lead level, body mass index, and osteoarthritis in postmenopausal women
No full textObjectives: It is unclear whether blood lead level (BLL) is associated with osteoarthritis (OA). The objectives of this study were to address the relationship between BLL and OA and to assess whether degree of obesity, evaluated as body mass index (BMI), mediates BLL-related OA. Study design: This study was performed using data obtained from 884 postmenopausal women (≥55 years old) in the Korea National Health and Nutrition Examination Survey 2010-2012. OA in back, hip, and knee was assessed by radiographic examination (rOA) and radiographic examination and symptoms (sxOA). Multivariable logistic regression analyses were performed to investigate the BLL–OA relationship. Mediation analyses were performed to address the contribution of BMI to BLL-related OA. Results: Odds ratio (OR) for knee rOA with the highest tertile of BLL was 1.56 [95% confidence interval (CI) = 1.08–2.25] compared with the lowest tertile; there were significant linear trends across tertiles. With adjustments for confounders without BMI, continuous BLL was significantly associated with rOA (OR = 1.89, 95% CI = 1.27–2.80) and sxOA (OR = 1.69, 95% CI = 1.03–2.80) in the knee. After further adjusting for BMI, however, these significances were attenuated or disappeared. BMI was significantly associated with BLL, rOA of knee, and sxOA of knee and back. BMI significantly mediated the BLL–rOA association of the knee (21.1%) and back (46.5%) and the BLL–sxOA association of the knee (22.0%). The population-attributable fraction of rOA caused by BLL greater than the median (2.216 μg/dL) was 8.7% (95% CI = 1.1%–16.2%, P value = 0.024). Conclusions: BLL was significantly associated with knee OA in Korean postmenopausal women. BMI considerably mediated the effects of BLL on knee OA. © 2019 Elsevier B.V
Interarm Blood Pressure Difference has Various Associations with the Presence and Burden of Cerebral Small-Vessel Diseases in Noncardioembolic Stroke Patients
No full textBackground and Purpose An interarm blood pressure difference (IABD) is independently related to the occurrence of cardiovascular disease and mortality. Cerebral small-vessel diseases (SVDs) are important risk factors for stroke, cognitive dysfunction, and mortality. We aimed to determine whether IABD is related to cerebral SVDs. Methods This study included 1,205 consecutive noncardioembolic ischemic stroke patients as confirmed by brain MRI and simultaneously measured the bilateral brachial blood pressures. We investigated cerebral SVDs based on high-grade white-matter hyperintensities (HWHs), presence of cerebral microbleeds (CMBs), high-grade perivascular spaces (HPVSs), and asymptomatic lacunar infarctions (ALIs) on brain MRI. Results In multivariate logistic regression, an interarm systolic blood pressure difference (IASBD) >= 10 mm Hg was independently related to the existence of HWHs [odds ratio (OR)= 1.94, 95% CI=1.32-2.84, p=0.011] and had a tendency to be associated with the presence of HPVSs (OR=1.45, 95% CI=0.49-2.23, p=0.089) and ALIs (OR=1.42, 95% CI=0.96-2.11, p=0.052), but not with the presence of CMBs (OR=1.09, 95% CI=0.73-1.61, p=0.634). In multi-variate linear regression adjusted for age, sex, and variables with p<0.1 in the univariate analysis, IASBD >= 10 mm Hg and interarm diastolic blood pressure difference >= 10 mm Hg were significantly correlated with an increased total burden of SVDs (beta=0.080 and p=0.006, and beta=0.065 and p=0.023, respectively). Conclusions This study found that IABD >= 10 mm Hg was associated with the presence and increased burden of cerebral SVDs in noncardioembolic stroke patients. This suggests that IABD >= 10 mm Hg could be a useful indicator of the presence and burden of cerebral SVDs in stroke patients
Comparative Study on Hydrogen Evolution Reaction Activity of Electrospun Nanofibers with Diverse Metallic Ir and IrO2 Composition Ratios
No full textHydrogen evolution reaction (HER) is of importance in energy conversion processes. This paper reports the facile synthesis of iridium/iridium oxide nanofibers (Ir/IrO(2)NFs) with diverse Ir and IrO2 relative composition ratios and their electrocatalytic HER activities. Highly porous Ir/IrO(2)NFs are simply synthesized via electrospinning and the following calcination at various temperatures (300-900 degrees C). Different calcination temperature alters the actual composition of Ir/IrO(2)NFs: The higher the temperature, the greater IrO2 content exists. The HER activity of Ir/IrO(2)NFs is examined in 1 M H2SO4. Ir/IrO2NF calcined at 300 degrees C exhibits the best HER activity in terms of the onset potential, overpotential generating 50 mA cm(-2), turnover frequency, Tafel slope along with the decent stability for 5 h; the HER performance of this material even exceeds that of platinum, a benchmark HER catalyst. As the IrO2 content in Ir/IrO(2)NFs increases with a higher calcination temperature, the HER activity decreases. Ir/IrO2NF calcined at 900 degrees C consists of only IrO2 and presents the worst activity. DFT calculations show that hydrogen atom adsorption on metallic Ir (not IrO2) resembles that on Pt: similar adsorption energy and adsorbate-substrate distance. Both the experimental and theoretical results clearly demonstrate that metallic Ir rather than IrO2 is a good HER catalytic platform
Effect of semiconductor polymer backbone structures and side-chain parameters on the facile separation of semiconducting single-walled carbon nanotubes from as-synthesized mixtures
No full textSemiconducting single-walled carbon nanotubes (SWNTs) show promise as core materials for next generation solar cells and nanoelectronic devices. However, most commercial SWNT production methods generate mixtures of metallic SWNTs (m-SWNTs) and semiconducting SWNT (sc-SWNTs). Therefore, sc-SWNTs must be separated from their original mixtures before use. In this study, we investigated a polymer-based, noncovalent sc-SWNT separation approach, which is simple to perform and does not disrupt the electrical properties of the SWNTs, thus improving the performance of the corresponding sc-SWNT-based applications. By systematically investigating the effect that different structural features of the semiconductor polymer have on the separation of sc-SWNTs, we discovered that the length and configuration of the alkyl side chains and the rigidity of the backbone structure exert significant effects on the efficiency of sc-SWNT separation. We also found that electron transfer between the semiconductor polymers and sc-SWNTs is strongly affected by their energy-level alignment, which can be tailored by controlling the donor-acceptor configuration in the polymer backbone structures. Among the polymers investigated, the highly planar P8T2Z-C12 semiconductor polymer showed the best sc-SWNT separation efficiency and unprecedentedly strong electronic interaction with the sc-SWNTs, which is important for improving their performance in applications. (C) 2017 Elsevier B.V. All rights reserved
First Measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary-Black-hole Merger GW170814
No full textWe present a multi-messenger measurement of the Hubble constant H-0 using the binary-black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in H-0 = 75(-32)(+40) km s(-1) Mpc(-1) , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s(-1) Mpc(-1) , and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s(-1) Mpc(-1) , we find H-0 = 78(-24)(+96) km s(-1) Mpc(-1) (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H-0