Neuroprotective Effects of a Traditional Multi-Herbal Medicine Kyung-Ok-Ko in an Animal Model of Parkinson's Disease: Inhibition of MAPKs and NF-κB Pathways and Activation of Keap1-Nrf2 Pathway

Kyung-Ok-Ko (KOK), a traditional multi-herbal medicine, has been widely used in Oriental medicine as a restorative that can enforce vitality of whole organs and as a medicine that can treat age-related symptoms including lack of vigor and weakened immunity. However, the beneficial effect of KOK on neurological diseases such as Parkinson's diseases (PD) is largely unknown. Thus, the objective of this study was to examine the protective effect of KOK on neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-treatment with KOK at 1 or 2 g/kg/day (p.o.) showed significant mitigating effects on neurological dysfunction (motor and welfare) based on pole, rotarod, and nest building tests. It also showed effects on survival rate. These positive effects of KOK were related to inhibition of loss of tyrosine hydroxylase–positive neurons, reduction of MitoSOX activity, increased apoptotic cells, microglia activation, and upregulation of inflammatory factors [interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide], and reduced blood-brain barrier (BBB) disruption in the substantia nigra pars compacta (SNpc) and/or striatum after MPTP intoxication. Interestingly, these effects of KOK against MPTP neurotoxicity were associated with inhibition of phosphorylation of mitogen-activated protein kinases and nuclear factor-kappa B signaling pathways along with up-regulation of nuclear factor erythroid 2-related factor 2 pathways in SNpc and/or striatum. Collectively, our findings suggest that KOK might be able to mitigate neurotoxicity in MPTP-induced mouse model of PD via multi-effects, including anti-neuronal and anti-BBB disruption activities through its anti-inflammatory and anti-oxidative activities. Therefore, KOK might have potential for preventing and/or treating PD

Comparing Results of Five Glomerular Filtration Rate-Estimating Equations in the Korean General Population. MDRD Study, Revised Lund-Malmö, and Three CKD-EPI Equations

Estimated glomerular filtration rate (eGFR) is a widely used index of kidney function. Recently, new formulas such as the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations or the Lund-Malmö equation were introduced for assessing eGFR. We compared them with the Modification of Diet in Renal Disease (MDRD) Study equation in the Korean adult population. METHODS: The study population comprised 1,482 individuals (median age 51 [42-59] yr, 48.9% males) who received annual physical check-ups during the year 2014. Serum creatinine (Cr) and cystatin C (CysC) were measured. We conducted a retrospective analysis using five GFR estimating equations (MDRD Study, revised Lund-Malmö, and Cr and/or CysC-based CKD-EPI equations). Reduced GFR was defined as eGFR <60 mL/min/1.73 m². RESULTS: For the GFR category distribution, large discrepancies were observed depending on the equation used; category G1 (≥90 mL/min/1.73 m²) ranged from 7.4-81.8%. Compared with the MDRD Study equation, the other four equations overestimated GFR, and CysC-based equations showed a greater difference (-31.3 for CKD-EPI(CysC) and -20.5 for CKD-EPI(Cr-CysC)). CysC-based equations decreased the prevalence of reduced GFR by one third (9.4% in the MDRD Study and 2.4% in CKD-EPI(CysC)). CONCLUSIONS: Our data shows that there are remarkable differences in eGFR assessment in the Korean population depending on the equation used, especially in normal or mildly decreased categories. Further prospective studies are necessary in various clinical settings

A supercritical oil extract of Schisandra chinensis seeds ameliorates Huntington’s disease-like symptoms and neuropathology: the potential role of anti-oxidant and anti-inflammatory effects

BackgroundHuntington disease (HD), a neurodegenerative autosomal dominant disorder, is characterized by involuntary choreatic movements with cognitive and behavioral disturbances. Up to now, no therapeutic strategies are available to completely ameliorate the progression of HD. Schisandra chinensis has various pharmacologic effects such as antioxidant and anti-inflammatory activities. However, the neuroprotective value of seed oil of S. chinensis (SOSC) has not been elucidated yet. The purpose of this study was to determine neuroprotective effects of SOSC by supercritical fluid extraction against 3-nitropropionic acid (3-NPA)-induced HD-like symptoms and neuropathology in an experimental mouse model.MethodsSOSC (75, 150, and 300 mg/kg/day) was orally pre-administration once daily at 1 hour before 3-NPA intoxication.ResultsSOSC ameliorated movement dysfunction and lethality following 3-NPA intoxication in connection with reduction of lesion area, neurodegeneration/apoptosis, microglial migration/activation, and mRNA expression of pro-inflammatory cytokines/enzymes in the striatum. SOSC inhibited the activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPKs) pathways but stimulated nuclear factor erythroid 2-related factor 2 (Nrf2) in the striatum after 3-NPA intoxication. Schizandrin, a main component of SOSC, reduced protein expression levels of Iba-1 and p-NF-κB in 3-NPA-induced BV2 cells (murine microglia cell line). BV2 cell’s conditioned medium inhibited cleaved caspase-3 in 3-NPA-induced SH-SY5Y cells (a neuroblastoma cell line).ConclusionSOSC might ameliorate movement dysfunction by inhibiting neuropathology through its anti-inflammatory and antioxidant activities in the striata of 3-NPA-intoxicated mice. These findings suggest that SOSC could serve as a promising therapeutic candidate for HD-like symptoms, providing a foundation for future treatment strategies targeting neuroinflammation and oxidative stress

Minocycline markedly reduces acute visceral nociception via inhibiting neuronal ERK phosphorylation

<p>Abstract</p> <p>Background</p> <p>Minocycline prevents the development of neuropathic and inflammatory pain by inhibiting microglial activation and postsynaptic currents. But, how minocycline obviates acute visceral pain is unclear. The present study investigated whether minocycline had an any antinociceptive effect on acetic acid-induced acute abdominal pain after intraperitoneal (i.p.) administration of saline or minocycline 1 hour before acetic acid injection (1.0%, 250 μl, i.p.).</p> <p>Results</p> <p>Minocycline (4, 10, or 40 mg/kg) significantly decreased acetic acid-induced nociception (0-60 minutes post-injection) and the enhancement in the number of c-Fos positive cells in the T5-L2 spinal cord induced by acetic acid injection. Also, the expression of spinal phosphorylated extracellular signal-regulated kinase (p-ERK) induced by acetic acid was reduced by minocycline pre-administration. Interestingly, intrathecal introduction of PD98059, an ERK upstream kinase inhibitor, markedly blocked the acetic acid-stimulated pain responses.</p> <p>Conclusions</p> <p>These results demonstrate that minocycline effectively inhibits acetic acid-induced acute abdominal nociception via the inhibition of neuronal p-ERK expression in the spinal cord, and that minocycline may have therapeutic potential in suppressing acute abdominal pain.</p

Transparent organic light-emitting diodes with different bi-directional emission colors using color-conversion capping layers

We report a study on transparent organic light-emitting diodes (OLEDs) with different bidirectional emission colors, enabled by color-conversion organic capping layers. Starting from a transparent blue OLED with an uncapped Ag top electrode exhibiting an average transmittance of 33.9%, a 4-(Dicyanomethylene)-2-methyl- 6-(4-dimethylaminostyryl)-4Hpyran (DCM)-doped tris-(8-hydroxy-quinolinato)-aluminium (Alq3) capping layer is applied to achieve color-conversion from blue to orange-red on the top side while maintaining almost unchanged device transmittance. This color-conversion capping layer does not only change the color of the top side emission, but also enhances the overall device efficiency due to the optical interaction of the capping layer with the primary blue transparent OLED. Top white emission from the transparent bi-directional OLED exhibits a correlated color temperature around 6,000K-7,000K, with excellent color stability as evidenced by an extremely small variation in color coordinate of ∆(x,y) = (0.002, 0.002) in the forward luminance range of 100-1000 cd m-2. At the same time, the blue emission color of bottom side is not influenced by the color conversion capping layer, which finally results in different emission colors of the two opposite sides of our transparent OLEDsPostprintPeer reviewe

Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus

Background: To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues. Methods: In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet. Results: Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P&lt;0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P&lt;0.05), and visual cortex (food vs. nonfood, P&lt;0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P&lt; 0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P &lt; 0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P&lt; 0.05). Conclusion: Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.Y

Reversible Proximal Renal Tubular Dysfunction after One-Time Ifosfamide Exposure

The alkylating agent ifosfamide is an anti-neoplastic used to treat various pediatric and adult malignancies. Its potential urologic toxicities include glomerulopathy, tubulopathy and hemorrhagic cystitis. This report describes a case of proximal renal tubular dysfunction and hemorrhagic cystitis in a 67-year-old male given ifosfamide for epitheloid sarcoma. He was also receiving an oral hypoglycemic agent for type 2 diabetes mellitus and had a baseline glomerular filtration rate of 51.5 mL/min/1.73 m2. Despite mesna prophylaxis, the patient experienced dysuria and gross hematuria after a single course of ifosfamide plus adriamycin. The abrupt renal impairment and serum/urine electrolyte imbalances that ensued were consistent with Fanconi's syndrome. However, normal renal function and electrolyte status were restored within 14 days, simply through supportive measures. A score of 8 by Naranjo adverse drug reaction probability scale indicated these complications were most likely treatment-related, although they developed without known predisposing factors. The currently undefined role of diabetic nephropathy in adult ifosfamide nephrotoxicity merits future investigation