Antidepressant-like Effects of Chinese Quince (Chaenomeles sinensis) Fruit Based on In Vivo and Molecular Docking Studies.

In this study, we examined the potential antidepressant-like effects of Chinese quince fruit extract (Chaenomeles sinensis fruit extract, CSFE) in an in vivo model induced by repeated injection of corticosterone (CORT)-induced depression. HPLC analysis determined that chlorogenic acid (CGA), neo-chlorogenic acid (neo-CGA), and rutin (RT) compounds were major constituents in CSFE. Male ICR mice (5 weeks old) were orally administered various doses (30, 100, and 300 mg/kg) of CSFE and selegiline (10 mg/kg), a monoamine oxidase B (MAO-B) inhibitor, as a positive control following daily intraperitoneal injections of CORT (40 mg/kg) for 21 days. In our results, mice treated with CSFE exhibited significant improvements in depressive-like behaviors induced by CORT. This was evidenced by reduced immobility times in the tail suspension test and forced swim test, as well as increased step-through latency times in the passive avoidance test. Indeed, mice treated with CSFE also exhibited a significant decrease in anxiety-like behaviors as measured by the elevated plus maze test. Moreover, molecular docking analysis indicated that CGA and neo-CGA from CSFE had stronger binding to the active site of MAO-B. Our results indicate that CSFE has potential antidepressant effects in a mouse model of repeated injections of CORT-induced depression.

The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments.

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children's height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.

Dried Loquat Fruit Extract Containing Chlorogenic Acid Prevents Depressive-like Behaviors Induced by Repeated Corticosteroid Injections in Mice.

Eriobotrya japonica (loquat tree) has been used in traditional medicine to treat respiratory ailments, inflammation, and skin diseases; however, its potential antidepressant-like effects have not been extensively investigated. In this study, we evaluated the antidepressant-like effects of E. japonica fruit extract (EJFE) in a mouse model of corticosterone (CORT)-induced depression. An HPLC analysis revealed that chlorogenic acid (CGA) is the major compound in EJFE. Male ICR mice (5weeks-old) were injected with CORT (40 mg/kg, intraperitoneally) once daily for 21 days to induce depressive-like behaviors. Various behavioral tests, including the open field test, rotarod test, elevated plus maze (EPM), passive avoidance test (PAT), tail suspension test (TST), and forced swim test (FST), were conducted 1 h after the oral administration of EJFE at different doses (30, 100, and 300 mg/kg) and CGA (30 mg/kg). High-dose EJFE and CGA significantly alleviated CORT-induced depressive-like behaviors, as indicated by the reduced immobility times in the TST and FST. A decrease in the step-through latency time in the PAT, without an effect on locomotor activity, suggested an improvement in cognitive function. Moreover, EJFE- and CGA-treated mice exhibited significantly reduced anxiety-like behaviors in the EPM. Our results imply the promising potential of EJFE containing CGA as a therapeutic candidate for depression.

In situ x-ray-induced acoustic computed tomography with a contrast agent: a proof of concept.

X-ray-induced acoustic computed tomography (XACT) has shown great potential as a hybrid imaging modality for real-time non-invasive x-ray dosimetry and low-dose three-dimensional (3D) imaging. While promising, one drawback of the XACT system is the underlying low signal-to-noise ratio (SNR), limiting its in vivo clinical use. In this Letter, we propose the first use of a conventional x-ray computed tomography contrast agent, Gastrografin, for improving the SNR of in situ XACT imaging. We obtained 3D volumetric XACT images of a mouse's stomach with orally injected Gastrografin establishing the proposal's feasibility. Thus, we believe, in the future, our proposed technique will allow in vivo imaging and expand or complement conventional x-ray modalities, such as radiotherapy and accelerators.

Pedicularis resupinata Extract Prevents Depressive-like Behavior in Repeated Corticosterone-Induced Depression in Mice: A Preliminary Study.

Excessive corticosterone (CORT), resulting from a dysregulated hypothalamic-pituitary-adrenal (HPA) axis, is associated with cognitive impairment and behavioral changes, including depression. In Korean oriental medicine, Pedicularis resupinata is used for the treatment of inflammatory diseases such as rheumatoid arthritis. However, the antidepressant properties of P. resupinata have not been well characterized. Here, the antidepressant-like effects of P. resupinata extract (PRE) were evaluated in terms of CORT-induced depression using in vivo models. HPLC confirmed that acteoside, a phenylethanoid glycoside, was the main compound from PRE. Male ICR mice (8 weeks old) were injected with CORT (40 mg/kg, i.p.) and orally administered PRE daily (30, 100, and 300 mg/kg) for 21 consecutive days. Depressive-like behaviors were evaluated using the open-field test, sucrose preference test, passive avoidance test, tail suspension test, and forced swim test. Treatment with a high dose of PRE significantly alleviated CORT-induced, depressive-like behaviors in mice. Additionally, repeated CORT injection markedly reduced brain-derived neurotrophic factor levels, whereas total glucocorticoid receptor (GR) and GR phosphorylation at serine 211 were significantly increased in the mice hippocampus but improved by PRE treatment. Thus, our findings suggest that PRE has potential antidepressant-like effects in CORT-induced, depressive-like behavior in mice.

d-dimer Level as a Predictor of Recurrent Stroke in Patients With Embolic Stroke of Undetermined Source.

Background and Purpose: This study aimed to investigate the value of d-dimer levels in predicting recurrent stroke in patients with embolic stroke of undetermined source. We also evaluated the underlying causes of recurrent stroke according to d-dimer levels. Methods: A total of 1431 patients with undetermined source were enrolled in this study and divided into quartiles according to their baseline plasma d-dimer levels. The primary outcome measure was the occurrence of recurrent stroke (ischemic or hemorrhagic) in the year following the stroke event. Results: The risk of recurrent stroke increased significantly with the increasing d-dimer quartile (log-rank P=0.001). Patients in the higher d-dimer quartiles had a higher probability of recurrent embolic stroke because of covert atrial fibrillation, hidden malignancy, or undetermined sources. Most recurrent strokes in Q3 and Q4 were embolic but not in Q1 or Q2. Multivariate analysis revealed that patients in Q3 and Q4 had a significantly increased risk of recurrent stroke compared with those in Q1 (hazard ratio, 3.12 [95% CI, 1.07−9.07], P=0.036; hazard ratio, 7.29 [95% CI, 2.59−20.52], P<0.001, respectively; Ptrend<0.001). Binary analyses showed a significant association between a high d-dimer level above normal range and the risk of recurrent stroke (hazard ratio, 2.48 [95% CI, 1.31−4.70], P=0.005). In subgroup analyses, a high d-dimer level was associated with a significantly higher risk of recurrent stroke in men than in women (P=0.039). Conclusions: Our findings suggest that d-dimer levels can be a useful risk assessment biomarker for predicting recurrent stroke, especially embolic ischemic stroke, in patients with undetermined source.

Recent Advances in Imaging Sensors and Applications.

Recent advances in sensor technology have allowed us to develop many interesting applications and enhance the quality of human life [...].

Pilot Study: Quantitative Photoacoustic Evaluation of Peripheral Vascular Dynamics Induced by Carfilzomib In Vivo.

Carfilzomib is mainly used to treat multiple myeloma. Several side effects have been reported in patients treated with carfilzomib, especially those associated with cardiovascular events, such as hypertension, congestive heart failure, and coronary artery disease. However, the side effects, especially the manifestation of cardiovascular events through capillaries, have not been fully investigated. Here, we performed a pilot experiment to monitor peripheral vascular dynamics in a mouse ear under the effects of carfilzomib using a quantitative photoacoustic vascular evaluation method. Before and after injecting the carfilzomib, bortezomib, and PBS solutions, we acquired high-resolution three-dimensional PAM data of the peripheral vasculature of the mouse ear during each experiment for 10 h. Then, the PAM maximum amplitude projection (MAP) images and five quantitative vascular parameters, i.e., photoacoustic (PA) signal, diameter, density, length fraction, and fractal dimension, were estimated. Quantitative results showed that carfilzomib induces a strong effect on the peripheral vascular system through a significant increase in all vascular parameters up to 50%, especially during the first 30 min after injection. Meanwhile, bortezomib and PBS do not have much impact on the peripheral vascular system. This pilot study verified PAM as a comprehensive method to investigate peripheral vasculature, along with the effects of carfilzomib. Therefore, we expect that PAM may be useful to predict cardiovascular events caused by carfilzomib.

In Vivo Quantitative Vasculature Segmentation and Assessment for Photodynamic Therapy Process Monitoring Using Photoacoustic Microscopy.

Vascular damage is one of the therapeutic mechanisms of photodynamic therapy (PDT). In particular, short-term PDT treatments can effectively destroy malignant lesions while minimizing damage to nonmalignant tissue. In this study, we investigate the feasibility of label-free quantitative photoacoustic microscopy (PAM) for monitoring the vasculature changes under the effect of PDT in mouse ear melanoma tumors. In particular, quantitative vasculature evaluation was conducted based on Hessian filter segmentation. Three-dimensional morphological PAM and depth-resolved images before and after PDT treatment were acquired. In addition, five quantitative vasculature parameters, including the PA signal, vessel diameter, vessel density, perfused vessel density, and vessel complexity, were analyzed to evaluate the influence of PDT on four different areas: Two melanoma tumors, and control and normal vessel areas. The quantitative and qualitative results successfully demonstrated the potential of the proposed PAM-based quantitative approach to evaluate the effectiveness of the PDT method.

Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats.

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.

Microbleeds and Outcome in Patients With Acute Ischemic Stroke and Atrial Fibrillation Taking Anticoagulants.

BACKGROUND AND PURPOSE: We investigated the impact of the presence, burden, and location of cerebral microbleeds (CMBs) on the risk of major adverse cerebrovascular and cardiovascular events (MACCE) in patients with acute ischemic stroke and atrial fibrillation treated with oral anticoagulants (OACs). We also examined whether the clinical effect of CMBs differs according to the type of OACs. METHODS: A total of 1742 patients with acute ischemic stroke and atrial fibrillation treated with OACs were enrolled in this cohort study. The primary composite outcome was the occurrence of MACCE (a composite of stroke, acute myocardial infarction, or vascular death) over a 2-year period according to CMB status. RESULTS: CMB presence was significantly associated with the risk of future MACCE (hazard ratio, 1.89 [95% CI, 1.23-2.88]; P=0.003) after adjustment for confounders in patients with acute ischemic stroke and atrial fibrillation taking OACs. Patients with exactly 1 CMB had a similar rate of MACCE compared with those without CMBs (P=0.461). However, patients with multiple CMBs (≥2), particularly high burden CMBs (≥5), had a significantly higher proportion of MACCE. Both CMB-positive groups with lobar and deep CMB had more frequent MACCE than the CMB-negative group, and the rate of MACCE was not different according to CMB location. In patients treated with warfarin, CMB was significantly associated with a risk of MACCE (P=0.002), but not in patients treated with direct OACs (P=0.517). CONCLUSIONS: The study results indicate that the risk of future MACCE increased with increasing CMB burden in patients with AIS and atrial fibrillation taking OACs, while the anatomic location of CMBs did not influence the risk of future MACCE. This risk seemed to be more apparent in patients taking warfarin.

Dicaffeoylquinic acids alleviate memory loss via reduction of oxidative stress in stress-hormone-induced depressive mice.

Chronic stress can lead to depression due to elevated levels of stress hormones such as glucocorticoid. This is accompanied by an increase in reactive oxygen species (ROS) levels in the brain, which can cause dendritic spine loss and atrophy in neurons, followed by memory loss. Dicaffeoylquinic acids (diCQAs) are naturally occurring polyphenolic antioxidant compounds in Arctium lappa extracts (AL). The effects of natural derivatives of cafferoylqunic acid on stress hormone-induced depressive behavior and their underlying mechanisms are uncertain. In the current study, we showed that diCQAs reduced depressive behaviors including memory loss in corticosterone (CORT) treated mice. The mechanism of anti-depressants of diCQAs is likely through reduction of ROS production by inhibiting the activity of monoamine oxidase (MAO) type A and B in neurons and astrocytes. Among diCQAs, 3,4- and 3,5-diCQA significantly inhibited the activity of MAO enzymes followed by the reduction of ROS in neurons and astrocytes and also protected neuronal atrophy and synaptic transmission against stress hormone. These results suggest that 3,4- and 3,5-diCQAs effectively reduced depressive symptoms and inhibited ROS production to alleviate memory loss in stress hormone-induced depressive mice and hence, which provide some potential natural antidepressants.

Synthesis and inhibitory effect of cis-guggulsterone on lipopolysaccharide-induced production of nitric oxide in macrophages.

Guggulsterone is a bioactive plant sterol naturally found in migratory plants. It exists in various forms, and its active compounds include the isomers cis-guggulsterone (E-GS) and trans-guggulsterone (Z-GS). In this study, the anti-inflammatory effects of these two isomeric pregnadienedione steroids were investigated against lipopolysaccharide-induced inflammatory reaction in RAW264.7 mouse macrophages. Our results showed that both guggulsterones inhibited the production of NO in macrophages treated with lipopolysaccharide, with IC50 values ranging from 3.0 to 6.7 µM. E-GS exerted higher efficacy than Z-GS, and its anti-inflammatory effects was mediated through inhibition of iNOS and COX-2 expression.

Herpes zoster does not increase the risk of sudden sensory neural hearing loss: a longitudinal follow-up study using a national sample cohort.

Objective: This study aimed to investigate the risk of sudden sensorineural hearing loss (SSNHL) in Herpes zoster patients from a representative population cohort.Design: A longitudinal follow-up studyStudy sample: Data were obtained from the Korean National Health Insurance Service-National Sample Cohort for the period from 2002 to 2013. We matched 61,702 subjects in the Herpes zoster group with subjects in a control group (246,808 subjects with no history of Herpes zoster) based on demographic factors (age, sex, income, and region of residence) and medical history (diabetes, dyslipidemia, and hypertension). The crude (simple) and adjusted hazard ratios (HRs) for Herpes zoster with SSNHL were analysed using the Cox-proportional hazard model.Results: Only 0.5% (338/61,364) of the Herpes zoster group and 0.7% (1664/245,144) of the control group showed SSNHL. The Herpes zoster group did not exhibit a higher rate of SSNHL (adjusted HR = 0.81, 95% CI = 0.72-0.91, p < 0.001) than the control group. In subgroup analyses, no age subgroups showed a significant risk of SSNHL in the Herpes zoster group.Conclusions: After adjusting for confounding factors, the risk of SSNHL did not increase in the Herpes zoster group compared with the control group.

Modified Fixed Wall Oedometer When Considering Stress Dependence of Elastic Wave Velocities.

A modified oedometer cell for measuring the applied stresses and elastic waves at the top and bottom of the specimen is developed to evaluate the effect of the side friction on the stress dependence of the elastic wave velocities. In the modified cell, two load cells are installed at the top and bottom plates, respectively. To generate and detect the compressional and shear waves, a pair of piezo disk elements and a pair of bender elements are mounted at both the top and bottom plates. Experimental results show that the stresses measured at the bottom are smaller than those measured at the top during the loading and vice versa during unloading, regardless of the densities and heights of the specimens. Under nearly saturated conditions, the compressional wave velocities remain almost constant for the entire stress state. With plotting stresses measured at top, the shear wave velocities during unloading are greater than those during loading, whereas with plotting stresses measured at bottom, the shear wave velocities during unloading are smaller than those during loading owing to the side friction. The vertical effective stress may be simply determined from the average values of the stresses measured at the top and bottom of the specimens.

Feasibility Study of Precise Balloon Catheter Tracking and Visualization with Fast Photoacoustic Microscopy.

Correct guiding of the catheter is a critical issue in almost all balloon catheter applications, including arterial stenosis expansion, coronary arterial diseases, and gastrointestinal tracking. To achieve safe and precise guiding of the balloon catheter, a novel imaging method with high-resolution, sufficient depth of penetration, and real-time display is required. Here, we present a new balloon catheter guiding method using fast photoacoustic microscopy (PAM) technique for precise balloon catheter tracking and visualization as a feasibility study. We implemented ex vivo and in vivo experiments with three different medium conditions of balloon catheter: no air, air, and water. Acquired cross-sectional, maximum amplitude projection (MAP), and volumetric 3D PAM images demonstrated its capability as a new imaging guiding tool for balloon catheter tracking and visualization.

Distribution and diastereoisomeric profiles of hexabromocyclododecanes in air, water, soil, and sediment samples in South Korea: Application of an optimized analytical method.

In this study, the levels and distribution patterns of HBCD diastereoisomers in air, water, soil, and sediment samples in South Korea were investigated after optimizing the UPLC-MS/MS analytical process. Extraction and cleanup efficiencies were tested using several different extraction solvents and adsorbents. Dichloromethane was selected as the base extraction solvent, and multi-layer silica gel (MSG) and MSG-alumina columns were selected for the removal of HBCDs from complex environmental matrices. The concentration of Æ©3 HBCDs was 22-133 pg/m3, 10-128 ng/g, 0.2-151 ng/L, and 0.5-552 ng/g dw for air, soil, water, and sediment samples, respectively. Relatively higher concentrations of Æ©3 HBCDs were observed at stations adjacent to industrial facilities (e.g., rubber and plastic, textile, chemical, fabricated metal, and wholesale trade factories) associated with the use of commercial HBCDs. The proportion of γ-HBCD in the soil (48.3-86.2%) and sediment (54.2-78.1%, except for one station) samples was similar to that found in technical and commercial HBCDs. In contrast, α-HBCD (52.3-71.2%) was dominant in all air samples, while the water samples displayed no clear trend in their diastereoisomer profiles. As the first nationwide report on HBCD diastereoisomers in the environment, this study demonstrates that most environmental compartments in South Korea are moderately contaminated with HBCDs.

Standardized Citrus unshiu peel extract ameliorates dexamethasone-induced neurotoxicity and depressive-like behaviors in mice.

Dried Citrus unshiu peel, also known as Chinpi, have been commonly used as a traditional medicine to improve for allergy, inflammation and hepatopathy. Many previously studies have reported that citrus flavonoids show neuroprotective activities. However, the antidepressant-related effects of C. unshiu peels have not been well characterized. Here, the antidepressant-like effects of standardized C. unshiu peel extract (SCP) were evaluated in in vivo and in vitro depression models induced by dexamethasone (DEX), a synthetic glucocorticoid. Male ICR mice (9-week-old) were injected the DEX (40 mg/kg) and were orally given SCP daily (30, 100, and 300 mg/kg) for 14 consecutive days. The depressive-like behaviors were determined by use of open filed test (OFT), sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST). We show that treatment with SCP significantly alleviated DEX-induced depressive-like behaviors and reduced neurotoxicity in a concentration dependent manner in SH-SY5Y cells. Additionally, repeated DEX injection markedly decreased brain derived neurotrophic factor (BDNF) level, tropomyosin receptor kinase B (TrkB), and cyclic AMP-response element-binding protein (CREB), while SCP treatment improved these levels in the cerebral cortex and hippocampus regions. Our findings suggest that SCP exhibits significant antidepressant-like effects in the DEX-induced depressive animal model, and this activity may be mediated by preventing corticosterone-induced neurotoxicity.

Antidepressant-Like Effects of Lindera obtusiloba Extracts on the Immobility Behavior of Rats in the Forced Swim Test.

Lindera obtusiloba extracts are commonly used as an alternative medicine due to its numerous health benefits in Korea. However, the antidepressant-like effects of L. obtusiloba extracts have not been fully elucidated. In this study, we aimed to determine whether L. obtusiloba extracts exhibited antidepressant-like activity in rats subjected to forced swim test (FST)-induced depression. Acute treatment of rats with L. obtusiloba extracts (200 mg/kg, p.o.) significantly reduced immobility time and increased swimming time without any significant change in climbing. Rats treated with L. obtusiloba extracts also exhibited a decrease in the limbic hypothalamic-pituitary-adrenal (HPA) axis response to the FST, as indicated by attenuation of the corticosterone response and decreased c-Fos immunoreactivity in the hippocampus CA3 region. In addition, L. obtusiloba extracts, at concentrations that were not affected by cell viability, significantly decreased luciferase activity in response to cortisol in a concentration-dependent manner by the glucocorticoid binding assay in HeLa cells. Our findings suggested that the antidepressant-like effects of L. obtusiloba extracts were likely mediated via the glucocorticoid receptor (GR). Further studies are needed to evaluate the potential of L. obtusiloba extracts as an alternative therapeutic approach for the treatment of depression.

Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice.