Position-specific oxidation of miR-1 encodes cardiac hypertrophy.

In pathophysiology, reactive oxygen species oxidize biomolecules that contribute to disease phenotypes1. One such modification, 8-oxoguanine2 (o8G), is abundant in RNA3 but its epitranscriptional role has not been investigated for microRNAs (miRNAs). Here we specifically sequence oxidized miRNAs in a rat model of the redox-associated condition cardiac hypertrophy4. We find that position-specific o8G modifications are generated in seed regions (positions 2-8) of selective miRNAs, and function to regulate other mRNAs through o8G•A base pairing. o8G is induced predominantly at position 7 of miR-1 (7o8G-miR-1) by treatment with an adrenergic agonist. Introducing 7o8G-miR-1 or 7U-miR-1 (in which G at position 7 is substituted with U) alone is sufficient to cause cardiac hypertrophy in mice, and the mRNA targets of o8G-miR-1 function in affected phenotypes; the specific inhibition of 7o8G-miR-1 in mouse cardiomyocytes was found to attenuate cardiac hypertrophy. o8G-miR-1 is also implicated in patients with cardiomyopathy. Our findings show that the position-specific oxidation of miRNAs could serve as an epitranscriptional mechanism to coordinate pathophysiological redox-mediated gene expression.

Antioxidant Efficacy of Hwangryunhaedok-tang through Nrf2 and AMPK Signaling Pathway against Neurological Disorders In Vivo and In Vitro.

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.

The Mental Health Outcomes and Cost Estimates of Korean Medicine for Anxiety Disorder Patients.

Korean medicine (KM) is used to treat anxiety disorders, but there is limited research on its effects. This study aimed to examine the associations between improved QoL and reduced clinical symptoms and KM in patients with anxiety disorders. The medical records of patients with anxiety who were treated with KM (acupuncture, psychotherapy, Chuna therapy, aromatherapy, or herbal medicine) for at least 4 weeks were retrospectively analyzed. Clinical, QoL, and cost outcomes were measured at baseline and at weeks 4 and 12 (Anxiety: State-Trait Anxiety Inventory [STAI X-1 (state), X-2 (trait)], Beck Anxiety Inventory [BAI]; anger: State-Trait Anger Expression Inventory State [STAXI-S (state), T (trait)], Anger Expression Inventory [AXI-K-I (anger-in), AXI-K-O (anger-out), AXI-K-C (anger-control); depression: Beck Depression Inventory-II [BDI II], QoL: QoL-related instruments Euro Quality of Life 5 Dimensions utility score [EQ-5D], Euro QoL Visual Analog Scale [EQ-VAS]). The total costs for each item were calculated in terms of NHIS-covered costs and patients' out-of-pocket costs from the perspective of the healthcare system. The medical records of 67 patients were evaluated. The KM treatments were found to be associated with decreased anxiety (STAI X-1; STAI X-2; BAI, p < 0.0001), depression (BDI-II, p < 0.0001), and anger (AKI-K-I; AKI-K-O, p < 0.05) and increased QoL (EQ-5D; EQ-VAS, p < 0.0001). An average of USD 1360 was paid for the KM treatments for 4 weeks. The study findings suggested that KM may improve clinical symptoms and QoL outcomes in patients with anxiety disorders.

Effectiveness and Safety of Pattern Identification-Based Herbal Medicine for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Objective: Alzheimer's disease (AD), the most common cause of dementia, has only symptomatic treatments in conventional Western medicine (WM). Disease-modifying drugs are still under development. This study evaluated the efficacy and safety of herbal medicine (HM) based on pattern identification (PI) as a whole system practice for treating AD. Methods: Thirteen databases were searched from inception to August 31, 2021. Twenty-seven randomized controlled trials (RCTs) with 2069 patients were included in the evidence synthesis. Results: The meta-analysis showed that, compared with WM, HM prescription based on PI, either alone or in combination with WM, could significantly improve the cognitive functions of AD patients (Mini-Mental State Examination [MMSE]-HM vs. WM: mean difference [MD] = 1.96, 95% confidence intervals [CIs]: 0.28-3.64, N = 981, I2 = 96%; HM+WM vs. WM: MD = 1.33, 95% CI: 0.57-2.09, N = 695, I2 = 68%) and their ability to perform activities of daily living (ADL-HM vs. WM: standardized mean difference [SMD] = 0.71, 95% CI: 0.04-1.38, N = 639, I2 = 94%; HM+WM vs. WM: SMD = 0.60, 95% CI: 0.27-0.93, N = 669, I2 = 76%). Duration-wise, 12 weeks of HM+WM were superior to 12 weeks of WM and 24 weeks of HM were superior to 24 weeks of WM. None of the included studies found any severe safety concerns. The odds of mild-to-moderate adverse events were marginally lower in HM than in WM (odds ratio = 0.34, 95% CI: 0.11-1.02, N = 689, I2 = 55%). Conclusion: Hence, prescribing PI-based HM is a safe and effective therapeutic option for AD, either as first-line therapy or adjuvant treatment. However, most of the included studies have a high or uncertain risk of bias. Thus, well-designed RCTs with proper blinding and placebo controls are needed.

Widespread 8-oxoguanine modifications of miRNA seeds differentially regulate redox-dependent cancer development.

Oxidative stress contributes to tumourigenesis by altering gene expression. One accompanying modification, 8-oxoguanine (o8G) can change RNA-RNA interactions via o8G•A base pairing, but its regulatory roles remain elusive. Here, on the basis of o8G-induced guanine-to-thymine (o8G > T) variations featured in sequencing, we discovered widespread position-specific o8Gs in tumour microRNAs, preferentially oxidized towards 5' end seed regions (positions 2-8) with clustered sequence patterns and clinically associated with patients in lower-grade gliomas and liver hepatocellular carcinoma. We validated that o8G at position 4 of miR-124 (4o8G-miR-124) and 4o8G-let-7 suppress lower-grade gliomas, whereas 3o8G-miR-122 and 4o8G-let-7 promote malignancy of liver hepatocellular carcinoma by redirecting the target transcriptome to oncogenic regulatory pathways. Stepwise oxidation from tumour-promoting 3o8G-miR-122 to tumour-suppressing 2,3o8G-miR-122 occurs and its specific modulation in mouse liver effectively attenuates diethylnitrosamine-induced hepatocarcinogenesis. These findings provide resources and insights into epitranscriptional o8G regulation of microRNA functions, reprogrammed by redox changes, implicating its control for cancer treatment.

Study on the microstructures and the magnetic properties of precipitates in a Cu75-Fe5-Ni20 alloy.

The microstructural evolutions of precipitates formed in a Cu75-Fe5-Ni20 alloy on isothermal annealing at 873 K and 1073 K have been investigated by means of transmission electron microscopy (TEM). Nano-scale magnetic particles were formed randomly in the Cu-rich matrix after receiving a short annealing due to phase decomposition in the alloy. With increasing the isothermal annealing time, however, the striking features that two or more nano-scale particles with a cubic shape and a rod shape were aligned linearly along (100) directions were observed on isothermal annealing at 873 K and 1073 K, respectively. To investigate electro-magnetic properties of precipitates in a Cu-Fe-Ni alloy, the superconducting quantum interference device (SQUID) magnetometer and physical property measurement system (PPMS) were also complemented. The present study revealed significant influences that the magnetic properties of the specimens were closely related to the microstructures in the Cu-Fe-Ni alloy, which microstructures significantly depend on the isothermal annealing temperature.

Magnetic, optical and structural property studies of Mn-doped ZnO nanosheets.

We report the synthesis of pure and Mn doped ZnO in the form of nanosheets using a simple and single step procedure involving a microwave assisted chemical method. As prepared Mn-doped ZnO nanosheets were characterized using X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), ultra violet-visible (UV-Vis), Raman spectroscopy and magnetization measurements. The structural studies using XRD and TEM revealed the absence of Mn-related secondary phases and showed that Mn-doped ZnO comprise a single phase nature with wurtzite structure. FESEM and TEM micrographs show that the average diameter of Mn-ZnO assembled nanosheets is about approximately 50 nm, and the length of a Mn-doped ZnO nanosheet building block which is made up of thin mutilayered sheets is around approximately 300 nm. Concerning the Raman scattering spectra, the shift in peak position of E2 (high) mode toward low frequencies due to the Mn doping could be explained well by means of the spatial correlation model. Magnetic measurements showed that Mn-doped ZnO nanosheets exhibit ferromagnetic ordering at or above room temperature.

Correction to: No prominent toxicity of polyethylene microplastics observed in neonatal mice following intratracheal instillation to dams during gestational and neonatal period.

[This corrects the article DOI: 10.1007/s43188-020-00086-7.].

Efficacy and safety evaluation of adjuvant auricular acupuncture for smoking cessation: A study protocol of randomized, assessor-blinded, pragmatic pilot trial.

BACKGROUND: Smoking negatively impacts public health. There are several treatments to quit smoking, and nicotine replacement treatment (NRT) reportedly doubles the smoking cessation rate, with some limitations. Acupuncture is an alternative option with proven effects on smoking cessation. However, there has been no definite report that indicates the efficacy and safety of auricular acupuncture (AA) combined with NRT on smoking cessation. METHODS: This is a randomized, assessor-blind, and pragmatic pilot study. We will recruit 40 participants who want to stop smoking and randomly allocate them into an NRT group and an NRT + AA group with a 1:1 ratio. Participants will receive NRT for 4 weeks and the NRT + AA group will receive additional AA treatment with 5 AA points (Shenmen (TF4), lung (CO14), throat (TF3), inner nose (TG4), and endocrine (CO18)) twice a week for 4 weeks. Follow-up will be conducted 1 and 3 months after intervention completion. The primary outcome will be tobacco consumption and abstinence rate determined by calculating the rate of change in cigarette use and a urine test. Secondary outcomes will be the quality of life (EuroQol-5D and visual analogue scale), nicotine dependence (Fagerstrom test for nicotine dependence), nicotine withdrawal (Minnesota nicotine withdrawal scale), physical effects, satisfaction, and safety measurement (adverse events). RESULTS: We will investigate the efficacy and safety of AA combined with NRT treatment for smoking cessation. CONCLUSION: Our study will provide additional clinical evidence for AA as an adjuvant treatment for smoking cessation. TRIAL REGISTRATION NUMBER: Clinical Research Information Service (registration number: KCT0007212).

Structural and magnetic study of a diluted magnetic semiconductor: Fe-doped CeO2 nanoparticles.

This paper reports the effect of Fe doping on the structure and room temperature ferromagnetism of CeO2 nanoparticles. X-ray diffraction and the selective area electron diffraction measurements performed on the Ce(1-x)Fe(x)O2 (0 < or = x < or = 0.07) nanoparticles showed a single-phase nature with a cubic structure, and none of the samples showed the presence of any secondary phase. The mean particle size, which was calculated using transmission electron microscopy, increased with the increase in the Fe content. The DC magnetization measurements that were performed at room temperature showed that all the samples exhibited ferromagnetism. The saturation magnetic moment increased with the increase in the Fe content.

Neoline Improves Memory Impairment and Reduces Amyloid-ß Level and Tau Phosphorylation Through AMPK Activation in the Mouse Alzheimer's Disease Model.

BACKGROUND: Alzheimer's disease (AD) is the most general, chronic, and progressive neurodegenerative senile disorder characterized clinically by progressive cognitive deterioration and memory impairment. Neoline is effective against neuropathic pain models, but the effects of neoline against AD-like phenotypes have not been investigated. OBJECTIVE: We offer the investigation of the effects of neoline in AD. METHODS: In this study, a Tg-APPswe/PS1dE9 AD mouse model was treated orally with neoline at a concentration of 0.5 mg/kg or 0.1 mg/kg starting at 7.5 months and administered for three months, and its anti-AD effects were evaluated. RESULTS: Neoline improved memory and cognition impairments and reduced the number of amyloid-beta plaque and the amount of amyloid-ß in the brain of AD mice. Furthermore, neoline reduced the anxiety behavior in the AD mouse model. The chronic administration of neoline also induced AMPK phosphorylation and decreased tau, amyloid-ß, and BACE1 expression in the hippocampus. These findings indicate that chronic administration of neoline has therapeutic effects via AMPK activation, and BACE1 downregulation resulted in a decrease in the amyloid-ß levels in the brain of Tg-APPswe/PS1dE9 AD mice. CONCLUSION: Our results suggest that neoline is a therapeutic agent for the cure of neurodegenerative diseases like AD.

No prominent toxicity of polyethylene microplastics observed in neonatal mice following intratracheal instillation to dams during gestational and neonatal period.

Microplastics (MPs) have been recently recognized as a global environmental threat and its exposure as a risk factor to human health. Health effects through MPs exposure have been recently reported, especially through oral route of exposure. Since MPs could be exposed to humans through routes other than oral, this study was designed to evaluate whether MPs exposed through the inhalation route could be delivered to fetal mice and exhibit systemic toxicity. Polyethylene (PE) with 10-45 µm diameter were administered at 0 (distilled water, vehicle control), 6 (low administration), and 60 (high administration) µg/mouse/day to 3 pregnant dams per group from gestational day 9 to postnatal day (PND) 7 through intratracheal instillation. Dams and neonates were sacrificed at PND 7 and blood was collected. Various neonatal organs including brain, lung, heart, stomach, intestine, kidneys, and ovaries were collected for histopathological observation and weight measurement. No influence of PE-MPs administration was observed on the number of offsprings born, but the body and organs' weight were heavier overall in the high administration group of dams and neonates than the other groups with statistical significance achieved in the heart and spleen weight. Level of serum acetylcholinesterase and glutathione peroxidase activity was decreased in the high administration group of dams and neonates compared with the other groups. Lung was the organ with highest number of PE-MPs present in the both administration groups of dams, and PE-MPs were also detected in liver and intestine of the high administration dams. Whereas, PND7 neonates showed accountable numbers of PE-MPs only in kidneys of the high administration group. Overall, the present study indicates that PE-MPs instilled intratracheally could be delivered to neonates from dams. Even though adverse effects from PE-MPs exposure during pregnant and lactational period are less prominent on both dam and neonate, potential of second-generation toxicity could be considered for further investigation.

Effectiveness, Cost-Utility, and Safety of Neurofeedback Self-Regulating Training in Patients with Post-Traumatic Stress Disorder: A Randomized Controlled Trial.

Post-traumatic stress disorder (PTSD) is characterized by neurophysiological and psycho-emotional problems after exposure to trauma. Several pharmacological and psychotherapy limitations, such as adverse events and low adherence, increase the need for alternative therapeutic options. Neurofeedback is widely used for PTSD management. However, evidence of its clinical efficacy is lacking. We conducted a randomized, waitlist-controlled, assessor-blinded clinical trial to assess the effectiveness, cost-utility, and safety of 16 sessions of neurofeedback on people with PTSD for eight weeks. Eleven participants were allocated to each group. One and two subjects dropped out from the neurofeedback and control groups, respectively. The primary outcome was PTSD symptom change evaluated using the PTSD Checklist-5 (PCL-5-K). The PCL-5-K levels improved more in the neurofeedback group (44.3 ± 10.8 to 19.4 ± 7.75) than in the control group (35.1 ± 18.5 to 31.0 ± 14.92). The change value was significantly improved in the neurofeedback group (24.90 ± 13.13 vs. 4.11 ± 9.03). Secondary outcomes such as anxiety, depression, insomnia, and quality of life were also improved. In an economic analysis using EuroQol-5D, the incremental cost-per-quality-adjusted life-year was approximately $15,600, indicating acceptable cost-utility. There were no adverse events in either group. In conclusion, neurofeedback might be a useful, cost-effective, and safe intervention for PTSD management.

Patterns of Integrative Korean Medicine Practice for Anxiety Disorders: A Survey among Korean Medicine Doctors (KMDs) in Korea.

Anxiety disorder is known as the most common disease among psychiatric disorders. However, many studies have not been conducted in the Korean medicine area. This study explores the current state of anxiety disorder treatments of Korean medicine through a survey research. The survey for Korean medicine doctors (KMDs) on Korean medicine (KM) diagnosis and treatments for anxiety disorder was conducted online from December 21, 2016, to December 29, 2016. The results were divided into two groups, KMDs and Korean medicine neuropsychiatric specialists (KMNPS), and comparatively analyzed. Self-evaluation and counseling were the most common in both diagnostic methods and evaluation of treatment effects, and KMNPS tended to make extensive use of objective indicators. There was no difference in the rate of psychiatric medication use among the patients between KMD and KMNPS. The main reason for patients wanting KM treatment was the tapering cessation of psychiatric medications. The most common treatments were acupuncture, herbal medicine, and moxibustion, in addition to dry cupping in KMD and psychotherapy in KMNPS. The most important factor for treatment was herbal medicine treatment, followed by rapport formation in KMD and patient's temperament in KMNPS. Opinions on various items were presented as treatment barriers, and KMNPS tended to think more importantly about the patient's family problems. For the items to be additionally trained in the future, KMD chose the diagnostic tools and KMNPS chose psychotherapies. This study is the first study to analyze the clinical patterns for anxiety disorder in KMDs. KMD and KMNPS showed similar patterns in the perception, diagnosis, and treatment of anxiety disorders, but KMNPS tended to use objective indicators and psychotherapy more actively. Further clinical studies for the development of clinical guidelines should be additionally required.

Neurofeedback self-regulating training in patients with Post traumatic stress disorder: A randomized controlled trial study protocol.

BACKGROUND: Post-traumatic stress disorder (PTSD) has become an important public health problem. However, the conventional therapeutic strategy, including pharmacotherapy and cognitive behavioral therapy, has limitations. Neurofeedback is a technique that utilizes electroencephalography (EEG) signaling to monitor human physiological functions and is widely used to treat patients with PTSD. The purpose of our study is to assess the efficacy and safety level of neurofeedback treatment in patients with PTSD using quantitative EEG. METHODS: This is a randomized, waitlist-controlled, assessor-blinded, clinical trial. Forty-six patients with PTSD will be randomly assigned at a 1:1 ratio into two groups. The participants in the treatment group will receive neurofeedback treatment for 50 min, twice a week, for 8 weeks (16 sessions). Quantitative EEG will be utilized to monitor the physiological functions and brain waves of the participants. A four-week follow-up period is planned. The participants in the control group will wait for 12 weeks. The primary outcome is the Korean version of PTSD Checklist-5 (PCL-5-K) score. The PCL-5-K scores on week 8 will be compared between the two groups. Anxiety, depression, insomnia, emotions, EEG, quality-of-life, and safety level will be assessed as secondary outcomes. DISCUSSION: This trial will describe a clinical research methodology for neurofeedback in patients with PTSD. The numerous subjective and objective secondary outcomes add to the value of this trial's results. It will also suggest a therapeutic strategy for utilizing quantitative EEG in patients with PTSD. Our trial will provide basic evidence for the management of PTSD via an integrative treatment. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT0003271.

Acupuncture for anxiety: A protocol for a systematic review of controlled trials.

BACKGROUND: Acupuncture has been widely, used in Asian countries since the Yuan Dynasty in China. Moreover, acupuncture has been reported to exhibit anti-allergy effects in many clinical trials. This systematic review will assess the effectiveness, and safety of acupuncture for anxiety treatment. METHODS: Eleven databases, including Asian databases, will be searched for studies conducted through December in the year 2017. We will include randomized controlled trials (RCTs) assessing acupuncture for anxiety. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. It will also be disseminated electronically, and in print. The review will be updated to inform, and guide healthcare practices. REGISTRATION NUMBER: PROSPERO 2018 under number CRD42018080034.

Effectiveness of collaborative treatment using Korean and Western medicine for mild cognitive impairment or dementia: A protocol for a prospective observational exploratory study.

BACKGROUND: South Korea has a dual medical system comprising conventional Western medicine (WM) and traditional Korean medicine (KM), which has yielded both positive results (increased opportunity to choose medical care) and negative results (increased medical costs). Thus, the Ministry of Health and Welfare has been performing a pilot project to evaluate this collaborative system in the real clinical situation. As treatment of dementia requires a social approach, the Korean government aims to strengthen the role of the national health care system to reduce the burden of dementia. The aim of this study was to evaluate the clinical - and cost-effectiveness of collaborative KM and WM treatment in patients with dementia or mild cognitive impairment (MCI) in Korea. METHOD/DESIGN: In total, 180 patients with dementia or MCI will be recruited and will undergo monthly check-up for 12 weeks. Information regarding demographic characteristics, baseline disease-related data, and outcomes related to cognitive function and quality of life will be obtained. For data analysis, the patients will be classified into 2 groups using a comparative observational study design: the sole treatment group, which will receive either WM or KM alone, and the collaborative treatment group, which will receive both WM and KM. DISCUSSION: The treatment of dementia/MCI in South Korea will be studied in the real world during the pilot project. There will be no limitations on the type of treatment or the specific treatment method. Examining the clinical- and cost- effectiveness of the different methods will supply information for building an optimal medical system for the treatment of dementia/MCI. TRIAL REGISTRATION: The protocol for this study has been registered at the clinical research information service (CRIS: KCT0002868).

Illite improves memory impairment and reduces Aß level in the Tg-APPswe/PS1dE9 mouse model of Alzheimer׳s disease through Akt/CREB and GSK-3ß phosphorylation in the brain.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of illite in Korean medicine has a long history as a therapeutic agent for various cerebrovascular diseases. According to Dongui Bogam, illite can be used for Qi-tonifying, phlegm dispersing and activation of blood circulation which is an important principle for the treatment of brain-associated diseases. AIM OF THE STUDY: This study was undertaken to evaluate beneficial effects of illite on the neurodegenerative diseases such as Alzheimer׳s disease (AD). MATERIAL AND METHODS: The transgenic mice of AD, Tg-APPswe/PS1dE9, were fed with 1% or 3% of illite for 3 months. Behavioral, immunological and ELISA analyses were used to assess memory impairment with additional measurement of Aß accumulation and plaque deposition in the brain. Other in vitro studies were performed to examine whether illite inhibits the Aß-induced neurotoxicity in human neuroblastoma cell line, SH-SY5Y cells. RESULTS: Illite treatment rescued Aß-induced neurotoxicity on SH-SY5Y cells, which was dependent on the PI3K/Akt activation. Intake of illite improved the Aß-induced memory impairment and suppressed Aß levels and plaque deposition in the brain of Tg-APPswe/PS1dE9 mice. Illite increased CREB, Akt, and GSK-3ß phosphorylation and suppressed tau phosphorylation in the AD-like brains. Moreover, 1% of illite reduced weight gain and suppressed glucose level in the blood. CONCLUSION: The present study suggests that illite has the potential to be a useful adjunct as a therapeutic drug for the treatment of AD.

Alteration in brain-derived neurotrophic factor (BDNF) after treatment of mice with herbal mixture containing Euphoria longana, Houttuynia cordata and Dioscorea japonica.

BACKGROUND: Literature data indicate that brain-derived neurotrophic factor (BDNF), cyclic-AMP response element-binding protein (CREB) and phospho-CREB (pCREB) may have a place in depression. BDNF belongs to the neurotrophin family that plays an important role in proliferation, survival and differentiation of different cell populations in the mammalian nervous system. The herbal mixture used in the present study consists of Euphoria longana, Houttuynia cordata and Dioscorea japonica. The purpose of the present study was to determine the neuroprotective effect of herbal mixture. We also tested the hypothesis that administration of herbs reverses memory deficits and promotes the protein expression of BDNF in the mouse brain. METHODS: Mice were randomized into four different treatment groups (n = 10/group). Normal and stress groups received regular lab chow without stress and under stress conditions, respectively, for 3 weeks. The animals in the stress group were immobilized for 4 hours a day for 2 weeks. Different doses of herbal mixture (206 and 618 mg/kg) were administered for 3 weeks to those mice under stress conditions. Mice were analyzed by behavioral tests and immunoblotting examination in the hippocampus and cortex. An additional in vitro investigation was performed to examine whether herbs induce neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells. RESULTS: No significant toxicity of herbs on human neuroblastoma cells was observed. These herbs demonstrated an inductive effect on the expression of BDNF, pCREB and pAkt. For spatial working memory test, herbal mixture fed mice exhibited an increased level of spontaneous alternation (p < 0.01) compared to those in stress conditions. Moreover, herbal mixture produced highly significant (p < 0.01) reduction in the immobility time in the tail suspension test. Mice in the herbal mixture groups demonstrated lower serum corticosterone concentration than mice in the stress group (p < 0.05). Effects of the oral administration of herbal mixture on protein levels of BDNF in the hippocampi and cortices were significant. CONCLUSIONS: Our study showed that herbal mixture administration has antidepressant effects in mice. It is proposed that adverse events such as stress and depression can modulate the expression of molecular players of cellular plasticity in the brain.

Value and Safety of Midazolam Anesthesia during Transrectal Ultrasound-Guided Prostate Biopsy.

PURPOSE: Although transrectal ultrasound-guided prostate biopsy is useful for diagnosing prostate cancer, it is a painful procedure. There are many methods for providing pain relief and for treating discomfort during the procedure, but occasionally these are reported to be of limited use. We aimed to evaluate the value and safety of midazolam-induced anesthetic transrectal ultrasound-guided prostate biopsy. MATERIALS AND METHODS: From August 2008 to December 2009, 104 male patients, who were examined with transrectal ultrasound-guided prostate 12-core biopsy, were randomly assigned to two groups. Group 1 (n=51) received ketorolac (Tarasyn®) 30 mg. Group 2 (n=53) was treated with midazolam (Dormicum®) 3 mg, which was increased to 5 mg if necessary. Immediately after the procedure, the patients were asked to rate their comfort level by using a 10-point visual analog self-assessment pain scale. RESULTS: The pain scale in group 2 was significantly lower than that in group 1 (p<0.05). The patients assigned to group 2 experienced no side-effects from midazolam and were more satisfied than the patients in group 1 (p<0.05). CONCLUSIONS: Midazolam anesthesia relieves pain effectively, and the patient's satisfaction is better than with conventional transrectal ultrasound-guided prostate biopsy. Midazolam-induced anesthetic transrectal ultrasound-guided prostate biopsy is useful and safe.