Cognitive Behavioral Therapy for Migraine Headache: A Systematic Review and Meta-Analysis.

Background and Objectives: Migraine headaches are chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. Materials and Methods: Seven electronic databases were searched from the date of inception to December 2020. Randomized controlled studies (RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on Visual Analog Scale (VAS), the frequency of drug use, Migraine Disability Assessment (MIDAS), and Headache Impact Test (HIT-6) index. The two authors independently conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. Results: Among the 373 studies, 11 RCTs were included in this systematic review. Seven out of the 11 RCTs were conducted in the USA, and four were conducted in the UK, Germany, Iran, and Italy, respectively. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache strength was significantly reduced. Two of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. Conclusions: CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis and headache intensity subgroup analysis, with few adverse events. Additional RCTs with CBT for migraine headaches are needed for a more accurate analysis.

Production of CaCO3-single-coated probiotics and evaluation of their spectroscopic properties, morphological characteristics, viability, and intestinal delivery efficiency.

The intake of probiotics offers various health benefits; however, their efficacy depends on the maintenance of viability during industrial processing and digestion. Probiotic viability can be compromised during encapsulation, freeze-drying, storage, and digestion, necessitating multiple coatings. This complicates production and raises costs. In this study, CaCO3-single-coated probiotics (CSCPs) were prepared, an approach rarely reported before. Through instrumental analyses, the encapsulation of probiotics within CaCO3 was confirmed, ensuring their high viability. This proposed technology effectively preserves the viability of probiotics during the encapsulation and freeze-drying processes, resulting in minimal cell loss. Moreover, CSCPs demonstrated exceptional viability performance under simulated gastric and intestinal conditions. Notably, 100% of these microorganisms reached the intestines, delivering over 10 billion CFUs of probiotics in a viable state. This study highlights the potential of CSCPs as a feasible solution for overcoming probiotic encapsulation challenges and optimizing therapeutic benefits.

Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study.

Introduction: The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality. Methods: Forty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed. Results: No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group. Conclusion: These results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine. Clinical trial registration: https://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.

Molecular beacon-based quantitiation of epithelial tumor marker mucin 1.

Mucin 1 (Muc1) is a glycoprotein expressed on most epithelial cell surfaces, which has been confirmed as a useful biomarker for the diagnosis of early cancers. In this study, we demonstrate that a quantum dot (QD)-aptamer beacon acts by folding-induced dissociation of a DNA intercalating dye, BOBO-3, in the presence of the target molecules, Muc1. Release of intercalated BOBO-3s from the QD-conjugated aptamers results in a decrease in QD fluorescence resonance energy transfer (FRET)-mediated BOBO-3 emission, allowing for label-free Muc1 detection and quantitation. We attain highly specific and wide-range detection (from 50nM to 20µM) of Muc1, suggesting that our QD-aptamer beacon can be a potential alternative to immuno-based assays for Muc1 detection. The detection methodology is expected to be improved for the early diagnosis of different types of epithelial cancers of large populations.

The efficacy and safety of yukmijihwang-hwan (Liuweidihuang-wan) for type 2 diabetes mellitus without complications: A protocol for systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis of randomized controlled trials (RCTs) will aim to assess the efficacy and safety of Yukmijihwang-hwan for type 2 diabetes without complications. METHODS: To identify eligible studies, we will perform a systematic search of the following electronic databases: MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by NII, Korean Information Service System, Korean Medical Database, Oriental Medicine Advanced Searching Integrated System, and ScienceON. Search terms will include "Type 2 Diabetes" for participants as well as "Yukmijihwang-tang" or "Liuwei dihuang tang" for interventions. Two independent researchers will perform data extraction and assessment using Cochrane's risk of bias tool, with disagreements being resolved through discussions with a third researcher. RESULTS: This study will evaluate the antidiabetic effects of Yukmijihwang-hwan from 3 perspectives (blood glucose level, insulin resistance, and ß-cell function) as well as its safety by reviewing the reported adverse effects. CONCLUSION: This systematic review will provide evidence regarding the antidiabetic efficacy and safety of Yukmijihwang-tang in type 2 diabetes mellitus.

Efficacy of Geumguesingi-hwan (jinkuishenqi-wan, kinkijinki-gan) in decreasing blood glucose levels in patients with uncomplicated type 2 diabetes: A protocol for systematic review and meta-analysis.

BACKGROUND: The purpose of a systematic review and meta-analysis is to verify the clinical efficacy and safety of Geumguesingihwan for patients with uncomplicated type 2 diabetes. METHODS: The systematic review and meta-analysis will be performed following the guidelines of the National Evidence-based Healthcare Collaborating Agency. We will conduct a systematic search of randomized controlled trials in 8 electronic databases until August 31, 2021. RESULTS: This study will provide evidence regarding the clinical efficacy of Geumguesingi-hwan from the following 3 perspectives: improving blood glucose level, insulin resistance, and ß-cell function. Additionally, we will examine the safety of Geumguesingi-hwan by evaluating the adverse effects. CONCLUSIONS: This study will verify the antidiabetic efficacy and safety of Geumguesingi-hwan in patients with uncomplicated type 2 diabetes.

Detection of single-base mutation in RNA using T4 RNA ligase-based nick-joining or DNAzyme-based nick-generation.

A single nucleotide polymorphism (SNP) is a common genetic variation when a single nucleotide differs between members of a species or paired chromosome. Due to its association with disease susceptibility and drug resistance, SNP detection is of great value in studying the variation in drug responses. Here we present two quantitative SNP detection methods for a single-base mismatch in RNA, based on nick-joining and nick-generating activities of T4 RNA ligase and DNAzyme, respectively. T4 RNA ligase successfully discriminated a one-base mismatch in the ligation junction, and the designed DNAzyme cleaved RNA by discerning a single-base mismatch in the cleaving site.

An alternative to Western blot analysis using RNA aptamer-functionalized quantum dots.

To make full use both of optical properties of quantum dots (QDs) and of specific interactions between aptamers and their ligands of interest, we employed QD-conjugated RNA aptamer interactions with histidine tag. QDs offer revolutionary fluorescence performance due to their long-term photostability, brilliant colors, fixability, and narrow, symmetrical emission spectra, and aptamers are known to specifically bind to their target molecules, including metal ions, small molecules, and macromolecules. In this study, we have synthesized RNA aptamer-functionalized QDs, and demonstrated their application to specific protein detection, as an alternative to the conventional Western blot analysis. We observed that our RNA aptamer-functionalized QD system dramatically reduced the time and effort required for conventional Western blot analysis, whereas the selectivity was comparable to that of the conventionally available anti-histidine tag antibody and the sensitivity was comparable to that of the Coomassie blue staining method. In principle, owing to the remarkable optical properties of QDs and a wide versatility of aptamers for selection, our system can harness the high brightness, stability and reusability to quantitatively detect aptamer-recognizable proteins. Furthermore, multiplex detection for several proteins on a single blot can be achieved by our new method, which thus may be able to facilitate and simplify the routinely used protein detection procedure, and make a variety of proteomics analysis possible.

Efficacy and safety of HT048 and HT077 for body fat and weight loss in overweight adults: A study protocol for a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The prevalence of excessive body weight has rapidly increased worldwide over the past decades; however, medications are intended for moderately and severely obese patients and are associated with side effects. As an alternative approach, the use of traditional herbal medicines has gained increasing popularity among overweight individuals in recent years in East Asia. HT048 is an herbal extract of Citrus unshiu and Crataegus pinnatifida, and HT077 is an herbal extract of Nelumbo nucifera and Prunus persica. These 4 herbs have been used widely for body weight reduction in China and Korea. The aims of this trial are to investigate whether HT048 and HT077 are effective at reducing body fat and weight in overweight adults, and to determine the safety of HT048 and HT077. METHODS/DESIGN: A double-blind, randomized, placebo-controlled, 3-arm parallel group trial will be conducted in adults with a body mass index (BMI) of 25 to <30 kg/m. A total of 120 eligible participants will be randomized in a 1:1:1 ratio to receive either HT048 (1000 mg), HT077 (400 mg), or matching placebo twice daily for 12 weeks, and will be monitored for an additional 4-week follow-up period after the treatment. All participants will be assessed for efficacy and safety of the investigational product at baseline and weeks 4, 8, 12, and 16. The primary endpoint is the change in body fat mass and percent body fat measured by dual-energy X-ray absorptiometry at week 12 from the baseline. The secondary efficacy variables are abdominal fat area measured by computed tomography, body fat mass and percent body fat measured by bioelectrical impedance analysis, body weight, BMI, and serum lipids and adipocytokines concentrations. Safety will be evaluated on the basis of reported adverse events, abnormal laboratory results, vital signs, and physical examination findings. DISCUSSION: This is a first-in-human trial of HT048 and HT077 to assess the efficacy and safety in overweight subjects. The results will provide high-quality evidence of the therapeutic benefits of HT048 and HT077 for weight management and the prevention of obesity. TRIAL REGISTRATION: Korean Clinical Research Information Service (KCT0004271) Registered September 2, 2019.

Sniffing for gene-silencing efficiency of siRNAs in HeLa cells in comparison with that in HEK293T cells: correlation between knockdown efficiency and sustainability of sirnas revealed by FRET-based probing.

Investigation of the intracellular fate of small interfering RNAs (siRNAs) following their delivery into cells is of great importance to elucidate their dynamics in cytoplasm. Here we describe the use of an advanced fluorescence-based method to probe the dissociation and/or degradation of double-labeled siRNAs in HeLa cells in comparison with that in human embryonic kidney 293T (HEK293T) cells. This work was performed with three siRNAs labeled with fluorescence resonance energy transfer (FRET) dyes, allowing a non-destructive and non-invasive assessment of the dissociation and degradation state of siRNAs in cultured cells. Our FRET analysis not only shows the asymmetric degradation as well as the time-dependent dissociation of each siRNA strand during the measured time period, underlining the high intrinsic nuclease resistance of duplex siRNAs, but also reveals the longer sustainability of siRNAs in HeLa cells compared with that in HEK293T cells, explaining the gene silencing in HeLa cells is more efficient than that in HEK293T cells. In addition, our single-molecule FRET assays demonstrate the potential of the delineated fluorescence-based technique for future research on biological behavior of siRNAs even at the single-molecule level. The fluorescence-based method is a straightforward technique to gain direct information on siRNA integrity inside living cells, which can provide a detection tool for dynamics of biological molecules.

FRET-based probing to gain direct information on siRNA sustainability in live cells: Asymmetric degradation of siRNA strands.

Investigation of the intracellular fate of small interference RNA (siRNA) following their delivery into cells is of great interest to elucidate dynamics of siRNA in cytoplasm. However, its cellular delivery and sustainability should be understood at the molecular level and improved for the successful in vivo application of siRNA. Here we present a fluorescence resonance energy transfer (FRET) based method using oligonucleotide probes to study intracellular dissociation (or melting) and sustainability of siRNAs in live cells. The FRET probes were specifically designed to observe intracellular dissociation (or melting) and degradation of short synthetic RNAs in real-time, thus providing the desired kinetic information in cells. Intracellular FRET analysis shows that siRNA duplex is gradually diffused into cytosol, dissociated, and degraded for a duration of 3.5 h, which is confirmed by confocal microscopy colocalization measurements. In addition, our FRET assays reveal the asymmetric degradation as well as the time-dependent dissociation of each siRNA strand. The application of this FRET technique can allow for direct information on siRNA integrity inside living cells, providing a detection tool for dynamics of biological molecules.