Anti-Wrinkle and Skin Moisture Efficacy of 7-MEGATM: A Randomized, Double-Blind, Placebo Comparative Clinical Trial.

7-MEGATM is a food product made from purified Alaska pollack fish oil containing palmitoleic acid (16:1), commonly referred to as omega-7. We sought to quantitatively evaluate whether this substance inhibits skin aging. A total of 101 middle-aged females were randomly allocated to the intervention (N = 50) or placebo group (N = 51). Each participant was advised to take either 500 mg of 7-MEGATM or a placebo twice daily for 12 weeks. The primary outcomes were the degree of improvement in wrinkles and the degree of moisture filling after consumption for 12 weeks compared to baseline. The secondary outcomes were improvement in skin wrinkles; moisture changes at 4 and 8 weeks from baseline; changes in transdermal water loss, skin elasticity, the melanin index, the erythema index, and the Global Photo Damage Score. We found a significant improvement in skin wrinkles and elasticity at 12 weeks in the 7-MEGATM-consuming group compared to that in the placebo group; skin moisture, elasticity, and the melanin index were also improved. No supplement-related adverse reactions were observed and 7-MEGATM was identified as safe. 7-MEGATM was effective for human skin function in terms of wrinkles, moisture, elasticity, and melanin production and may be useful as a skin nutritional supplement.

The anti-obesity effect of mulberry leaf (Mori Folium) extracts was increased by bioconversion with Pectinex.

Mulberry leaf (Mori Folium) extract (MLE) is known to have anti-obesity effects. In this study, the enhanced effects of MLE after bioconversion treatment using Pectinex (BMLE) on obesity were explored, and the underlying mechanisms were investigated using the active components, neochlorogenic acid (5-CQA) and cryptochlorogenic acid (4-CQA), whose amounts were increased by bioconversion of MLE. Both MLE and BMLE inhibited lipid accumulation in 3T3-L1 adipocytes without cytotoxicity and suppressed the expression of CCAAT/enhancer-binding protein alpha (C/EBPα). In addition, MLE and BMLE decreased high-fat diet-induced adipose tissue mass expansion. Notably, BMLE significantly increased antiadipogenic and anti-obesity effects compared to MLE in vitro and in vivo. The active ingredients increased by bioconversion, 5-CQA and 4-CQA, inhibited the protein levels of C/EBPα and the mRNA levels of stearoyl-CoA desaturase 1 (Scd1). These findings provide new insights into the therapeutic possibility of using bioconversion of MLE, by which upregulation of 5-CQA and 4-CQA potently inhibits adipogenesis.

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.

A rare case of numerous thoracolithiasis with chest discomfort.

Thoracolithiasis is a rare benign condition with mobile free bodies in the pleural cavity. It is asymptomatic and mostly found incidentally. Up to our knowledge there is no report of symptomatic numerous thoracolithiasis. We report a very rare case of thoracolithiasis in a 36-year-old female with chest discomfort. Images from computed tomography presented a chain of small non-enhancing nodules in the left hemi-diaphragmatic pleura. Exploratory thoracoscopy was performed and twenty-five mobile pearl like thoracolithiasis were discovered. Histopathology showed extensive necrotic fatty tissue at its center surrounded by fibrosis. The patient was symptom-free after the surgical removal of numerous thoracolithiasis, suggesting thoracolithiasis was associated with chest discomfort.

Radiometallic Complexes of DO3A-Benzothiazole Aniline for Nuclear Medicine Theranostics.

To develop a radioactive metal complex platform for tumor theranostics, we introduced three radiopharmaceutical derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid-benzothiazole aniline (DO3A-BTA, L1) labeled with medical radioisotopes for diagnosis (68Ga/64Cu) and therapy (177Lu). The tumor-targeting ability of these complexes was demonstrated in a cellular uptake experiment, in which 177Lu-L1 exhibited markedly higher uptake in HeLa cells than the 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex. According to in vivo positron emission tomography imaging, high accumulation of 68Ga-L1 and 64Cu-L1 was clearly visualized in the tumor site, while 177Lu-L1 showed therapeutic efficacy in therapy experiments. Consequently, this molecular platform represents a useful approach in nuclear medicine toward tumor-theranostic radiopharmaceuticals when 68Ga-L1 or 64Cu-L1 is used for diagnosis, 177Lu-L1 is used for therapy, or two of the compounds are used in conjunction with each other.

Ipsilateral pleural recurrence after diagnostic transthoracic needle biopsy in pathological stage I lung cancer patients who underwent curative resection.

OBJECTIVES: The relationship between transthoracic needle biopsy (TTNB) and pleural recurrence of cancer after curative lung resection remains unclear. We aimed to assess whether TTNB increases the ipsilateral pleural recurrence (IPR) rate and identify other potential risk factors for pleural recurrence after surgery. MATERIALS AND METHODS: This retrospective study included 392 patients with p-stage I non-small cell lung cancer with solid or part-solid nodules after curative lung resection in 2009-2010. Imbalances among the characteristics were adjusted using an inverse probability-weighted method based on propensity scoring. Multivariate Cox's regression analysis and the Kaplan-Meier method were used to determine independent risk factors for IPR. RESULTS: A total of 243 (62%) patients received TTNB, while 149 (38%) underwent an alternate, or no, diagnostic technique. IPR was significantly more frequent in the TTNB group (p=0.004), while total recurrence was similar between the groups (p=0.098). After applying the weighted model, diagnostic TTNB (hazard ratio [HR], 5.27; 95% confidence interval [CI], 1.49-18.69; p=0.010), microscopic visceral pleural invasion (HR, 2.76; 95% CI, 1.08-7.01; p=0.033) and microscopic lymphatic invasion (HR, 3.25; 95% CI, 1.30-8.10; p=0.012) were associated with an increased frequency of IPR. Among patients who received TTNB, microscopic lymphatic invasion was a risk factor for IPR (HR, 2.74; 95% CI, 1.10-6.79; p=0.030). CONCLUSIONS: The diagnostic TTNB procedure is associated with pleural recurrence but may be unrelated to overall recurrence-free survival in early lung cancer. Moreover, microscopic lymphatic invasion could be a risk factor for pleural recurrence. TTNB should be carefully considered before lung resection and close follow-up to detect if pleural recurrence is needed.

Gadolinium Complex of 1,4,7,10-Tetraazacyclododecane-1,4,7-trisacetic Acid (DO3A)-Ethoxybenzyl (EOB) Conjugate as a New Macrocyclic Hepatobiliary MRI Contrast Agent.

We report the synthesis of a macrocyclic Gd chelate based on a 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) coordinationn cage bearing an ethoxybenzyl (EOB) moiety and discuss its use as a T1 hepatobiliary magnetic resonance imaging (MRI) contrast agent. The new macrocyclic liver agent shows high chelation stability and high r1 relaxivity compared with linear-type Gd chelates, which are the current clinically approved liver agents. Our macrocyclic, liver-specific Gd chelate was evaluated in vivo through biodistribution analysis and liver MRI, which demonstrated its high tumor detection sensitivity and suggested that the new Gd complex is a promising contrast agent for liver cancer imaging.

Manganese Complex of Ethylenediaminetetraacetic Acid (EDTA)-Benzothiazole Aniline (BTA) Conjugate as a Potential Liver-Targeting MRI Contrast Agent.

A novel manganese(II) complex based on an ethylenediaminetetraacetic acid (EDTA) coordination cage bearing a benzothiazole aniline (BTA) moiety (Mn-EDTA-BTA) was designed and synthesized for use as a liver-specific MRI contrast agent with high chelation stability. In addition to forming a hydrophilic, stable complex with Mn2+, this new Mn chelate was rapidly taken up by liver hepatocytes and excreted by the kidneys and biliary system. The kinetic inertness and R1 relaxivity of the complex were much higher than those of mangafodipir trisodium (MnDPDP), a clinically approved liver-specific MRI contrast agent. The diagnostic utility of this new Mn complex in MRI was demonstrated by high-sensitivity tumor detection in an animal model of liver cancer.

Gadolinium Nanoparticles Conjugated with Therapeutic Bifunctional Chelate as a Potential T1 Theranostic Magnetic Resonance Imaging Agent.

This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponding low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B.

Synthesis, Magnetic Properties, Map Images, and Water Proton Relaxivities of D-Glucuronic Acid Coated Ln2O3 Nanoparticles (Ln = Ho and Er).

T2 MRI contrast agents cannot be synthesized by using molecules but nanoparticles because appreciable magnetic moments at room temperature are needed. Recently, some of lanthanide (Ln) oxide nanoparticles have shown decent magnetic moments at room temperature and even at ultrasmall particle diameters. In this study, we explored D-glucuronic acid coated Ln2O3 nanoparticles (Ln = Ho and Er) with ultrasmall particle diameters. They showed decent magnetic moments at room temperature and as a result, appreciable transverse water proton relaxivities (r2s) at 1.5 tesla MR field. Clear dose-dependent contrast enhancements in R2 map images were observed in both samples. These results showed that D-glucuronic acid coated Ln2O3 nanoparticles (Ln = Ho and Er) would be potential T2 MRI contrast agents at high MR fields.

Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application.

A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+) ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

Characterization of gastrointestinal disorders in patients with parkinsonian syndromes.

OBJECTIVES: This study was aimed to investigate gastrointestinal (GI) dysfunction in patients with Parkinson's disease (PD) compared with those in patients with other parkinsonian disorders, and to characterize parkinsonian motor and non-motor correlates for GI dysfunction. METHODS: Consecutive patients with PD, atypical parkinsonism (P-plus) and vascular parkinsonism (VP) were enrolled in this multicenter systematic survey. Data for weight loss, appetite loss, sialorrhea, dysphagia, gastroesophageal reflux disease (GERD) and constipation were simultaneously collected using symptom-specific, structured questionnaires. For the PD group, information for onset age, PD duration, anti-parkinsonian drug dosages, unified PD rating scale, and Hoehn & Yahr stage were collected at the time of the interview. RESULTS: Enrolled in the study were 329 PD, 82 P-plus, and 62 VP patients. GI symptom frequencies were similar in PD and other parkinsonian groups. Among the PD patients, constipation was the most common symptom, followed by appetite loss, weight loss, dysphagia, sialorrhea, and GERD (64.9%, 45.4%, 35.7%, 19.4%, 15.0%, and 9.6%, respectively). Dysphagia, sialorrhea, and constipation became more frequent with more advanced PD stages. Cognition, sleep and mood disturbances were significantly associated with weight loss, appetite loss, and dysphagia, whereas bradykinesia, axial and postural instability with gait disturbance were associated with dysphagia. CONCLUSIONS: GI disturbance is common in patients with non-PD parkinsonism as well as in those with PD. GI symptoms correlated with distinct parkinsonian motor and nonmotor features in PD. Further studies are warranted to reveal the pathophysiological mechanisms and prognostic features of GI disturbances in parkinsonian disorders.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle.

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s(-1) mM(-1) and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies.

Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide.

Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

Cyclic RGD Peptides Incorporating Cycloalkanes: Synthesis and Evaluation as PET Radiotracers for Tumor Imaging.

Two new bicyclic arginine-glycine-aspartic acid (RGD) peptides, c(RGD-ACP-K) (1a) and c(RGD-ACH-K) (1b), incorporating the aminocyclopentane (ACP) and aminocyclohexane (ACH) carboxylic acids, respectively, were synthesized by grafting the aminocycloalkane carboxylic acids onto the tetra-peptide RGDK sequence. These peptides and their conjugates with DO3A (1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid) (2a-b) exhibit high affinity toward U87MG glioblastoma cells. Their affinity is greater than that exhibited by c(RGDyK). Labeling these conjugates with radiometal (64)Cu resulted in high radiochemical yields (>97%) of the corresponding complexes, abbreviated as c(RGD-ACP-K)-DOTA-(64)Cu (3a) and c(RGD-ACH-K)-DOTA-(64)Cu (3b). Both 3a and 3b are stable for 24 h in human and mouse serums and show high tumor uptake, as observed by positron emission tomography (PET). Blocking experiments with 3a and 3b by preinjection of c(RGDyK) confirmed their target specificity and demonstrated their promise as PET radiotracers for imaging ανß3-positive tumors.

Mixed lanthanide oxide nanoparticles as dual imaging agent in biomedicine.

There is no doubt that the molecular imaging is an extremely important technique in diagnosing diseases. Dual imaging is emerging as a step forward in molecular imaging technique because it can provide us with more information useful for diagnosing diseases than single imaging. Therefore, diverse dual imaging modalities should be developed. Molecular imaging generally relies on imaging agents. Mixed lanthanide oxide nanoparticles could be valuable materials for dual magnetic resonance imaging (MRI)-fluorescent imaging (FI) because they have both excellent and diverse magnetic and fluorescent properties useful for dual MRI-FI, depending on lanthanide ions used. Since they are mixed nanoparticles, they are compact, robust, and stable, which is extremely useful for biomedical applications. They can be also easily synthesized with facile composition control. In this study, we explored three systems of ultrasmall mixed lanthanide (Dy/Eu, Ho/Eu, and Ho/Tb) oxide nanoparticles to demonstrate their usefulness as dual T2 MRI-FI agents.

Surface coated Eu(OH)3 nanorods: a facile synthesis, characterization, MR relaxivities and in vitro cytotoxicity.

The water-soluble and biocompatible D-glucuronic acid coated Eu(OH)3 nanorods (average thickness x average length = 9.0 x 118.3 nm) have been prepared in one-pot synthesis. The D-glucuronic acid coated Eu(OH)3 nanorods showed a strong fluorescence at approximately 600 nm with a narrow emission band width. A cytotoxicity test by using DU145 cells showed that D-glucuronic acid coated Eu(OH)3 nanorods are not toxic up to 100 microM, making them a promising candidate for biomedical applications such as fluorescent imaging. The minimum Eu concentration needed for a conventional confocal imaging was estimated to be approximately 0.1 mM. Therefore, D-glucuronic acid coated Eu(OH)3 nanorods can be applied to fluorescent imaging. However, a very tiny magnetization of approximately 1.2 emu/g at room temperature and at an applied field of 5 tesla was observed. As a result, very small r1 and r2 water proton relaxivities were estimated, implying that surface coated Eu(OH)3 nanorods are not sufficient for MRI contrast agents.

Effect of carbon black materials on the electrochemical properties of sulfur-based composite cathode for lithium-sulfur cells.

To investigate the effect of the electrode materials on the electrochemical performance of Li-S cells, sulfur cathodes were constructed using four types of carbon blacks: Ketjenblack EC-600JD (KB-600), Printex XE-2, Cabot BP-2000, and Super-P. It was found that the electrochemical performance of sulfur cathode was strongly dependent on the type of carbon black used. In the first discharge, the sulfur cathodes containing carbon blacks with a high surface area, KB-600 (SBET = 1270 m2/g), Printex XE-2 (SBET = 950 m2/g), or Cabot BP-2000 (SBET = 1487 m2/g), showed much higher discharge capacities (>1200 mA h/g) than the sulfur cathode (710 mA h/g) with Super-P (SBET = 62 m2/g). It was observed that the sulfur cathodes with KB-600, Printex XE-2, or Cabot BP-2000, which showed very similar discharge capacities one another at a low rate of 0.2 C, exhibited significantly different electrochemical behavior (the discharge capacity and midvoltage) at a high rate of 1.0 C. In particular, the sulfur cathode with KB-600 showed an extremely high capacity (831 mA h/g) with a midvoltage of 2.07 V at a 1.0 C rate, and excellent capacity retention (79%) after 50 cycles.

Gadolinium complex of DO3A-benzothiazole aniline (BTA) conjugate as a theranostic agent.

A gadolinium complex of 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DO3A) and benzothiazole-aniline (BTA) of the type [Gd(DO3A-BTA)(H2O)] has been prepared for use as a single molecule theranostic agent. The kinetic inertness and r1 relaxivity (= 3.84 mM(-1) s(-1)) of the complex compare well with those of structurally analogous Gd-DOTA. The same complex is not only tumor-specific but also intracellular, enhancing MR images of cytosols and nuclei of tumor cells such as MCF-7, MDA-MB-231, and SK-HEP-1. Both DO3A-BTA and Gd(DO3A-BTA) reveal antiproliferative activities as demonstrated by GI50 and TGI values obtainable from the cell counting kit-8 (CCK-8) assays performed on these cell lines. Ex vivo and in vivo monitoring of tumor sizes provide parallel and supportive observations for such antiproliferative activities.