Efficacy of Blue LED Phototherapy on Sleep Quality and Behavioral and Psychological Symptoms of Dementia: A Double-Blind Randomized Controlled Trial.

INTRODUCTION: People with dementia often experience behavioral and psychological symptoms of dementia (BPSD), which are a major cause of caregiver burden and institutionalization. Therefore, we conducted a double-blind, parallel-group randomized controlled trial to examine the efficacy of blue-enriched light therapy for BPSD in institutionalized older adults with dementia. METHODS: Participants were enrolled and randomly allocated into blue-enriched light therapy (N = 30) or the conventional light group (N = 30) for 60 min in 10 weeks with five sessions per week. The primary outcome was sleep quality measured by actigraphy and Pittsburgh Sleep Quality Index (PSQI). The secondary outcome was overall BPSD severity (Cohen-Mansfield Agitation Inventory [CMAI] and Neuropsychiatric Inventory [NPI-NH]). The outcome indicators were assessed at baseline, mid-test, immediate posttest, 1-month, 3-month, and 6-month follow-up. The effects of the blue-enriched light therapy were examined by the generalized estimating equation model. RESULTS: Blue-enriched light therapy revealed significant differences in the objective sleep parameters (sleep efficiency: ß = 5.81, Waldχ2 = 32.60, CI: 3.82; 7.80; sleep latency: ß = -19.82, Waldχ2 = 38.38, CI:-26.09; -13.55), subjective sleep quality (PSQI: ß = -2.07, Waldχ2 = 45.94, CI: -2.66; -1.47), and overall BPSD severity (CMAI: ß = -0.90, Waldχ2 = 14.38, CI: -1.37; -0.44) (NPI-NH: ß = -1.67, Waldχ2 = 30.61, CI: -2.26; -1.08) compared to conventional phototherapy immediate posttest, 1-month, 3-month, and 6-month follow-up. Furthermore, the effects for sleep efficiency and sleep latency lasted for up to 6 months. In the subscale analysis, the differences of the behavioral symptoms changed significantly between the groups in physical/nonaggressive (CI: -1.01; -0.26) and verbal/nonaggressive (CI: -0.97; -0.29). CONCLUSIONS: Blue-enriched light therapy is a feasible low-cost intervention that could be integrated as a comprehensive therapy program for BPSD among older adults with dementia.

Suspected-target and non-targeted screenings of phosphodiesterase 5 inhibitors in herbal remedies using liquid chromatography-quadrupole time-of-flight-mass spectrometry.

The lucrative market of herbal remedies spurs rampant adulteration, particularly with pharmaceutical drugs and their unapproved analogues. A comprehensive screening strategy is, therefore, warranted to detect these adulterants and, accordingly, to safeguard public health. This study uses the data-dependent acquisition of liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS) to screen phosphodiesterase 5 (PDE5) inhibitors in herbal remedies using suspected-target and non-targeted strategies. For the suspected-target screening, we used a library comprising 95 PDE5 inhibitors. For the non-targeted screening, we adopted top-down and bottom-up approaches to flag novel PDE5 inhibitor analogues based on common fragmentation patterns. LC-QTOF-MS was optimised and validated for capsule and tablet dosage forms using 23 target analytes, selected to represent different groups of PDE5 inhibitors. The method exhibited excellent specificity and linearity with limit of detection and limit of quantification of <40 and 80 ng/mL, respectively. The accuracy ranged from 79.0% to 124.7% with a precision of <14.9% relative standard deviation. The modified, quick, easy, cheap, effective, rugged, and safe extraction provided insignificant matrix effect within -9.1%-8.0% and satisfactory extraction recovery of 71.5%-105.8%. These strategies were used to screen 52 herbal remedy samples that claimed to enhance male sexual performance. The suspected-target screening resulted in 33 positive samples, revealing 10 target analytes and 2 suspected analytes. Systematic MS and tandem MS interrogations using the non-targeted screening returned insignificant signals, indicating the absence of potentially novel analogues. The target analytes were quantified from 0.03 to 121.31 mg per dose of each sample. The proposed strategies ensure that all PDE5 inhibitors are comprehensively screened, providing a useful tool to curb the widespread adulteration of herbal remedies.

Green tea polyphenols ameliorate metabolic abnormalities and insulin resistance by enhancing insulin signalling in skeletal muscle of Zucker fatty rats.

In the present study, we evaluated the metabolic effects of green tea polyphenols (GTPs) in high-fat diet (HFD) fed Zucker fatty (ZF) rats, in particular the effects of GTP on skeletal muscle insulin sensitivity. Body weight, visceral fat, glucose tolerance, lipid profiles and whole-body insulin sensitivity were measured in HFD-fed ZF rats after 8-week-treatment with GTP (200 mg/kg of body weight) or saline (5 ml/kg of body weight). Zucker lean rats were studied as controls. Ex vivo insulin-mediated muscle glucose uptake was assessed. Immunoblotting was used to evaluate the expression of key insulin signalling proteins in skeletal muscle. GTP treatment attenuated weight gain (P<0.05) and visceral fat accumulation (27.6%, P<0.05), and significantly reduced fasting serum glucose (P<0.05) and insulin (P<0.01) levels. Homoeostasis model assessment of insulin resistance (HOMA-IR), a measure of insulin resistance, was lower (P<0.01) in GTP-treated animals compared with ZF controls. Moreover, insulin-stimulated glucose uptake by isolated soleus muscle was increased (P<0.05) in GTP-ZF rats compared with ZF-controls. GTP treatment attenuated the accumulation of ectopic lipids (triacyl- and diacyl-glycerols), enhanced the expression and translocation of glucose transporter-4, and decreased pSer612IRS-1 and increased pSer473Akt2 expression in skeletal muscle. These molecular changes were also associated with significantly decreased activation of the inhibitory (muscle-specific) protein kinase (PKC) isoform, PKC-θ. Taken together, the present study has shown that regular ingestion of GTP exerts a number of favourable metabolic and molecular effects in an established animal model of obesity and insulin resistance. The benefits of GTP are mediated in part by inhibiting PKC-θ and improving muscle insulin sensitivity.

The effectiveness of eye movement desensitization and reprocessing toward anxiety disorder: A meta-analysis of randomized controlled trials.

BACKGROUND: Eye Movement Desensitization and Reprocessing (EMDR) has been well established as an effective treatment for post-traumatic stress disorder (PTSD). However, PTSD has been re-categorized as part of trauma and stressor-related disorders instead of anxiety disorders. We conducted the first meta-analysis on Randomized Controlled Trials to evaluate the effectiveness of EMDR on reducing symptoms of anxiety disorders. METHODS: A manual and systematic search using various databases and reference lists of systematic review articles published up to December 2018 was conducted. The symptoms of anxiety, phobia, panic, traumatic feelings and behaviors/somatic symptoms were examined. Hedges' g effect sizes were computed, and random effect models were used for all analyses. RESULTS: A total of 17 trials with 647 participants were included in this meta-analysis. EMDR was associated with a significant reduction of anxiety (g = -0.71; 95% CI: -0.96 to -0.47), panic (g = -0.62; 95% CI: -1.10 to -0.14), phobia (g = -0.45; 95% CI: -0.81 to -0.08), behavioural/somatic symptoms (g = -0.40; 95% CI: -0.63 to -0.12), but not traumatic feelings (g = -0.48; 95% CI: -1.14 to -0.18). Subgroup analysis revealed greater effects of EMDR if compared to passive control. However, the effects were not significantly different based on the duration, number of therapy sessions, or the number of weekly sessions. CONCLUSIONS: Our meta-analysis indicates that EMDR is efficacious for reducing symptoms of anxiety, panic, phobia, and behavioural/somatic symptoms. Further research is needed to explore EMDR's long term efficacy on anxiety disorders.

Determination of phosphodiesterase 5 (PDE5) inhibitors in instant coffee premixes using liquid chromatography-high-resolution mass spectrometry (LC-HRMS).

As a widely consumed beverage, coffee tends to be a target for intentional adulteration. This study describes the application of modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) coupled to liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for simultaneous screening, identification, and quantification of undeclared phosphodiesterase 5 (PDE5) inhibitors in instant coffee premixes (ICPs). The mass spectrometer was operated in auto MS/MS acquisition for simultaneous MS and MS/MS experiments. Qualitative establishments from the suspected-target screening and targeted identification processes led to an unambiguous analyte assignment from the protonated molecule ([M+H]+) precursor ion which is subsequently used for quantification of 23 targeted PDE5 inhibitors. The analytical method validation covered specificity, linearity, range, accuracy, limit of detection (LOD), limit of quantification (LOQ), precisions, matrix effect (ME), and extraction recovery (RE). The specificity was established using the optimised chromatographic separation as well as the distinguishable [M+H]+ precursor ion. The linearity of each target analyte was demonstrated with a coefficient of determination (r2) of >0.9960 over the expected range of sample concentrations. The accuracy ranged from 88.1%-119.3% with LOD and LOQ of <70 ng/mL and 80 ng/mL, respectively. Excellent precisions were established within 0.4%-9.1% of the relative standard deviation. An insignificant ME within -5.2% to +8.7% was achieved using three different strategies of chromatography, sample extraction, and sample dilution. The RE was good for all target analytes within 84.7%-123.5% except for N-desethylacetildenafil at low (53.8%) and medium (65.1%) quality control levels. The method was successfully applied to 25 samples of ICPs where 17 of them were found to be adulterated with PDE5 inhibitors and their analogues. Further quantification revealed the total amount of these adulterants ranged from 2.77 to 121.64 mg per sachet.

Green tea polyphenols ameliorate non-alcoholic fatty liver disease through upregulating AMPK activation in high fat fed Zucker fatty rats.

AIM: To investigate protective effects and molecular mechanisms of green tea polyphenols (GTP) on non-alcoholic fatty liver disease (NAFLD) in Zucker fatty (ZF) rats. METHODS: Male ZF rats were fed a high-fat diet (HFD) for 2 wk then treated with GTP (200 mg/kg) or saline (5 mL/kg) for 8 wk, with Zucker lean rat as their control. At the end of experiment, serum and liver tissue were collected for measurement of metabolic parameters, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), inflammatory cytokines and hepatic triglyceride and liver histology. Immunoblotting was used to detect phosphorylation of AMP-activated protein kinase (AMPK) acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein 1c (SREBP1c). RESULTS: Genetically obese ZF rats on a HFD presented with metabolic features of hepatic pathological changes comparable to human with NAFLD. GTP intervention decreased weight gain (10.1%, P = 0.052) and significantly lowered visceral fat (31.0%, P < 0.01). Compared with ZF-controls, GTP treatment significantly reduced fasting serum insulin, glucose and lipids levels. Reduction in serum ALT and AST levels (both P < 0.01) were observed in GTP-treated ZF rats. GTP treatment also attenuated the elevated TNFα and IL-6 in the circulation. The increased hepatic TG accumulation and cytoplasmic lipid droplet were attenuated by GTP treatment, associated with significantly increased expression of AMPK-Thr172 (P < 0.05) and phosphorylated ACC and SREBP1c (both P < 0.05), indicating diminished hepatic lipogenesis and triglycerides out flux from liver in GTP treated rats. CONCLUSION: The protective effects of GTP against HFD-induced NAFLD in genetically obese ZF rats are positively correlated to reduction in hepatic lipogenesis through upregulating the AMPK pathway.

Characterisation of Bone Beneficial Components from Australian Wallaby Bone.

Background: Osteoporosis is a condition in which the bones become brittle, increasing the risk of fractures. Complementary medicines have traditionally used animal bones for managing bone disorders, such as osteoporosis. This study aimed to discover new natural products for these types of conditions by determining mineral and protein content of bone extracts derived from the Australian wallaby. Methods: Inductively coupled plasma-mass spectrometry and Fourier transform infrared spectroscopic analysis were used for mineral tests, proteome analysis was using LC/MS/MS and the effects of wallaby bone extracts (WBE)s on calcium deposition and alkaline phosphatase activity were evaluated in osteogenic cells derived from adipose tissue-derived stem cells (ADSCs). Results: Concentrations of calcium and phosphorus were 26.21% and 14.72% in WBE respectively. Additionally, minerals found were wide in variety and high in concentration, while heavy metal concentrations of aluminium, iron, zinc and other elements were at safe levels for human consumption. Proteome analysis showed that extracts contained high amounts of bone remodelling proteins, such as osteomodulin, osteopontin and osteoglycin. Furthermore, in vitro evaluation of WBEs showed increased deposition of calcium in osteoblasts with enhanced alkaline phosphatase activity in differentiated adipose-derived stem cells. Conclusion: Our results demonstrate that wallaby bone extracts possess proteins and minerals beneficial for bone metabolism. WBEs may therefore be used for developing natural products for conditions such as osteoporosis and further investigation to understand biomolecular mechanism by which WBEs prevent osteoporosis is warranted.

Comparison of Cytotoxicity and the Anti-Adipogenic Effect of Green Tea Polyphenols with Epigallocatechin-3-Gallate in 3T3-L1 Preadipocytes.

Recent studies have demonstrated the effects of green tea polyphenols (GTP) and epigallocatechin-3-gallate (EGCG) on obesity. However, high doses of EGCG have also exhibited cytotoxicity. The aim of this study was to compare total GTP with purified EGCG on cytotoxicity, and to investigate the effects and the molecular mechanism of total GTP and EGCG on adipogenesis. Cytotoxicity was determined by cell viability assay. For the adipogenesis study, 3T3-L1 preadipocytes were incubated with three doses of GTP (1, 10, and 100 µg/ml) and the effect of EGCG (6.8 µg/ml) was compared with 10 µg/ml GTP containing 68% EGCG. Oil Red O staining and triglyceride content assay were carried out 10 days after differentiation and treatment. Adipogenic regulators CCAAT element binding protein α (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein-1c (SREBP-1c) were determined by qRT-PCR and immunoblotting. GTP at 1000 µg/ml and EGCG (68 and 680 µg/ml) significantly affected cell viability. Purified EGCG had greater cytotoxicity than corresponding doses of GTP. About 10 µg/ml of GTP showed stronger reduction in triglyceride accumulation than EGCG treatment. Transcriptional factors of C/EBPα, SREBP-1c and PPARγ were markedly decreased in both GTP and EGCG-treated cells and GTP exhibited stronger inhibitory effects on C/EBPα and PPARγ protein expression than EGCG (p < 0.05). In conclusion, total GTP exerted greater inhibitory effects than purified EGCG on adipogenesis through down-regulating the adipogenic factor C/EBPα, SREBP-1c and PPARγ expression. These findings support that a polyphenol mixture is safer and more effective than EGCG alone for preventing obesity and obesity-related chronic diseases.

Green tea polyphenol epigallocatechin-3-gallate enhance glycogen synthesis and inhibit lipogenesis in hepatocytes.

The beneficial effects of green tea polyphenols (GTP) against metabolic syndrome and type 2 diabetes by suppressing appetite and nutrient absorption have been well reported. However the direct effects and mechanisms of GTP on glucose and lipid metabolism remain to be elucidated. Since the liver is an important organ involved in glucose and lipid metabolism, we examined the effects and mechanisms of GTP on glycogen synthesis and lipogenesis in HepG2 cells. Concentrations of GTP containing 68% naturally occurring (-)-epigallocatechin-3-gallate (EGCG) were incubated in HepG2 cells with high glucose (30 mM) under 100 nM of insulin stimulation for 24 h. GTP enhanced glycogen synthesis in a dose-dependent manner. 10 µM of EGCG significantly increased glycogen synthesis by 2fold (P < 0.05) compared with insulin alone. Western blotting revealed that phosphorylation of Ser9 glycogen synthase kinase 3 ß and Ser641 glycogen synthase was significantly increased in GTP-treated HepG2 cells compared with nontreated cells. 10 µM of EGCG also significantly inhibited lipogenesis (P < 0.01). We further demonstrated that this mechanism involves enhanced expression of phosphorylated AMP-activated protein kinase α and acetyl-CoA carboxylase in HepG2 cells. Our results showed that GTP is capable of enhancing insulin-mediated glucose and lipid metabolism by regulating enzymes involved in glycogen synthesis and lipogenesis.

Managing the combination of nonalcoholic Fatty liver disease and metabolic syndrome with chinese herbal extracts in high-fat-diet fed rats.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS). The aim of the study was to evaluate the effects of Chinese herbal extracts from Salvia miltiorrhiza and Gardenia jasminoides (SGE) on the combination of NAFLD and MetS induced by a high-fat diet (HFD) in rats. After 6 weeks of HFD feeding, rats (n = 10 each group) were treated with saline, rosiglitazone (RSG), and SGE for 4 weeks. HFD rats were obese, hyperinsulinemic, hyperlipidemic and increased hepatic enzymes with the histological images of NAFLD. Treatment with SGE significantly reduced serum triglycerides (TG), nonesterified fatty acids and enhanced insulin sensitivity, and ameliorated the elevated serum hepatic enzymes compared with HFD-saline group. SGE treatment also attenuated hepatic TG by 18.5% (P < 0.05). Histological stains showed SGE decreased lipids droplets in hepatocytes (P < 0.05) and normalized macrovesicular steatosis in HFD rats. Significant reduction of TNF- α and IL6 in adipose tissue was detected in SGE treated rats. The anti-inflammatory action may be, at least in part, the mechanism of SGE on MetS associated with NAFLD. This study discovered that SGE is capable of managing metabolic and histological abnormalities of NAFLD and MetS. SGE may be an optimal treatment for the combination of NAFLD and MetS.

In vitro investigation of anti-diabetic effect of Taxus cuspidate extracts by ultrasound assisted method.

Extracting active components from Chinese medicinal herbs efficiently is a key step in the investigation of their pharmacological effects and modes of action. In this project, we compared the ultrasound-assisted method and the conventional solvent method for extracting the active compound of Taxus cuspidate (dong bei hong dou shan). Through the analysis of various extractions with a quadruple time-of-fight (Q-TOF) LC/MS, we demonstrated that the ultrasound-assisted method reduced solvent consumption and had shorter extraction time, while the extraction yields of the active compound (taxol) were equivalent to or even higher than those obtained with the conventional solvent extraction method. Through the comparison of Taxus cuspidate extracts (TCEs) with different concentrations of acetone and ethanol, we proved that 50% ethanol was an optimal solvent for extracting taxol from Taxus cuspidate. Based on traditional Chinese medicine (TCM) literature, we further determined whether TCEs possess antidiabetic effects by testing glucose uptake in 3T3-L1 adipocytes treated with TCEs from Taxus cuspidate bark and twigs under insulin stimulation (100 nM). The results showed that neither taxol (10 µg/ml) nor TCEs (1 and 0.1 mg/ml) changed glucose uptake significantly compared with insulin alone. This study demonstrated that the ultrasound-assisted method with 50% ethanol is a highly efficient approach for extracting Taxus cuspidate, which may be applicable for extraction of other Chinese medicinal herbs. Extracts of Taxus cuspidate bark and twigs had no effect on insulin stimulated-glucose uptake in vitro. This result conflicts with the description in TCM literature. Further in vivo study to clarify Taxus cuspidate's metabolic actions is necessary.