Feasibility study for a fully decentralized clinical trial in participants with functional constipation symptoms.

Decentralized clinical trials (DCTs) leverage digital technologies to reduce dependency on study sites and intermediaries. DCT should be balanced with accessibility and data reliability while meeting regulatory requirements. Here, we conducted a pilot study for functional constipation symptoms to investigate the feasibility of DCT. The study was an open, fully remote, randomized clinical trial in participants who had functional constipation symptoms. Electronic consent was obtained remotely, and study volunteers were screened through web-based questionnaires. Subjects were randomized to either receive Lactobacillus and vitamin C supplements or vitamin C alone in a 1:1 ratio, which were delivered directly to subjects. Subjects kept track of bowel diaries daily during the 1-week baseline and 2-week treatment period using mobile applications. Bowel symptoms and the validity of the records were descriptively evaluated. A total of 30 subjects were randomized and completed the study. A total of 26.7% of subjects resided outside of the metropolitan area. Two-week Lactobacillus treatments increased the number of defecations (+0.80 vs. +0.46 times per week) and decreased the defecation time (-3.94 h vs. -1.62 h) compared to the comparator group. Overall, 67.1% of bowel diary records were completed in accordance with the schedule whereas 32.9% were not. Implementation of DCTs can facilitate geographic accessibility but should be guaranteed for data reliability. Prompt detection of errors and response using objective metrics would be required.

Three months-longitudinal changes in relative telomere length, blood chemistries, and self-report questionnaires in meditation practitioners compared to novice individuals during midlife.

Aging accelerates during midlife. Researches have shown the health benefits of mind-body intervention (MBI). However, whether MBI is involved with aging process has not been well understood. In this study, we approach to examine the relations of MBI with this process by investigating an aging marker of the peripheral blood, blood chemistry, and self-report questionnaires. A quasi-experimental design was applied. Experienced MBI practitioners participated in a 3-month intensive meditation training, while the age, gender-matched MBI-naïve controls led a normal daily life. Measurements were taken at before and after the 3 months for relative telomere length (RTL), blood chemistry, and self-report questionnaires including items about sleep quality, somatic symptoms, depression, anxiety, stress, emotional intelligence (EI), and self-regulation. For RTL, the repeated measures analysis of variance showed a significant group*time interaction (P = .013) with a significant post hoc result (P = .030) within the control group: RTL was significantly reduced in the control while it was maintained in the meditation group. In repeated measures analysis of variance for blood chemistries, there were significant group differences between the groups in glucose and total protein. In the post hoc comparison analysis, at post measurements, the meditation group exhibited significantly lower values than the control group in both glucose and total protein. There were significant group-wise differences in the correlations of RTL with triglyceride (TG), high-density lipoprotein (HDL), glutamic oxaloacetic transaminase and glutamic pyruvic transaminase. Any of self-report results did not show significant changes in group*time interaction. However, there were group differences with significant (P < .05) or a tendency (.05 < P < .1) level. There were significant improvements in depression, stress and EI as well as tendencies of improvement in sleep quality and anxiety, in the meditation group compared to the control group. Our results suggest that meditation practice may have a potential to modify aging process in molecular cellular level combined with changes in psychological dimension.

Pet Insects May Improve Physical Performance and Sleep in Community-Dwelling Frail Elderly People with Chronic Diseases: A Single-Arm Interventional Pilot Study.

Purpose: Animal-assisted intervention (AAI) is an effective intervention that improves the mental and physical health. However, few have examined the efficacy of pet insects as a form of AAI for prefrail and frail elderly. This study aimed to ascertain the effects of pet insects on physical performance and psychological health in community-dwelling frail elderly individuals with a chronic disease. Patients and Methods: This study was an 8 week prospective single-arm interventional pilot study that enrolled prefrail and frail community-dwelling adults aged 70 years and older, all of whom had a chronic disease and attended a daycare facility. Pet insects and appropriate equipment were provided, and supporting programs were used to educate participants about how to rear the insects and how to get close to them. Pre- and post-interventional physical and psychological functions were evaluated. Results: A total of 23 subjects (mean age, 82.78 years) were enrolled in the final analysis. The timed up-and-go-test (TUG) was used to measure functional mobility, and grip strength was used as a measure of muscle strength; both showed significant changes after the 8-week intervention (Δ = -0.35±0.73 sec, P = 0.034; and Δ = 0.73±0.99 kg, P = 0.002, respectively). In addition, the insomnia severity index (ISI) and average sleep duration improved significantly (Δ = -2.91±5.64, P = -0.021; and Δ = 0.87±1.98, P = 0.047, respectively). There were no significant changes in the results of other psychometric tests. Logistic regression analysis using the forward stepwise selection method revealed that the baseline ISI score and the absence of other comorbidities were significantly associated with the probability of positive changes in both the TUG and HS tests after the intervention. Conclusion: Pet insects may be an effective and easily applicable type of AAI, which improves physical function and sleep in prefrail and frail elderly individuals.

Combination of vegetable soup and glucan demonstrates synergistic effects on macrophage-mediated immune responses.

Vegetable soup (VS), a plant-based functional food, has been used as a traditional folk medicine and is attracting attention for its ability to enhance the immune response. ß-Glucan, a well-established and effective immunomodulator, has synergistic effects when used in combination with some bioactive compounds. In the present study, we aimed to evaluate the synergistic immunomodulatory effects of the combination of VS and ß-glucan on macrophage-mediated immune responses. ß-Glucan was demonstrated to synergistically enhance the VS-stimulated immune response, including the production of interleukin-6, tumor necrosis factor-α, and nitric oxide, mainly through the mitogen-activated protein kinase pathway in macrophages. In addition, this combination has the potential for further development in functional foods with immune-enhancing activity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00888-x.

Augmented Buyang Huanwu Decoction facilitates axonal regeneration after peripheral nerve transection through the regulation of inflammatory cytokine production.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal formulation Buyang Huanwu Decoction (BYHWD) has been used to treat cardiovascular disorders including cerebral ischemia. Recent studies showed its effects on promoting axonal regeneration after nerve injury. However, compositional reformulation supplemented with herbal components that regulates inflammation may increase its efficacy for nerve repair. AIM OF THE STUDY: We prepared a new herbal decoction by adding selected herbal components to BYHWD (augmented BYHWD; ABHD) and investigated the effect of ABHD on the production of inflammatory cytokines and axonal regeneration using an animal model of nerve transection and coaptation (NTC). MATERIALS AND METHODS: A rat model of NTC was performed on the sciatic nerve. The sciatic nerve and dorsal root ganglion (DRG) were isolated and used for immunofluorescence staining and western blot analysis. DRG tissue was also used to prepare primary neuron culture and the length of neurites was analyzed. Sensorimotor nerve activities were assessed by rotarod and von Frey tests. RESULTS: Three herbal components that facilitated neurite outgrowth were chosen to formulate ABHD. ABHD administration into the sciatic nerve 1 week or 3 months after NTC facilitated axonal regeneration. Cell division cycle 2 (Cdc2) and brain-derived neurotrophic factor (BDNF) proteins were induced from the reconnected distal portion of the sciatic nerve and the levels were further elevated by in vivo administration of ABHD. Phospho-Erk1/2 level was increased by ABHD treatment as well, implying its role in mediating retrograde transport of BDNF signals into the neuronal cell body. Production of inflammatory cytokines IL-1ß and TNF-α was induced in the reconnected nerve but attenuated by ABHD treatment. Behavioral tests revealed that ABHD treatment improved functional recovery of sensorimotor activities. CONCLUSIONS: A newly formulated ABHD is effective at regulating the production of inflammatory cytokines and promoting axonal regeneration after nerve transection and may be considered to develop therapeutic strategies for peripheral nerve injury disorders.

New 8-C-p-Hydroxylbenzylflavonol Glycosides from Pumpkin (Cucurbita moschata Duch.) Tendril and Their Osteoclast Differentiation Inhibitory Activities.

Six new 8-C-p-hydroxybenzylflavonol glycosides were isolated from a hot water extract of pumpkin (Cucurbita moschata Duch.) tendril and elucidated as 8-C-p-hydroxybenzylquercetin 3-O-rutinoside, 8-C-p-hydroxybenzoylquercetin 3-O-ß-D-glucopyranoside, 8-C-p-hydroxybenzylkaempferol 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside, 8-C-p-hydroxybenzoylkaempferol 3-O-rutinoside, 8-C-p-hydroxybenzylisorhamnetin 3-O-rutinoside, and 8-C-p-hydroxybenzylisorhamnetin 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside. Their chemical structures were determined using nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometer (ESIMS) analyses. The 8-C-p-hydroxybenzylflavonol glycosides were found to inhibit the receptor activator of nuclear factor-κB (RANKL)-induced osteoclast differentiation of bone marrow derived macrophage (BMDM), an osteoclast progenitor. Additionally, 8-C-p-hydroxybenzylflavonol glycosides effectively reduced the expression of osteoclast-related genes, such as tartrate-resistant acid phosphatase, cathepsin K, nuclear factor activated T-cell cytoplasmic 1, and dendritic cell specific transmembrane protein in RANKL-treated BMDMs. These results indicate that the 8-C-p-hydroxybenzylflavonol glycosides may be the main components responsible for the osteoclast differentiation inhibitory effect of pumpkin tendril.

Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells.

Inflammation is the root cause of many diseases that pose a serious threat to human health. Excessive inflammation can also result in preterm birth or miscarriage in pregnant women. Pumpkin (Cucurbita moschata Duchesne, CMD) is a well-known traditional health food and medicinal herb used in many countries to treat diabetes, obesity, osteoporosis, cancer and other diseases. In this study, we investigated the effects of hot water extract derived from the tendrils of C. moschata Duchesne (TCMD) on NLRP3 inflammasome activation in murine macrophages and human trophoblast cells. The TCMD treatment of LPS-primed bone marrow-derived macrophages (BMDMs) and human trophoblast cells attenuated NLRP3 inflammasome activation induced by inflammasome activators such as ATP, nigericin, and monosodium urate (MSU). TCMD treatment suppressed IL-1ß secretion in a dose-dependent manner, without affecting IL-6 secretion. In addition, TCMD inhibited NLRP3-dependent pyroptosis in BMDMs. TCMD also suppressed the release of mature IL-1ß and activation of cleaved-caspase-1 via limited ASC oligomerization. Furthermore, TCMD significantly inhibited IL-1ß secretion and pyroptotic cell death in human trophoblast cells. These results suggest that TCMD exhibits anti-inflammatory effects mediated via inhibition of NLRP3 inflammasome activation suggesting therapeutic potential against inflammatory diseases, preterm birth, and miscarriage.

High-Level Production of Bacteriotoxic Phospholipase A1 in Bacterial Host Pseudomonas fluorescens Via ABC Transporter-Mediated Secretion and Inducible Expression.

: Bacterial phospholipase A1 (PLA1) is used in various industrial fields because it can catalyze the hydrolysis, esterification, and transesterification of phospholipids to their functional derivatives. It also has a role in the degumming process of crude plant oils. However, bacterial expression of the foreign PLA1-encoding gene was generally hampered because intracellularly expressed PLA1 is inherently toxic and damages the phospholipid membrane. In this study, we report that secretion-based production of recombinant PlaA, a bacterial PLA1 gene, or co-expression of PlaS, an accessory gene, minimizes this harmful effect. We were able to achieve high-level PlaA production via secretion-based protein production. Here, TliD/TliE/TliF, an ABC transporter complex of Pseudomonas fluorescens SIK-W1, was used to secrete recombinant proteins to the extracellular medium. In order to control the protein expression with induction, a new strain of P. fluorescens, which had the lac operon repressor gene lacI, was constructed and named ZYAI strain. The bacteriotoxic PlaA protein was successfully produced in a bacterial host, with help from ABC transporter-mediated secretion, induction-controlled protein expression, and fermentation. The final protein product is capable of degumming oil efficiently, signifying its application potential.

Effects of Pet Insects on Cognitive Function among the Elderly: An fMRI Study.

Animal-assisted therapy has positive effects on cognitive function, depression, performance ability, and social functioning in elderly patients. The aim of this study was to evaluate the effects of rearing pet insects on the cognitive function of healthy elderly participants, with fMRI (functional magnetic resonance imaging) being used for this purpose. Community-dwelling right-handed elderly women (≥60 years) with normal cognitive function were enrolled and randomized at a 1:1 ratio into two groups: insect-rearing and control (n = 16) groups, with the insect-rearing group being further classified into two groups for analysis according to the subjects' scores in the Wisconsin Card Sorting Test, WCST) at the baseline fMRI: Insect-rearing group I with a relatively high score (n = 13), and insect-rearing group II with a relatively low score (n = 6). The insect-rearing groups received and reared crickets as pet insects for 8 weeks. The WCST consisted of two variations, a high level baseline (HLB) and semi-WCST version. There was a significant difference accuracy of the HLB-semi-WCST (p < 0.05) in insect-rearing group II after 8 weeks from the baseline test. In the fMRI analysis involving the WCST reaction test, increased activation was observed in the right dorsal lateral prefrontal cortex and parietal cortex in insect-rearing group II when the semi-WCST, rather than the HLB, was performed. Rearing pet insects showed positive effects on executive functions and performance improvement in elderly women. Further larger studies on the effects of pet insects on cognitive function are warranted.

Tyrosinase Inhibition Antioxidant Effect and Cytotoxicity Studies of the Extracts of Cudrania tricuspidata Fruit Standardized in Chlorogenic Acid.

In the present study, various extracts of C. tricuspidata fruit were prepared with varying ethanol contents and evaluated for their biomarker and biological properties. The 80% ethanolic extract showed the best tyrosinase inhibitory activity, while the 100% ethanolic extract showed the best total phenolics and flavonoids contents. The HPLC method was applied to analyze the chlorogenic acid in C. tricuspidata fruit extracts. The results suggest that the observed antioxidant and tyrosinase inhibitory activity of C. tricuspidata fruit extract could partially be attributed to the presence of marker compounds in the extract. In this study, we present an analytical method for standardization and optimization of C. tricuspidata fruit preparations. Further investigations are warranted to confirm the in vivo pharmacological activity of C. tricuspidata fruit extract and its active constituents and assess the safe use of the plant for the potential development of the extract as a skin depigmentation agent.

Increased microalgae growth and nutrient removal using balanced N:P ratio in wastewater.

Microalgal cultivation using wastewater is now regarded as essential for biodiesel production, as two goals can be achieved simultaneously; that is, nutrient removal efficiency and biomass production. Therefore, this study examined the effects of carbon sources, the N:P ratio, and the hydraulic retention time (HRT) to identify the optimal conditions for nutrient removal efficiency and biomass production. The effluent from a 2nd lagoon was used to cultivate microalgae. Whereas the algal species diversity and lipid content increased with a longer HRT, the algal biomass productivity decreased. Different carbon sources also affected the algal species composition. Diatoms were dominant with an increased pH when bicarbonate was supplied. However, 2% CO(2) gas led to a lower pH and the dominance of filamentous green algae with a much lower biomass productivity. Among the experiments, the highest chlorophyll-a concentration and lipid productivity were obtained with the addition of phosphate up to 0.5 mg/l P, since phosphorus was in short supply compared with nitrogen. The N and P removal efficiencies were also higher with a balanced N:P ratio, based on the addition of phosphate. Thus, optimizing the N:P ratio for the dominant algae could be critical in attaining higher algal growth, lipid productivity, and nutrient removal efficiency.

Determination of chlorfenapyr in leek grown under greenhouse conditions with GC-µECD and confirmation by mass spectrometry.

A simple analytical method was developed for the determination of chlorfenapyr residues in leeks grown under greenhouse conditions. Residues were extracted by salting out, analyzed by gas chromatography with microelectron-capture detection, and confirmed via gas chromatography-mass spectrometry. The calibration curves were found to be linear with correlation coefficients (r(2) ) in excess of 0.998. The limits of detection and quantification were 0.0015 and 0.005 mg kg(-1) , respectively. For validation purposes, recovery studies were carried out at low and high levels. Yield recovery rates were 87.27-89.64% with a relative standard deviation <6%. A maximum of 0.32 mg kg(-1) of chlorfenapyr residue was detected in leek sample sprayed three times at 7 day intervals until 7 days prior to harvest. The results of this study suggest that chlorfenapyr is acceptable for application in/on leeks under the recommended dosage regimen.

Antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in rats fed a high fat diet.

BACKGROUND: Nelumbo nucifera, known as sacred lotus, is a well-known medicinal plant and this lotus root is commonly used as food compared to different parts of this plant. This study was conducted to investigate the antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in high fat diet-induced obese rats. METHODS: Thirty-two male Sprague-Dawley rats (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus root hot water extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT group). Lotus root hot water extract was orally administrated (400 mg/kg/day) to HFR and HFRT groups and the same amount of distilled water was orally administered to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). RESULTS: The activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups compared to HF group. Thiobarbituric acid reactive substance contents in all groups fed a high fat diet were higher compared to N group. The activities of hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF group. CONCLUSIONS: These results suggest that lotus root hot water extract with taurine supplementation shows antioxidant and hepatic protective effects in high fat diet-induced obese rats.

Antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in rats fed a high fat diet.

BACKGROUND: Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The purpose of this study was to investigate the antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in high fat diet-induced obese rats. METHODS: Four week-old male Sprague-Dawley rats were randomly divided into four groups with 8 rats in each group for a period of 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf hot water extract, HFL group; high fat diet + lotus leaf hot water extract + taurine, HFLT group). Lotus leaf hot water extract was orally administrated to HFL and HFLT groups and the same amount of distilled water was orally administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). RESULTS: The body weight gain and relative weights of epididymal and retroperitoneal adipose tissues were significantly lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed lower concentrations of total cholesterol, triglyceride and low density lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT group showed better blood lipid profiles compared to HFL group. CONCLUSIONS: Lotus leaf hot water extract with taurine supplementation showed antiobesity and hypolipidemic effects in high fat diet-induced obese rats, which was more effective than lotus leaf hot water extract alone.

Neuroprotective effects of an herbal medicine, Yi-Gan San on MPP+/MPTP-induced cytotoxicity in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: A traditional herb, Yi-Gan San, has been widely used for the management of neurodegenerative disorders in traditional East Asian Medicine. AIM OF THE STUDY: The present study investigated the neuroprotective effects of Yi-Gan San in 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cytotoxicity in vitro and in vivo and sought to clarify its underlying mechanisms. MATERIALS AND METHODS: The effect of Yi-Gan San on 1-methyl-4-phenylpyridine was measured in terms of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays, caspase-3 activity, and western blot analysis of phosphorylated Akt, one of the survival-related signaling proteins in SH-SY5Y cells. The effects of Yi-Gan San were also confirmed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian mouse model using a rotarod test and tyrosine hydroxylase-immunohistochemistry. RESULTS: Pretreatment of Yi-Gan San with 1-methyl-4-phenylpyridine showed a significant protective effect on SH-SY5Y cells and significantly decreased the level of caspase-3 activity compared to the values for the 1-methyl-4-phenylpyridine-treated cells. This process increased the protein expressions of phosphorylated Akt, and an inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt, LY294002, significantly decreased this protective effect of Yi-Gan San. In the mouse Parkinson's disease model, treatment with Yi-Gan San also significantly improved motor functioning and prevented dopaminergic loss related to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine challenge. CONCLUSION: Using both in vitro and in vivo methods, this study revealed that Yi-Gan San has neuroprotective effects and rescues dopaminergic neurons from 1-methyl-4-phenylpyridine/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity, possibly via the PI3K/Akt pathway.

Fast biodiesel production with one-phase reaction.

The feasibility of fatty acid methyl ester (FAME) as a co-solvent used to increase the mass transfer between oil and methanol was investigated. FAME, as the co-solvent, does not require additional separation after the reaction because it is the end product of the reaction. To examine intermediate phenomena during the transesterification of soybean oil, the agitation speed was controlled at a slow rate. When the molar ratio of oil to methanol was 1:6 at 0.8 wt.% of KOH to oil, oil was at the bottom layer, and methanol and the catalyst were at the top layer. Under the slow agitation process, the contact surface became initially darkened with the production of FAME and glycerol. After a few minutes, the entire top layer became dark. The top layer, containing methanol, KOH, FAME, and glycerol, fell to the bottom layer and then formed the one-phase system. When 0, 5, and 10 wt.% of FAME to oil was initially introduced to the reaction mixture, the FAME content rapidly increased with the FAME concentration level. After forming the one-phase system, the rate of increase of the FAME content was very slow. The time required for the formation of the one-phase system decreased with the amount of FAME and KOH and with temperature.

Production and characterization of biodiesel from tung oil.

The feasibility of biodiesel production from tung oil was investigated. The esterification reaction of the free fatty acids of tung oil was performed using Amberlyst-15. Optimal molar ratio of methanol to oil was determined to be 7.5:1, and Amberlyst-15 was 20.8 wt% of oil by response surface methodology. Under these reaction conditions, the acid value of tung oil was reduced to 0.72 mg KOH/g. In the range of the molar equivalents of methanol to oil under 5, the esterification was strongly affected by the amount of methanol but not the catalyst. When the molar ratio of methanol to oil was 4.1:1 and Amberlyst-15 was 29.8 wt% of the oil, the acid value decreased to 0.85 mg KOH/g. After the transesterification reaction of pretreated tung oil, the purity of tung biodiesel was 90.2 wt%. The high viscosity of crude tung oil decreased to 9.8mm(2)/s at 40 degrees C. Because of the presence of eleostearic acid, which is a main component of tung oil, the oxidation stability as determined by the Rancimat method was very low, 0.5h, but the cold filter plugging point, -11 degrees C, was good. The distillation process did not improve the fatty acid methyl ester content and the viscosity.

Blending effects of biodiesels on oxidation stability and low temperature flow properties.

To improve the oxidation stability and the low temperature flow properties of a biodiesel mixture, the dependence of the oxidation stability and the cold filter plugging point (CFPP) on the fatty acid compositions was examined. Three different kinds of biodiesels, palm, rapeseed, and soybean biodiesels, were blended with the different weight ratios. The oxidation stability and the CFPP of the blended biodiesels had a close relationship with the compositions of the major fatty acid components. The oxidation stability of the blended biodiesels decreased as the total contents of the linoleic and linolenic acids increased. The correlation was obtained as Y=117.9295/X+2.5905 (0