Paeonol alleviates postmenopause-induced neuropsychiatric symptoms through the modulation of GPR30 in ovariectomized mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The Moutan cortex (MC), the root bark of Paeonia suffruticosa Anderws (Paeoniaceae), has been historically employed in traditional herbal medicine for addressing women's ailments by replenishing kidney Yin. AIM OF THE STUDY: We aimed to explore if paeonol, an active constituent of MC, could ameliorate neuropsychiatric symptoms, such as anxiety, depression, and cognitive impairments, associated with post-menopausal syndrome (PMS) in an ovariectomized (OVX) mouse model. MATERIALS AND METHODS: The experimental design comprised 6 groups, including a sham group, OVX group, paeonol administration groups (3, 10 or 30 mg/kg, p.o.), and an estradiol (E2)-treated positive control group. Behavioral tests including the open field, novel object recognition, Y-maze, elevated plus-maze, splash, and forced swimming tests were conducted. In addition, we investigated the effets of paeonol on the phosphorylated levels of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), as well as on the expression levels of G protein-coupled receptor (GPR30) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus. RESULTS: Paeonol treatment (10 and 30 mg/kg, p.o.) effectively reversed the cognitive decline in OVX mice, measured by the novel object recognition and Y-maze tests, similar to that in the positive control group. Additionally, it alleviated anxiety- and depressive-like behaviors, as evaluated by the elevated plus-maze test, splash test, and forced swimming test. Paeonol restored GPR30 expression levels in the prefrontal cortex and hippocampus, mirroring the effects of E2 administration. Furthermore, it reversed the reduced expression levels of the PI3K-Akt-mTOR signaling pathway in the prefrontal cortex and hippocampus and increased BDNF expression in the hippocampus of OVX mice. CONCLUSION: This research suggests that paeonol would be beneficial for alleviating PMS-associated cognitive impairment, anxiety and depression.

Universal selective transfer printing via micro-vacuum force.

Transfer printing of inorganic thin-film semiconductors has attracted considerable attention to realize high-performance soft electronics on unusual substrates. However, conventional transfer technologies including elastomeric transfer printing, laser-assisted transfer, and electrostatic transfer still have challenging issues such as stamp reusability, additional adhesives, and device damage. Here, a micro-vacuum assisted selective transfer is reported to assemble micro-sized inorganic semiconductors onto unconventional substrates. 20 µm-sized micro-hole arrays are formed via laser-induced etching technology on a glass substrate. The vacuum controllable module, consisting of a laser-drilled glass and hard-polydimethylsiloxane micro-channels, enables selective modulation of micro-vacuum suction force on microchip arrays. Ultrahigh adhesion switchability of 3.364 × 106, accomplished by pressure control during the micro-vacuum transfer procedure, facilitates the pick-up and release of thin-film semiconductors without additional adhesives and chip damage. Heterogeneous integration of III-V materials and silicon is demonstrated by assembling microchips with diverse shapes and sizes from different mother wafers on the same plane. Multiple selective transfers are implemented by independent pressure control of two separate vacuum channels with a high transfer yield of 98.06%. Finally, flexible micro light-emitting diodes and transistors with uniform electrical/optical properties are fabricated via micro-vacuum assisted selective transfer.

The effect of pharmacological treatment and lifestyle modification in patients with nonalcoholic fatty liver disease: An umbrella review of meta-analyses of randomized controlled trials.

Nonalcoholic fatty liver disease (NAFLD) is a liver disease that affects approximately 25% of the world's population, and various treatments have been applied for NAFLD patients. We compared the effectiveness of each intervention conducted to treat NAFLD by evaluating meta-analyses of pharmacological interventions and lifestyle modification including diet and exercise. We searched Pubmed/Medline, Embase, and Cochrane Library and included meta-analyses of randomized controlled trials investigating the effects of pharmacological intervention and lifestyle modification on NAFLD. The quality of included meta-analyses was evaluated by AMSTAR-2. If the effect size was expressed as mean difference, it was converted to standardized mean difference based on the random-effects model. A total of 1694 meta-analyses were identified, and 27 meta-analyses were eventually included in the review. Regarding pharmacological interventions, there was a high strength of evidence for the ALT reduction effect of silymarin on inactive controls (SMD = 0.88, p < 0.01, seven trials, 518 participants). Meanwhile, it was confirmed that appropriate diet and exercise were important in reducing liver fat (SMD = 1.51, p < 0.01, 12 trials, 765 participants). This umbrella review assessed the effects of pharmacological interventions and lifestyle modifications in the treatment of NAFLD. The results of this review can be utilized for clinical decisions when treating NAFLD patients.

Effects of exogenous melatonin supplementation on health outcomes: An umbrella review of meta-analyses based on randomized controlled trials.

Various melatonin supplementations have been developed to improve health outcomes in various clinical conditions. Thus, we sought to evaluate and summarize the effect of melatonin treatments in clinical settings for health outcomes. We searched PubMed/Medline, Embase, and Cochrane Library from inception to 4 February 2021. We included meta-analyses of randomized controlled trials investigating the melatonin intervention for any health outcome. Based on the different effect sizes of each meta-analysis, we calculated random models' standardized mean differences or risk ratios. We observed robust evidence supported by statistical significance with non-considerable heterogeneity between studies for sleep-related problems, cancer, surgical patients, and pregnant women. Patients with sleep disorder, sleep onset latency (SMD 0.33, 95% CI: 0.10 - 0.56, P < 0.01) were significantly improved whereas no clear evidence was shown with sleep efficiency (1.10, 95% CI: -0.26 to 2.45). The first analgesic requirement time (SMD 5.81, 95% CI: 2.57-9.05, P < 0.001) of surgical patients was distinctly improved. Female patients under artificial reproductive technologies had significant increase in the top-quality embryos (SMD 0.53, 95% CI: 0.27 - 0.79, P < 0.001), but no statistically clear evidence was found in the live birth rate (SMD 1.20, 95% CI: 0.83 - 1.72). Survival at one year (RR 1.90, 95% CI: 1.28 - 2.83, P < 0.005) significantly increased with cancer patients. Research on melatonin interventions to treat clinical symptoms and sleep problems among diverse health conditions was identified and provided considerable evidence. Future well-designed randomized clinical trials of high quality and subgroup quantitative analyses are essential.

Antithrombotic Effect of Artemisia princeps Pampanini Extracts in Vitro and in FeCl3 -Induced Thrombosis Rats.

Extracts of several plants possess antithrombotic effects. Herein, we examined the antithrombotic effects of different extracts of Artemisia princeps Pampanini prepared using distilled water, hot distilled water, 70% ethanol, or subcritical water. The antithrombotic effects were determined using a co-culture system consisting of tumor necrosis factor-alpha (TNF-α)-treated EA.hy926 cells and THP-1 cells. In addition, the coagulation time of plasma collected from healthy volunteers was evaluated in terms of the prothrombin time and activated partial thromboplastin time. A carotid arterial thrombosis model was induced by ferric chloride in Sprague Dawley rats. The rats were treated with either sterile water or three different doses of the subcritical water extract for 2 weeks. The thrombus weight, gene expression of cell adhesion molecules, and histological characteristics were assessed. The results of in vitro studies revealed a significant inhibition in the adhesion of monocytes to EA.hy926 cells stimulated by TNF-α in the subcritical water extract-treated group. We also observed considerable suppression of the occlusion and mRNA expression of cell adhesion molecules in the in vivo experiments. This study suggests that Artemisia princeps Pampanini may have the potential to improve blood coagulation.

Cinnamon subcritical water extract attenuates intestinal inflammation and enhances intestinal tight junction in a Caco-2 and RAW264.7 co-culture model.

Cinnamon is known to have several physiological effects; the effects of Cinnamomum japonicum Sieb. on anti-inflammation and tight junctions were investigated in the cellular intestinal inflammation model. Cinnamon subcritical water extract (CSWE) significantly down-regulated the protein and expression levels of nitrite, prostaglandin E2 (PGE2), interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB) activity, and the phosphorylation of the factors of the NF-κB pathway. It also significantly decreased the permeability but increased the transepithelial electrical resistance (TEER) value and the protein and expression levels of tight junction proteins (i.e., zonula occludens (ZO)-1, occludin, and claudin-1). Furthermore, cinnamic acid and cinnamaldehyde, the major components of C. japonicum, inhibited the phosphorylation of the NF-κB pathway and increased the tight junction protein expression. CSWE from C. japonicum may improve intestinal health by enhancing tight junctions and inhibiting inflammation of the intestines.

The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis.

INTRODUCTION: The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. AIM: To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. METHODS: Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. MAIN OUTCOME MEASURE: The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. RESULTS: In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. CLINICAL IMPLICATIONS: Arginine supplements can be recommended to patients with mild to moderate ED. STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. CONCLUSION: The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED. Rhim HC, Kim MS, Park Y-J, et al. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med 2019;16:223-234.

Deer Bone Extract Supplementation for Mild-to-Moderate Knee Osteoarthritis Symptoms: A Randomized, Double-Blind, Placebo-Controlled Trial.

In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy of deer bone extract (DBE) in participants with knee osteoarthritis (OA). We enrolled 50 participants aged 50-70 years, having knee OA with a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score ≥5.0. The participants were assigned to the placebo or DBE group (550 mg/day) for 12 weeks. The outcome measures were as follows: pain score on the visual analog scale (VAS); WOMAC score; and blood and urine biomarkers. In the DBE group, VAS scores, WOMAC total scores, and WOMAC subscores (for pain, stiffness, and physical function) improved significantly compared with the baseline values. However, there was no significant difference in outcomes between the DBE and placebo groups. The present findings suggest that DBE may mildly reduce joint pain and stiffness and improve joint function in patients with painful knee OA.