The effects of biogenic amines in Chinese Huangjiu on the behavior of mice and hangover headache-related indices.

Huangjiu (Chinese rice wine) is a popular and traditional alcoholic beverage in China; however, the consumption of Huangjiu readily results in hangover symptoms. The aim of this study was to identify the main components associated with behavioral inhibition, headache, and the relevant mechanisms by using a mice hangover model. The results of an open-field experiment revealed that the key biogenic amine associated with mice behavior was histamine, which inhibited the behavior activity of mice in a dose-dependent manner. Moreover, histamine treatment decreased the levels of serotonin (5-HT) and 5-hydroxyindole acetic acid. In addition, the levels of dopamine and nitric oxide, which are associated with migraine, increased in the brain tissue of mice. In addition, the expression of receptor genes of 5-HT, including Htr1a, Htr1f, and Htr2c, is essential in regulating various behaviors and mental activities. In conclusion, the present study demonstrated that histamine is a key component in Huangjiu, and it is related to hangover symptoms by affecting the level of 5-HT and its receptors.

Novel Curcumin Derivative-Decorated Ultralong-Circulating Paclitaxel Nanoparticles: A Novel Delivery System with Superior Anticancer Efficacy and Safety.

Purpose: Paclitaxel (PTX) has been widely utilized for the treatment of breast cancer. However, drawbacks, such as poor aqueous solubility, rapid blood clearance and severe toxicity, greatly reduce its efficacy and safety. Herein, a novel self-developed curcumin derivative (CUD) was chosen as the carrier to develop a long-acting PTX nano-delivery system (PTX-Sln@CUD) in order to improve its pharmacokinetic behavior, anti-breast cancer efficacy and safety. Methods: PTX-Sln@CUD was prepared using solid dispersion and ultrasonic technology. Relevant physical and chemical properties, including stability and release behavior, were characterized. The clearance of PTX-Sln@CUD in vivo was studied by pharmacokinetic experiments. The anti-tumor activity of PTX-Sln@CUD was investigated in vitro and in vivo. Hemolysis experiments, acute toxicity and cumulative toxicity studies were performed in mice to determine the safety of PTX-Sln@CUD. Results: The average particle size, PDI, Zeta potential, encapsulation efficiency and loading efficiency of the PTX-Sln@CUD were 238.5 ± 4.79 nm, 0.225 ± 0.011, -33.8 ± 1.26 mV, 94.20 ± 0.49% and 10.98 ± 0.31%, respectively. PTX-Sln@CUD was found to be stable at room temperature for half a year. The cumulative release rates of PTX-Sln@CUD at 24, 96 and 168 h were 17.98 ± 2.60, 57.09 ± 2.32 and 72.66 ± 4.16%, respectively, which were adherent to zero-order kinetics. T1/2, MRT (0-t) and AUC (0-t) of the PTX-Sln@CUD group were 4.03-fold (44.293 h), 7.78-fold (38.444 h) and 6.18-fold (14.716 mg/L*h) of the PTX group, respectively. PTX-Sln@CUD group demonstrated stronger anti-breast cancer activity than the PTX group. Importantly, the PTX-Sln@CUD group was safer compared to the PTX group both in vitro and in vivo. Conclusion: PTX-Sln@CUD was verified as promising therapeutic nanoparticles for breast cancer and provided a novel strategy to solve the problem of low efficacy and poor safety of clinical chemotherapy drugs.

Formulation of the novel structure curcumin derivative-loaded solid lipid nanoparticles: synthesis, optimization, characterization and anti-tumor activity screening in vitro.

This study investigated the effect of structural modification of Curcumin (CU) combined with the solid lipid nanoparticles (SLN) drug delivery system on anti-tumor activity in vitro. A new structure of Curcumin derivative (CU1) was successfully synthesized by modifying the phenolic hydroxyl group of CU. CU1 was two times more stable than CU at 45 °C or constant light. The SLN containing CU1 (CU1-SLN) was prepared, and the particle size, polydispersity index, entrapment efficiency, drug loading, and zeta potential of CU1-SLN were (104.1 ± 2.43) nm, 0.22 ± 0.008, (95.1 ± 0.38) %, (4.28 ± 0.02) %, and (28.3 ± 1.60) mV, respectively. X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) showed that CU1 is amorphous in SLN. CU1-SLN released the drug slowly for 48 h, while CU and CU1 were released rapidly within 8 h. In terms of cytotoxicity, CU1 exhibited a 1.5-fold higher inhibition than CU against A549 and SMMC-7721 cells, while CU1-SLN showed 2-fold higher inhibition than CU1. Both CU1 and CU1-SLN reduced the toxicity in normal hepatocytes compared with CU (2.6-fold and 12.9-fold, respectively). CU1-SLN showed a significant apoptotic effect (p < 0.05). In summary, CU1 retained the inhibitory effect of CU against tumor cells, while improving stability and safety. Additionally, CU1-SLN presents a promising strategy for the treatment of liver and lung cancer.

Patient-Derived Xenograft: A More Standard "Avatar" Model in Preclinical Studies of Gastric Cancer.

Despite advances in diagnosis and treatment, gastric cancer remains the third most common cause of cancer-related death in humans. The establishment of relevant animal models of gastric cancer is critical for further research. Due to the complexity of the tumor microenvironment and the genetic heterogeneity of gastric cancer, the commonly used preclinical animal models fail to adequately represent clinically relevant models of gastric cancer. However, patient-derived models are able to replicate as much of the original inter-tumoral and intra-tumoral heterogeneity of gastric cancer as possible, reflecting the cellular interactions of the tumor microenvironment. In addition to implanting patient tissues or primary cells into immunodeficient mouse hosts for culture, the advent of alternative hosts such as humanized mouse hosts, zebrafish hosts, and in vitro culture modalities has also facilitated the advancement of gastric cancer research. This review highlights the current status, characteristics, interfering factors, and applications of patient-derived models that have emerged as more valuable preclinical tools for studying the progression and metastasis of gastric cancer.

Anti-lung cancer effect of paclitaxel solid lipid nanoparticles delivery system with curcumin as co-loading partner in vitro and in vivo.

The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully co-encapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CU + PTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PC-SLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CU + PTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-κB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer.

The Effects of a Novel Curcumin Derivative Loaded Long-Circulating Solid Lipid Nanoparticle on the MHCC-97H Liver Cancer Cells and Pharmacokinetic Behavior.

Purpose: The objective of this study was to develop long-circulating solid lipid nanoparticles (LSLN) containing a novel curcumin (CU) derivative (CU1), to improve CU1's pharmacokinetic behavior and its anti-cancer effects in MHCC-97H liver cancer cells. Methods: LSLN loaded with CU1 (CU1-LSLN) was optimized and characterized. The cell biological properties and the anti-cancer mechanism of CU1-LSLN on MHCC-97H cells were evaluated by MTT, flow cytometry, Transwell, and Western blot. CU1-LSLN was further evaluated for pharmacokinetic behavior, biodistribution, and liver toxicity in SD rats. Results: The optimized CU1-LSLN formulation showed the ideal particle size (PS), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE%), and drug loading (DL%) of 122.10 ± 6.63 nm, 0.19 ± 0.02, -36.30 ± 1.25 mV, 94.98 ± 0.90% and 4.53 ± 0.69%, respectively. X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrometry (FTIR) indicated that CU1 was well encapsulated by LSLN and existed in amorphous form. Storage stability of CU1-LSLN was up to 180 days with a sustained-release of drug over 96 h. The uptake efficiency of CU1-LSLN to MHCC-97H cells was 3.24 and 2.98 times higher than that of CU and CU1 after treatment for 3 h, which helped to enhance the inhibitive effect of CU1-LSLN on the proliferation, migration, and invasion potential of MHCC-97H cells and increased its ability to promote apoptosis. Meanwhile, the expression levels of NF-κB, COX-2, MMP-2, MMP-9, and uPA decreased significantly. In vivo, CU1-LSLN prolonged the retention time of the drug, the area under the curve (AUC) increased significantly (CU: 69.9-fold, CU1: 85.9-fold), and no significant liver toxicity was observed. Conclusion: CU1-LSLN is a novel preparation with great potential for treating liver cancer.

Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo.

CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

Glaucoma Is Not Associated With Alzheimer's Disease or Dementia: A Meta-Analysis of Cohort Studies.

Background: Previous studies evaluating the relationships of glaucoma with Alzheimer's disease (AD) and dementia showed inconsistent results. We performed a meta-analysis of cohort studies to evaluate the association between glaucoma with incidence of AD, all-cause dementia, and non-AD dementia. Methods: Cohort studies which evaluated the association between glaucoma with incidence of AD, all-cause dementia, and non-AD dementia in adult population with multivariate analyses were identified by systematic search of PubMed, Embase, and Cochrane's Library databases. A random-effects model incorporating the potential intra-study heterogeneity was used for the meta-analysis. Results: Eleven cohort studies including 4,645,925 participants were included. Results showed that compared to those without glaucoma at baseline, adult patients with glaucoma was not independently associated with increased incidence of AD [adjusted risk ratio (RR): 1.03, 95% confidence interval (CI): 0.93-1.05, P = 0.55; I 2 = 83%], all-cause dementia (adjusted RR: 1.08, 95% CI: 0.97-1.19, P = 0.15; I 2 = 79%), or non-AD dementia (adjusted RR: 1.05 95% CI: 0.91-1.21, P = 0.49; I 2 = 82%). Sensitivity analyses by excluding one study at a time did not significantly affect the results of the meta-analyses. Moreover, subgroup analyses showed consistent results in meta-analysis of prospective or retrospective cohort studies, and in meta-analysis of patients with primary open-angle glaucoma or primary angle-closure glaucoma (P-values for subgroup difference all > 0.05). Conclusions: Current evidence from cohort studies did not support that glaucoma is an independent risk factor of AD, all-cause dementia, or non-AD dementia in adult population.

Gastric floating sustained-release tablet for dihydromyricetin: Development, characterization, and pharmacokinetics study.

Dihydromyricetin (DHM) is a natural dihydroflavonol compound with quite a number of important pharmacological properties. However, its low solubility in water and poor stability in aqueous environment, have compromised drug efficacy of DHM, thus hindering its clinical use. The present study was to develop DHM-loaded gastric floating sustained-release tablet (DHM-GFT) to improve the bioavailability of DHM. DHM-GFT was prepared via powder direct compression. The formulation of tablet was optimized in terms of the floating ability and drug release rate. The optimized DHM-GFT exhibited short floating lag time of less than 10 s and long floating duration of over 12 h in acidic medium. It had a 12-hour sustained release of DHM, which proved its potential to develop as a twice-a-day dosing preparation. The physicochemical properties of DHM-GFT well satisfied the pharmacopoeial requirements. In addition, the results from pharmacokinetic studies demonstrated that, DHM-GFT could considerably prolong the in vivo residence time of drug and improve the bioavailability via good gastric floating ability and sustained drug release when compared to DHM powder. Therefore, DHM-GFT is promising to promote the application of DHM and merits studies for further development.

Diel rhythms of sexual behavior and pheromone titers in Isoceras sibirica Alpheraky (Lepidoptera, Cossidae).

The adult behavior and sex pheromone titers of Isoceras sibirica Alpheraky (Lepidoptera, Cossidae) were investigated to determine the diel periodicity of pheromone production during one scotophase and the effect of age on pheromone production. The results showed that females began to call on the first night after eclosion and called mainly during the second half of scotophase. The percentage of females calling was highest in 1- to 3-day-old females and lowest in 4- to 5-day-old females. The onset of scotophase calling occurred earlier as females aged. The responses to the pheromone source of males aged 1-5 days were monitored in a wind tunnel. Peak activity was observed in 3-day-old males, 4 h after the onset of the scotophase. The mating of all 1- to 3-day-old moths began after 6 h in scotophase and some 4- to 5-day-old moths began during the fourth hour. The average duration of copulation was 34.2 ± 18.2 min (N = 45) and ranged from 17.0 to 56.3 min. Gas chromatography-mass spectrometry (GC-MS) analysis of hexane extracts of pheromone glands revealed that the titers of the three sex pheromone components, (Z)-9-tetradecenyl acetate (Z9-14:Ac), (Z)-7-tetradecenyl acetate, and (Z)-9-hexadecadecenyl acetate were very low on the first night after eclosion, increased and peaked on the second night, then decreased with age. During the first 4 h of the scotophase, titers remained invariant, whereas from 4 to 6 h, pheromone titers increased sharply and peaked, with the greatest peak observed in the primary component, Z9-14:Ac. After the peak, all recorded titers declined until they reached a minimum between the ninth and tenth hours of the dark cycle. In field tests, most of the males were captured in traps during 00:00-02:00 h (13 ± 0.48), and females aged 2 days attracted more males than females of other ages. We infer that the I. sibirica mating system is organized around circadian control of mate calling and mating.

Directional neurite outgrowth on superaligned carbon nanotube yarn patterned substrate.

Superaligned carbon nanotube (CNT) yarn patterned substrates were developed as the topographic scaffold for guiding the neurite outgrowth. As-prepared patterned substrates were used for culturing rat hippocampal neurons, without purifying and functionalizing processes on the CNTs. The neurite outgrowth on the patterned substrate exhibited a strong tendency to being aligned along the CNT yarns long axes. The neurite grown along the CNT yarns had much less branching than the one on a uniform planar substrate typically used for neuron culture. These results indicate that the pure CNT yarns possess the main characteristics of a guidance scaffold for neurite outgrowth. Furthermore, the CNT yarns can be mass produced and be easily weaved into desired structures, which may make them attractive for neuronal regeneration and tissue engineering.

Identification of the sex pheromone of Isoceras sibirica Alpheraky (Lepidoptera, Cossidae).

We discovered that extracts of the female sex pheromone gland of the carpenterworm moth Isoceras sibirica Alpheraky, a pest of Asparagus officinalis Linn., contained (Z)-7-tetradecen-1-ol (Z7-14:OH), (Z)-9-tetradecen-1-ol (Z9-14:OH), (Z)-7-tetradecenyl acetate (Z7-14:Ac), (Z)-9-tetradecenyl acetate (Z9-14:Ac), and (Z)-9-hexadecadecenyl acetate (Z9-16:Ac). The average levels of the chemicals in a single sex pheromone gland of a calling moth were (0.71 +/- 0.24) ng, (1.42 +/- 0.44) ng, (4.36 +/- 0.32) ng, (8.71 +/- 0.26) ng, and (0.82 +/- 0.38) ng, respectively. The electroantennography (EAG) analysis of these chemicals and their analogues demonstrated that Z9-14:Ac triggered significantly the male EAG response. Traps with rubber septa lure impregnated with Z9-14:Ac (500 microg/septum), Z7-14:Ac (250 microg/septum), and Z9-16:Ac (50 microg/septum) were more effective in catching male moths than traps with other baits or virgin females. Addition of Z7-14:OH and Z9-14:OH to rubber septa did not enhance the efficiency of the trap.