Preparation and Evaluation of Novel Supersaturated Solid Dispersion of Magnolol : Theme: Advancements in Amorphous Solid Dispersions to Improve Bioavailability.

This article aimed to design a new type of supersaturated solid dispersion (NS-SD) loaded with Magnolol (Mag) to raise the oral bioavailability in rats. In the light of the solubility parameters, phase solubility experiments, inhibition precipitation experiment, and in vitro release experiment, Plasdone-630 (PS-630) was selected as the optimum carrier. In addition, Mag-NS-SD was prepared by adding Monoglyceride (MG) and Lecithin High Potency (LHP) into the Mag-S-SD (Mag:PS-630 = 1:3), so as to reduce the dosage of carrier and improve the release rate. Using central composite design of response surface method, the prescription was further optimized. As the optimized condition was Mag:PS-630: MG: LHP = 1:3:0.8:0.266, the drug release rate was the fastest. Besides, after 45 min, the release rate was nearly 100%. The constructed Mag-S-SD and Mag-NS-SD were characterized by powder X-ray diffraction and infrared absorption spectrum. The XRD patterns of Mag-S-SD and Mag-NS-SD indicated that all APIs were amorphous. The IR spectra of Mag-S-SD and Mag-NS-SD demonstrated the existence of hydrogen bonding in the systems. Furthermore, in vivo pharmacokinetic study in rats revealed that compared with Mag and Mag-S-SD, Mag-NS-SD significantly increased the bioavailability (the relative bioavailability was 213.69% and 142.37%, separately). In this study, Mag-NS-SD was successfully prepared, which could improve the oral bioavailability and may increase the clinical application.

Wandering spleen torsion with portal vein thrombosis: A case report.

BACKGROUND: Wandering spleen is rare clinically. It is characterized by displacement of the spleen in the abdominal and pelvic cavities and can have congenital or acquired causes. Wandering spleen involves serious complications, such as spleen torsion. The clinical symptoms range from asymptomatic abdominal mass to acute abdominal pain. Surgery is required after diagnosis. Cases of wandering spleen torsion with portal vein thrombosis (PVT) are rare. There is no report on how to eliminate PVT in such cases. CASE SUMMARY: Ultrasound and computed tomography revealed a diagnosis of wandering spleen torsion with PVT in a 31-year-old woman with a history of childbirth 16 mo previously who received emergency treatment for upper abdominal pain. She recovered well after splenectomy and portal vein thrombectomy combined with continuous anticoagulation, and the PVT disappeared. CONCLUSION: Rare and nonspecific conditions, such as wandering splenic torsion with PVT, must be diagnosed and treated early. Patients with complete splenic infarction require splenectomy. Anticoagulation therapy and individualized management for PVT is feasible.

Transfer of Human Microbiome to Drosophila Gut Model.

Laboratory animals with human microbiome have increasingly been used to study the role of bacteria and host interaction. Drosophila melanogaster, as a model of microbiota-host interaction with high reproductive efficiency and high availability, has always been lacking studies of interaction with human gut microbiome. In this study, we attempted to use antibiotic therapy and human fecal exposure strategy to transfer the human microbiome to the drosophila. The method includes depleting the original intestinal bacteria using a broad-spectrum antibiotic and then introducing human microorganisms by a diet supplemented with donor's fecal samples. The sequencing results showed that 80-87.5% of the OTUs (Operational Taxonomic Units) from donor feces were adopted by the recipient drosophila following 30 days of observation. In comparison to females, the male recipient drosophila inherited more microbiota from the donor feces and had significantly increased lifespan as well as improved vertical climbing ability. Furthermore, distinctly differential expression patterns for age and insulin-like signaling-related genes were obtained for the male vs. female recipients. Only the male drosophila offspring acquired the characteristics of the donor fecal microbiota.

Preparation and evaluation of dual drug-loaded nanofiber membranes based on coaxial electrostatic spinning technology.

Wound healing is a complicated process consisting of wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this long-term period, wound is vulnerable to infection by bacteria or microbes. Therefore, we prepared a novel centella total glucoside-ciprofloxacin dual-loaded coaxial nanofiber membrane (CDCNM) by using coaxial electrostatic spinning technique. To satisfy personalized therapeutic demands by adjusting release behaviors, we loaded centella total glucoside (CTG) and ciprofloxacin (CIP) into different positions of the fibers and the morphology and coaxial structure of the nanofiber membranes were analyzed by SEM and TEM. In addition, water contact angle, water absorption capacity, breathability and in vitro drug release were tested. In vitro cell experiments demonstrated that CDCNM can promote fibroblast proliferation. CDCNM demonstrated excellent antimicrobial activity through the agar flat dish diffusion method. Furthermore, rat scald experiments showed that CDCNM significantly accelerated scald healing, meanwhile immunohistochemical staining showed that CDCNM promoted the expression of CD31 and VEGF during early wound healing, which accelerated scald healing by promoting neovascularization and endothelial cell proliferation. As a topical multifunctional wound dressing, this dual drug-loaded nanofiber membrane achieved scald healing effect and continuous bacterial inhibition, which provides new ideas for existing trauma treatment tools and dual drug delivery systems.

Easy Synthesis and Characterization of Novel Carbon Dots Using the One-Pot Green Method for Cancer Therapy.

In this study, hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) were used for the synthesis of novel targeted nanocarrier carbon dots (CDC-H) with photo-luminescence using a one-step hydrothermal method. Doxorubicin (DOX), a common chemotherapeutic agent, was loaded with the CDC-H through electrostatic interactions to form DOX-CDC-H complexes as a targeted antitumor drug delivery system. The synthesized CDC-H show a particle size of approximately 6 nm and a high fluorescence quantum yield of 11.64%. The physical and chemical character properties of CDC-H and DOX-CDC-H complexes were investigated using various techniques. The results show that CDC-H have stable luminescent properties and exhibit excellent water solubility. The in vitro release study showed that DOX-CDC-H exhibited pH-dependent release for 24 h. Confocal laser scanning microscopy was applied to investigate the potential of CDC-H for cell imaging and the cellular uptake of DOX-CDC-H in different cells (NIH-3T3 and 4T1 cells), and the results confirmed the target cell imaging and cellular uptake of DOX-CDC-H by specifically binding the CD44 receptors on the surface of tumor cells. The r MTT results suggest that the DOX-CDC-H complex may induce apoptosis in 4T1 cells, reducing the cytotoxicity of free DOX-induced apoptosis. In vivo antitumor experiments of DOX-CDC-H exhibited enhanced tumor cancer therapy. CDC-H have potential applications in bioimaging and antitumor drug delivery.

Target Controllability in Multilayer Networks via Minimum-Cost Maximum-Flow Method.

In this article, to maximize the dimension of controllable subspace, we consider target controllability problem with maximum covered nodes set in multiplex networks. We call such an issue as maximum-cost target controllability problem. Likewise, minimum-cost target controllability problem is also introduced which is to find minimum covered node set and driver node set. To address these two issues, we first transform them into a minimum-cost maximum-flow problem based on graph theory. Then an algorithm named target minimum-cost maximum-flow (TMM) is proposed. It is shown that the proposed TMM ensures the target nodes in multiplex networks to be controlled with the minimum number of inputs as well as the maximum (minimum) number of covered nodes. Simulation results on Erdos-Rényi (ER-ER) networks, scale-free (SF-SF) networks, and real-life networks illustrate satisfactory performance of the TMM.

Curcumin-loaded sandwich-like nanofibrous membrane prepared by electrospinning technology as wound dressing for accelerate wound healing.

Wound healing is a complicated process constituted of four successive physiological stages involving wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this period, bacteria can easily infect the wound. Therefore, we prepared a novel curcumin-loaded sandwich-like nanofibrous membrane (CSNM) using sequential electrospinning for the hemostasis, antibacterial and accelerate wound healing. The morphology of the nanofibrous membrane was analyzed by SEM. In addition, the water absorption capacity, water vapor transmission rate, water contact-angle, and in vitro drug release were all tested. Then in vitro and in vivo hemostatic experiments demonstrated that CSNM has a good hemostatic effect. Antioxidant effect was assessed by the DPPH radical scavenging method and CSNM presented a high antioxidant activity. Additionally, CSNM demonstrated excellent antibacterial activity by the disk diffusion method. Furthermore, the rat dorsal skin defects model revealed that the CSNM distinctly induced the granulation tissue grew, collagen deposition and epithelial tissue remodeling. Meanwhile, the results of the immunohistochemical staining showed that the CSNM can facilitate the expression of CD31 and TGF-ß in the early stage of the wound, thereby accelerating wound healing. In general, this study proved that the multifunctional CSNM has great potential as wound dressing in wound healing.

A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence.

Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.

2-Keto-L-Gulonic Acid Improved the Salt Stress Resistance of Non-heading Chinese Cabbage by Increasing L-Ascorbic Acid Accumulation.

Salt stress has long been a prominent obstacle that restricts crop growth, and increasing the L-ascorbic acid (ASA) content of crops is an effective means of alleviating this stress. 2-Keto-L-gulonic acid (2KGA) is a precursor used in industrial ASA production as well as an ASA degradation product in plants. However, to date, no study has investigated the effects of 2KGA on ASA metabolism and salt stress. Here, we evaluated the potential of using 2KGA to improve crop resistance to salt stress (100mM NaCl) through a cultivation experiment of non-heading Chinese cabbage (Brassica campestris ssp. chinensis). The results showed that the leaf and root biomass were significantly improved by 2KGA application. The levels of metabolites and enzymes related to stress resistance were increased, whereas the hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents were decreased. Lipid peroxidation and cell membrane damage were alleviated following 2KGA treatment. Positive correlations were found between photosynthetic pigments and organic solutes, ASA and photosynthetic pigments, and ASA and antioxidant enzymes. In contrast, negative correlations were observed between antioxidant enzymes and H2O2/MDA. Moreover, the expression levels of L-gulono-1,4-lactone oxidase, GDP-mannose pyrophosphorylase, dehydroascorbate reductase-3, and ascorbate peroxidase were increased by 2KGA treatment. These results suggested that exogenous 2KGA application can relieve the inhibitory effect of salt stress on plant growth, and the promotion of ASA synthesis may represent a critical underlying mechanism. Our findings have significant implications for the future application of 2KGA or its fermentation residue in agriculture.

Olfactory fMRI Activation Pattern Across Different Concentrations Changes in Alzheimer's Disease.

The olfactory involvement is an early feature of Alzheimer's disease (AD). Olfactory functional MRI (fMRI) is an objective method to evaluate the olfactory function, but might be affected by the individual variation and the magnetic susceptibility artifact of basis cranii. To improve the reliability of olfactory fMRI, we explored the response of primary olfactory cortex (POC) across three different concentrations of odors. Fourty-four normal controls, 46 subjects with mild cognitive impairment (MCI), and 44 patients with AD underwent olfactory fMRI using lavender stimuli of three different (0.10, 0.33, and 1.00%) concentrations during one fMRI sequence with a 3.0T MRI scanner. The numbers of activated voxels in the POC, especially the activation changes during different concentrations were, analyzed. The POC activation pattern of controls showed olfactory adaptation at the higher concentration, whereas the AD patients showed not only increased olfactory threshold but also a lack of olfactory habituation. Five types of activation patterns across different concentrations were summarized to evaluate the olfactory function. The results showed that the activation pattern effectively found 40/44 (90.9%) of the ADs with impaired habituation, whereas 31/44 (70.5%) of the normal controls showed normal olfactory habituation. In MCIs, 29/46 (63.0%) of subjects showed impaired habituation. This finding indicates that the POC activation pattern of olfactory fMRI across different concentrations is useful in evaluating the olfactory function, which is important in the detection of early AD among MCI cases.

Non-Gaussian diffusion alterations on diffusion kurtosis imaging in patients with early Alzheimer's disease.

OBJECTIVE: To evaluate non-Gaussian diffusion changes of the whole-brain and its correlation with cognitive performance in patients with early Alzheimer's disease (AD), using diffusion kurtosis imaging (DKI). METHODS: Twenty-six patients with early AD and twenty-six normal controls underwent diffusion imaging. Seven parametric maps were calculated from multiple b-value diffusion data, including mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD) and radial diffusivity (RD). Voxel-based analyses were performed to evaluate the group difference between the AD patients and normal controls. Then correlation between the diffusion parameters (MK, FA and MD) and cognitive performance were analyzed in AD patients. RESULTS: For AD patients, increased MD, AxD and RD were found in white matter (WM), including the genu of corpus callosum, bilateral cingulate bundle, bilateral temporal and frontal WM, and were also found in gray matter (GM), including the bilateral temporal GM, parahippocampal gyrus, hippocampus, cingulate gyrus, thalamus, and amygdala. These regions were partially overlapped with those showing decreased FA, MK, AK and RK. However, only kurtosis indices could detect the significant differences in the lentiform nucleus between AD patients and health control. DKI indices in AD patients significantly correlated with the clinical scores in genu of CC, cingulate bundle, temporal and frontal lobe, while the voxel number showing significant correlation with MK was more than that with FA and MD. CONCLUSIONS: Early AD patients already have microstructural changes in both WM and GM. DKI can provide supplementary information in reflecting these changes and may be sensitive in diagnosing early AD.

Background rhythm frequency and theta power of quantitative EEG analysis: predictive biomarkers for cognitive impairment post-cerebral infarcts.

In clinical settings, cerebral infarct is a common disease of older adults, which usually increases the risk of cognitive impairment. This study aims to assess the quantitative electroencephalography (qEEG) as a predictive biomarker for the development of cognitive impairment, post-cerebral infarcts, in subjects from the Department of Neurology. They underwent biennial EEG recording. Cerebral infarct subjects, with follow-up cognitive evaluation, were analyzed for qEEG measures of background rhythm frequency (BRF) and relative δ, θ, α, and ß band power. The relationship between cognitive impairment and qEEG, and other possible predictors, was assessed by Cox regression. The results showed that the risk hazard of developing cognitive impairment was 14 times higher for those with low BRF than for those with high BRF (P < .001). Hazard ratio (HR) was also significant for more than median θ band power (HR = 5, P = .002) compared with less than median θ band power. The HRs for δ, α, and ß bands were equal to the baseline demographic, and clinical characteristics were not significantly different. In conclusion, qEEG measures of BRF, and relative power in θ band, are potential predictive biomarkers for cognitive impairment in patients with cerebral infarcts. These biomarkers might be valuable in early prediction of cognitive impairment in patients with cerebral infarcts.