Curative effect of medicine cake sticking ultrasound drug penetration combined with body training on hemiplegia after stroke: An in vitro ultrasound targeted drug controlled release technology.

To explore the efficacy of ultrasound drugs in the treatment of hemiplegia after stroke. The evaluation included clinical symptoms and signs, the Stroke Scale, activities of daily living, sensory disorder Fugl-Meyer and Lindmark, electromyography sensory nerve amplitude, and conduction velocity indexes in both groups. There was no significant difference in the improved Fugl-Meyer and Lindmark score between treatment (26.97 ± 2.78) and the control group (27.45 ± 3.1) (t = 14.528, P = 0.593). After treatment, the observation group (37.10 ± 4.2) was significantly different from the control group (34.76 ± 4.36) (t = 11.259, P = 0.005) and (t = 10.15 ± 1.69), (40.87 ± 6.58) (t = 7.943,9.538, P = 0.564,0.826). After treatment, the observation group the Stroke Scale (4.27 ± 0.57), activities of daily living score (76.15 ± 12.38) and the control group (5.36 ± 0.89), (58.41 ± 9.69) (t = 16.274,5.379, P = 0.035,0.000) after treatment and F wave and M wave. The cure rate of the observation group was 77.50% (31/40), which was significantly better than that of the control group, 47.50% (19/40), with a significant difference (χ2 = 11.724,P = 0.000). After comparison, the total response rate of the observed group reached 92.500% (37 / 40), which was significantly higher than the 80.00% (32 / 40) of the control group. This difference was statistically significant (χ 2 = 9.458, P = 0.015). This therapy closely links the theoretical knowledge of modern medicine with the theoretical knowledge of traditional Chinese medicine, and uses the meridian theory to give full play to the unique advantages of traditional Chinese medicine.

Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway.

In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the expression of phospho-AMP-activated protein kinase (p-AMPK) proteins to inhibit the expression of the sterol regulatory element binding protein-1c (SREBP-1c) proteins on increasing lipid synthesis and up-regulating the expression of the PPAP-α and CPT-1 proteins on promoting the ß-oxidation of fatty acids. Moreover, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) can significantly inhibit reactive oxygen species' (ROS) production, promote the activities of intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; and catalase, CAT) and bring down the content of malondialdehyde (MDA) derived from lipid peroxidation. Further investigations revealed that the regulation of these five oligopeptides on oxidative stress was achieved through activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to raise the expression levels of the heme oxygenase 1 (HO-1) protein and downstream antioxidant proteases. Therefore, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) could serve as candidate ingredients to develop functional products for treating NAFLD.

Eighteen Novel Bioactive Peptides from Monkfish (Lophius litulon) Swim Bladders: Production, Identification, Antioxidant Activity, and Stability.

In the study, papain was chosen from five proteases to hydrolyze proteins of monkfish swim bladders for effectively utilizing monkfish (Lophius litulon) processing byproducts, and the hydrolysis conditions of papain were optimized as hydrolysis temperature of 65 °C, pH 7.5, enzyme dose 2.5% and time 5 h using single-factor and orthogonal experiments. Eighteen peptides were purified from the swim bladder hydrolysate of monkfish by ultrafiltration and gel permeation chromatography methods and identified as YDYD, QDYD, AGPAS, GPGPHGPSGP, GPK, HRE, GRW, ARW, GPTE, DDGGK, IGPAS, AKPAT, YPAGP, DPT, FPGPT, GPGPT, GPT and DPAGP, respectively. Among eighteen peptides, GRW and ARW showed significant DPPH· scavenging activities with EC50 values of 1.053 ± 0.003 and 0.773 ± 0.003 mg/mL, respectively; YDYD, QDYD, GRW, ARW and YPAGP revealed significantly HO· scavenging activities with EC50 values of 0.150 ± 0.060, 0.177 ± 0.035, 0.201 ± 0.013, 0.183 ± 0.0016 and 0.190 ± 0.010 mg/mL, respectively; YDYD, QDYD, ARW, DDGGK and YPAGP have significantly O2-· scavenging capability with EC50 values of 0.126 ± 0.0005, 0.112 ± 0.0028, 0.127 ± 0.0002, 0.128 ± 0.0018 and 0.107 ± 0.0002 mg/mL, respectively; and YDYD, QDYD and YPAGP showed strong ABTS+· scavenging ability with EC50 values of 3.197 ± 0.036, 2.337 ± 0.016 and 3.839 ± 0.102 mg/mL, respectively. YDYD, ARW and DDGGK displayed the remarkable ability of lipid peroxidation inhibition and Ferric-reducing antioxidant properties. Moreover, YDYD and ARW can protect Plasmid DNA and HepG2 cells against H2O2-induced oxidative stress. Furthermore, eighteen isolated peptides had high stability under temperatures ranging from 25-100 °C; YDYD, QDYD, GRW and ARW were more sensitive to alkali treatment, but DDGGK and YPAGP were more sensitive to acid treatment; and YDYD showed strong stability treated with simulated GI digestion. Therefore, the prepared antioxidant peptides, especially YDYD, QDYD, GRW, ARW, DDGGK and YPAGP from monkfish swim bladders could serve as functional components applied in health-promoting products because of their high-antioxidant functions.

Alterations in intrinsic functional networks in Parkinson's disease patients with depression: A resting-state functional magnetic resonance imaging study.

AIMS: The aim of this research was to investigate the alterations in functional brain networks and to assess the relationship between depressive impairment and topological network changes in Parkinson's disease (PD) patients with depression (DPD). METHODS: Twenty-two DPD patients, 23 PD patients without depression (NDPD), and 25 matched healthy controls (HCs) were enrolled. All participants were examined by resting-state functional magnetic resonance imaging scans. Graph theoretical analysis and network-based statistic methods were used to analyze brain network topological properties and abnormal subnetworks, respectively. RESULTS: The DPD group showed significantly decreased local efficiency compared with the HC group (P = .008, FDR corrected). In nodal metrics analyses, the degree of the right inferior occipital gyrus (P = .0001, FDR corrected) was positively correlated with the Hamilton Depression Rating Scale scores in the DPD group. Meanwhile, the temporal visual cortex, including the bilateral middle temporal gyri and right inferior temporal gyrus in the HC and NDPD groups and the left posterior cingulate gyrus in the NDPD group, was defined as hub region, but not in the DPD group. Compared with the HC group, the DPD group had extensive weakening of connections between the temporal-occipital visual cortex and the prefrontal-limbic network. CONCLUSIONS: These results suggest that PD depression is associated with disruptions in the topological organization of functional brain networks, mainly involved the temporal-occipital visual cortex and the posterior cingulate gyrus and may advance our current understanding of the pathophysiological mechanisms underlying DPD.

Antioxidant Peptides from Collagen Hydrolysate of Redlip Croaker (Pseudosciaena polyactis) Scales: Preparation, Characterization, and Cytoprotective Effects on H2O2-Damaged HepG2 Cells.

Bioactive peptides from fish collagens with antioxidant properties have become a topic of great interest for health, food, and processing/preservation industries. To explore the high-value utilized way of scales produced during the fish processing, collagen hydrolysates of redlip croaker (Pseudosciaena polyactis) scales were prepared using six different proteases, and the hydrolysate (RSCH) prepared using neutrase showed the highest degree of hydrolysis (21.36 ± 1.18%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging activity (30.97 ± 1.56%) among the six hydrolysates. Subsequently, six antioxidant peptides were purified from RSCH using membrane ultrafiltration and serial chromatography, and their amino acid sequences were identified as DGPEGR, GPEGPMGLE, EGPFGPEG, YGPDGPTG, GFIGPTE, and IGPLGA with molecular masses of 629.61, 885.95, 788.96, 762.75, 733.80, and 526.61 Da, respectively. Among six collagen peptides, GPEGPMGLE, EGPFGPEG, and GFIGPTE exhibited the strongest scavenging activities on DPPH· radical (EC50 0.59, 0.37, and 0.45 mg/mL), hydroxyl radical (EC50 0.45, 0.33, and 0.32 mg/mL), and superoxide anion radical (EC50 0.62, 0.47, and 0.74 mg/mL). GPEGPMGLE, EGPFGPEG, and GFIGPTE showed high inhibiting ability on lipid peroxidation in a linoleic acid model system and protective activities on oxidation-damaged DNA. More importantly, GPEGPMGLE, EGPFGPEG, and GFIGPTE could protect HepG2 cells from H2O2-induced oxidative damage through decreasing the levels of reactive oxygen species (ROS) and MDA and activating intracellular antioxidant enzymes of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). These results suggested that six collagen peptides (RCP1-RCP6), especially GPEGPMGLE, EGPFGPEG, and GFIGPTE, might serve as potential antioxidants applied in nutraceutical and pharmaceutical products.

Genetic characterization of porcine kobuvirus variants identified from healthy piglets in China.

In this study, two porcine kobuvirus strains, JS-01-CHN and JS-02a-CHN were detected from piglets with diarrhea and asymptomatic, respectively. The sequences of the two strains were analyzed using a bioinformatics software package. The full-length genome of JS-02a-CHN, was detected in healthy piglets was 8121 nucleotides (nt) long excluding the poly(A) tail. There was a 30 amino acid deletion in the 2B-coding region of JS-02a-CHN. We are the first to report a 30 amino acid deletion in porcine kobuvirus from asymptomatic piglets, indicating that porcine kobuvirus may have evolved differently based on geography and host differences. Fecal samples were obtained from pigs with diarrhea (n=91) and healthy (n=126) pigs and analyzed using RT-PCR. Of these, 64.8% (59/91) of diarrheic piglets and 19.8% (25/126) of healthy piglets were positive for PKV using VP1 specific primers. Twenty-eight (28) virus positive samples were randomly selected and the VP1 gene was analyzed. Phylogenetic analysis indicated that the 15 strains isolated from pigs with diarrhea clustered into different branches, while the VP1 sequences from clinically healthy pigs clustered into a single large group. These results indicate that the VP1 gene is diverse in pigs with diarrhea but conserved in healthy pigs in the Jiangsu Province.

A fusion protein composed of receptor binding domain of vascular endothelial growth factor-A and constant region fragment of antibody: angiogenesis antagonistic activity.

Vascular endothelial growth factor (VEGF) promotes the growth of solid tumor mainly via VEGF receptor-1 and receptor-2, which are expressed preferentially in proliferating endothelial cells. Therefore, a strategy for simultaneous blockage of both VEGF receptors may have a useful therapeutic effect in tumor growth. In this study, we utilized a fusion protein which is composed of receptor binding domain of VEGF-A (RBDV) and the constant region fragment (Fc) of a human immunoglobulin G1 (IgG1), to interfere with the growth of human umbilical vein endothelial cells (HUVECs) via VEGF receptors. The results showed that RBDV-IgG1 Fc was able to bind with both VEGF receptor-1 and receptor-2. In addition, RBDV-IgG1 Fc could decrease VEGF-induced proliferation and tube formation among HUVECs. Moreover, the cytotoxic test showed RBDV-IgG1 Fc could also enhance the cytotoxic activity of human natural killing cells. The data are suggesting that the fusion protein, RBDV-IgG1 Fc, may have potential as an angiogenesis antagonist for future tumor therapy.

A rapid method for creating drug implants: translating laboratory-based methods into a scalable manufacturing process.

Low compliance with medication is the major cause of poor outcome in schizophrenia treatment. While surgically implantable solvent-cast pellets were produced to improve outcome by increased compliance with medication, this process is laborious and time-consuming, inhibiting its broader application (Siegel et al., Eur J Pharm Biopharm 2006;64:287-293). In this study, the previous fabrication process was translated to a continuous and scalable extrusion method. Extrusion processes were modified based on in vitro release studies, drug load consistency examination, and surface morphology analysis using scanning electron microscopy. Afterward, optimized haloperidol implants were implanted into rats for preliminary analysis of biocompatibility. Barrel temperature, screw speed and resulting processing pressure influenced surface morphology and drug release. Data suggest that fewer surface pores shift the mechanism from bulk to surface PLGA degradation and longer lag period. Results demonstrate that extrusion is a viable process for manufacturing antipsychotic implants.

[Cloning and polymorphism analysis of SmERF in Salvia miltiorrhiza].

The transcription factor of ethylene responsive factor binding protein (ERF) is belonged to AP2/ERF superfamily, which is known to be unique in plants. AP2/ERF proteins have important functions in the transcriptional regulation of a variety of biological processes related to growth and development, as well as various responses to environmental stimuli. An ERF gene from Salvia miltiorrhiza is cloned and divided into ERF gene family group VII of Arabidopsis and Rice. It contains a MCGGAI (I/L) motif referred to as CMVII-1 and a single intron in the 5'-flanking region of the AP2/ERF domain. Sequence analysis reveals that the region of second extron has abundant polymorphism sites. There are 21 single nucleotide polymorphism sites (SNPs) in the 264 bp region, among them, 14 SNPs are synonymous substitutions and 7 SNPs are non-synonymous substitutions. Though analysis of 181 samples from Shandong, Shaanxi and Sichuan Provinces, it reveals that each production area has its own special genotypes, 5 SNPs show significant difference. Cluster based on UPGMA method reveals that different populations from specific province have clustered together. It shows that SmERF gene will be a candidate molecular marker for the identification of Salvia miltiorrhiza from different areas.

Identification and characterization of oligonucleotides that inhibit Toll-like receptor 2-associated immune responses.

Toll-like receptors (TLRs) play important roles in the immune responses against invading microorganisms. Development of TLR antagonists is recognized as a promising direction in suppressing the associated inflammatory reactions of the TLRs. Aptamers are single-stranded RNA or DNA molecules isolated through an in vitro selection process. Using a novel molecular evolution strategy that combines immunoprecipitation (IP) with systematic evolution of ligands by exponential enrichment (SELEX), we developed an IP-SELEX selection method to facilitate the screening of high-affinity aptamers for the Toll-like receptor 2 (TLR2). Also, human TLR2 functional aptamers were identified and characterized using NF-kappaB reporter assays. Among the functional aptamers, the most effective, AP177, with a dissociation constant of 73 pM, was characterized with TLR2-expressing cells challenged with bacterial cells and purified ligands. The aptamer could effectively antagonize TLR2, significantly inhibit NF-kappaB activity, and suppress the secretion of the cytokines by >80%. In addition, the precise region within the functional aptamer that specifically bound TLR2 was resolved using aptamer microarray analysis. The results of functional assays showed that AP177 acted as a TLR2 antagonist and may hold therapeutic potential in the treatment of diseases related to dysregulated TLR2 immune responses.