Bioactive Components of Lycium barbarum and Deep-Processing Fermentation Products.

Lycium barbarum, a homology of medicine and food, contains many active ingredients including polysaccharides, polyphenol, betaine, and carotenoids, which has health benefits and economic value. The bioactive components in Lycium barbarum exhibit the effects of antioxidation, immune regulation, hypoglycemic effects, and vision improvement. Recently, the development of nutrition and health products of Lycium barbarum has been paid more and more attention with the increase in health awareness. A variety of nutrients and bioactive components in wolfberry can be retained or increased using modern fermentation technology. Through fermentation, the products have better flavor and health function, which better meet the needs of market diversification. The main products related to wolfberry fermentation include wolfberry fruit wine, wolfberry fruit vinegar, and lactic acid fermented beverage. In this review, the mainly bioactive components of Lycium barbarum and its deep-processing products of fermentation were summarized and compared. It will provide reference for the research and development of fermented and healthy products of Lycium barbarum.

Changes in the Phytochemical and Bioactive Compounds and the Antioxidant Properties of Wolfberry during Vinegar Fermentation Processes.

Wolfberry (Lycium barbarum L.), as a kind of functional fruit, has various nutritional and bioactive components, which exhibit healthy benefits. However, wolfberry is not easy to preserve, and the intensive processing of wolfberry needs to be developed. In the present study, the changes in the phytochemical and bioactive compounds, as well as the antioxidant properties of wolfberry, were evaluated in the brewed processes. We found that the sugar contents were significantly decreased, and the total acids values were significantly increased during the fermentation processes. The sugar and fat contents were low in the wolfberry fruit vinegar after fermentation, which is of benefit to human health. In addition, amino acids were examined during the fermentation processes, and histidine, proline, and alanine were found to be the main amino acids in vinegar. The total phenolics and flavonoids contents were significantly increased by 29.4% and 65.7% after fermentation. 4-Hydroxy benzoic acid, 3-hydroxy cinnamic acid, and chlorogenic acid were the primary polyphenols in the wolfberry fruit vinegar. Moreover, the antioxidant activity of wolfberry fruit vinegar was significantly increased compared with that of wolfberry fruit after the fermentation processes. Polysaccharides and polyphenolics were strongly correlated with the antioxidant activity during the fermentation processes. The findings suggest that wolfberry fruit vinegar has a high antioxidant capability, and could be a beneficial food in the human diet.

Cigarette smoke exposed airway epithelial cell-derived EVs promote pro-inflammatory macrophage activation in alpha-1 antitrypsin deficiency.

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder most commonly secondary to a single mutation in the SERPINA1 gene (PI*Z) that causes misfolding and accumulation of alpha-1 antitrypsin (AAT) in hepatocytes and mononuclear phagocytes which reduces plasma AAT and creates a toxic gain of function. This toxic gain of function promotes a pro-inflammatory phenotype in macrophages that contributes to lung inflammation and early-onset COPD, especially in individuals who smoke cigarettes. The aim of this study is to determine the role of cigarette exposed AATD macrophages and bronchial epithelial cells in AATD-mediated lung inflammation. METHODS: Peripheral blood mononuclear cells from AATD and healthy individuals were differentiated into alveolar-like macrophages and exposed to air or cigarette smoke while in culture. Macrophage endoplasmic reticulum stress was quantified and secreted cytokines were measured using qPCR and cytokine ELISAs. To determine whether there is "cross talk" between epithelial cells and macrophages, macrophages were exposed to extracellular vesicles released by airway epithelial cells exposed to cigarette smoke and their inflammatory response was determined. RESULTS: AATD macrophages spontaneously produce several-fold more pro-inflammatory cytokines as compared to normal macrophages. AATD macrophages have an enhanced inflammatory response when exposed to cigarette smoke-induced extracellular vesicles (EVs) released from airway epithelial cells. Cigarette smoke-induced EVs induce expression of GM-CSF and IL-8 in AATD macrophages but have no effect on normal macrophages. Release of AAT polymers, potent neutrophil chemo attractants, were also increased from AATD macrophages after exposure to cigarette smoke-induced EVs. CONCLUSIONS: The expression of mutated AAT confers an inflammatory phenotype in AATD macrophages which disposes them to an exaggerated inflammatory response to cigarette smoke-induced EVs, and thus could contribute to progressive lung inflammation and damage in AATD individuals.

Nutrition, Bioactive Components, and Hepatoprotective Activity of Fruit Vinegar Produced from Ningxia Wolfberry.

Wolfberry (Lycium barbarum L.) is a nutritious and medicinal fruit, and deeply processed products of wolfberry needs to be improved. In this study, nutrition, bioactive compounds, and hepaprotective activity were explored in wolfberry vinegar (WFV). The contents of nutrients including total sugar and protein in WFV samples were 2.46 and 0.27 g/100 mL, respectively. Total phenolic and flavonoid contents in WFV were 2.42 mg GAE/mL and 1.67 mg RE/mL, respectively. p-Hydroxybenzoic acid and m-hydroxycinnamic acid were the main polyphenols in WFV. The antioxidant activity of WFV were 20.176 mM Trolox/L (ABTS), 8.614 mM Trolox/L (FRAP), and 26.736 mM Trolox/L (DPPH), respectively. In addition, WFV treatment effectively alleviated liver injury by improving histopathological changes and reducing liver biochemical indexes in CCl4-treated mice. WFV alleviated oxidative damage by inhibiting oxidative levels and increasing antioxidant levels. These results suggest that WFV can be utilized as a functional food to prevent oxidative liver injury.

Application of Diffusion Kurtosis Imaging in Evaluating Acute Xerostomia in Nasopharyngeal Carcinoma Treated With Induction Chemotherapy Plus Concurrent Chemoradiotherapy.

Purpose: The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Methods: The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded. Results: At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433). Conclusion: DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.

Association between fecal microbiota and generalized anxiety disorder: Severity and early treatment response.

BACKGROUND: Associations between abnormal gut microbiome compositions and anxiety-like behaviors are well established. However, it is unknown whether the gut microbiome composition is associated with the severity of generalized anxiety disorder (GAD) and relief from clinical symptoms in patients. METHODS: Stool samples from 36 patients with active GAD (A-GAD group) and 24 matched healthy control subjects (HC group) were analyzed by 16S rRNA gene sequencing. Anxiety was assessed with the Hamilton Anxiety Rating Scale and the Self-rating Anxiety Scale, and global assessments of functioning were performed at baseline and 1 month after drug treatment. RESULTS: Gut microbiome compositions were altered in A-GAD patients, with fewer operational taxonomic units and lower fecal bacterial α-diversity. Specifically, Firmicutes and Tenericutes abundances were lower in A-GAD patients, and several genera were differentially represented in the A-GAD and HC groups. The abundances of Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-014, and Prevotella_9 correlated negatively with the anxiety severity and positively with anxiety reduction, whereas the abundances of Bacteroides and Escherichia-Shigella were positively associated with anxiety severity. Sex, smoking, and alcohol intake influenced the gut microbiome composition. LIMITATIONS: The sample sizes were small and the stool samples were collected only at baseline; therefore, a causal association between changes in intestinal flora and disease remission was not established. Moreover, the effects of different drugs on gut microbiome composition were not investigated. CONCLUSIONS: Altered gut microbiome composition may contribute to GAD pathogenesis and remission.

[Acetabular cup position on high hip and anatomical position in total hip arthroplasty for Crowe III developmental dysplasia of hip joint].

OBJECTIVE: To evaluate clinical outcomes of acetabular cup position on high hip and anatomical position in total hip arthroplasty for Crowe III developmental dysplasia of hip joint. METHODS: Forty-six patients(58 hips) treated with high hip center THA from January 2010 to December 2015, including 6 males (8 hips) and 40 females(50 hips) aged from 40 to 70 years old with an average of(54.3±7.6) years old. While 20 patients(28 hips) treated with anatomical position in THA from January 2004 and December 2009 were analyzed as control, including 4 males (5 hips) and 16 females (23 hips), aged from 42 to 68 years old with an average of (53.0±7.1) years old. Operative time, blood loss, Harris score (HHS), gait analysis, Trendelanburg signal, imaging examinations and prosthesis survivorship were compared between two groups. RESULTS: Operative time and blood loss in high hip group(75.1±13.3) min and (108.4±47.1) ml respectively were lower than that of in anatomical position group(107.7±17.1) min and(201.0±58.6) ml respectively. There was no statistical difference in HSS score at 2 years after operation in high hip group(92.3±3.7) scores and anatomical position group(91.4±3.6) scores. No obvious meaning in lower limb differences in high hip group (3.8±2.1) mm and anatomical position group (3.5±1.6) mm. The vertical distance between center of rotation to teardrop in high hip group(31.6±7.8) mm was higher than that of anatomical group(19.3±7.4) mm;while there was no significant differences in horizontal distance between high hip group (30.1±7.7) mm and anatomical group(29.4±7.5) mm. There was no statistical significance in prosthesis survivorship. The gait was good without lameness and positive features of Trendelanburg signal caused by insufficient of abductor. CONCLUSIONS: For Crowe III DDH, a high hip center cementless cup without bone graft is a liable method with good function and high rate of prosthesis survivorship. And satisfying short-term clinical and radiographic results could be achieved by this method.

Design, synthesis, and biological evaluation of scutellarein carbamate derivatives as potential multifunctional agents for the treatment of Alzheimer's disease.

A series of scutellarein carbamate derivatives were designed and synthesized based on the multitarget-directed drug design strategy for treatment of Alzheimer's disease. Their acetylcholinesterase and butyrylcholinesterase inhibitory activities, antioxidant activities, metals chelation, and neuroprotective effects against hydrogen peroxide-induced PC12 cell injury were evaluated in vitro. The preliminary results indicated that compound 7b exhibited good inhibitory potency toward AChE and BuChE with IC50 values of 1.2 ± 0.03 µm and 22.1 ± 0.15 µm, respectively, possessed the strong antioxidant potency (10.3 trolox equivalents), as well as acted as a selective metal chelator and neuroprotective agent. Furthermore, 7b could improve memory impairment induced by scopolamine, ethanol, and sodium nitrite using the step-down passive avoidance task in vivo and could remarkably decrease the activity of acetylcholinesterase in mice brain. This study indicated that 7b could be considered as a potential multitarget agent against AD.

miR-20a promotes prostate cancer invasion and migration through targeting ABL2.

The aberrant expression of microRNAs (miRNAs) has been found in various types of cancer. The present study found miR-20a was significantly up-regulated in prostate cancer compared with normal prostate tissues. Patients with a higher miR-20a expression had a Gleason score of 7-10 and shorter survival time. The transwell and wound healing assays revealed that blocking expression of miR-20a by miR-20a ASO suppresses the invasion and migration of PC-3 and DU145 cells in vitro and also inhibits tumor growth in vivo. Furthermore, we identified miR-20a directly targets the ABL family non-receptor tyrosine kinases ABL2 and negatively regulates the phosphorylation of its downstream gene p190RhoGAP. Knockdown of ABL2 promoted cell invasion and migration and we identified miR-20a-induced cell invasion and migration can be rescued by ABL2. In conclusion, our findings show that miR-20a significantly contributes to the progression of prostate cancer by targeting ABL2.

Differential proteomic analysis of nasal polyps, chronic sinusitis, and normal nasal mucosa tissues.

OBJECTIVE: To compare protein expression in nasal polyps, chronic sinusitis, and normal nasal mucosa tissues using proteomic technology. DESIGN: Cross-sectional survey. SUBJECTS AND METHODS: Proteins extracted from the three kinds of tissues (seven samples per group) were separated by immobilized pH4-7 gradient two-dimensional gel electrophoresis (2-DE). PDQuest software was used to analyze 2-DE images, and the differentially expressed protein spots were identified with the use of both MALDI-TOF-MS and ESI-Q-TOF-MS. Of the differentially expressed proteins, Cu/ZnSOD and PLUNC were validated with the use of immunohistochemical tests. RESULTS: High-resolution, reproducible 2-DE patterns were obtained, and 30 differentially expressed protein spots were found. The intensity of Cu/ZnSOD and PLUNC differed significantly on immunohistochemical validation. CONCLUSION: These differentially expressed proteins are involved in airway inflammatory reaction, immune response, oxidative stress, and metabolic reaction after exposure to irritants. In the future, several of these proteins may prove useful for exploring the pathogenesis of nasal polyps and chronic sinusitis or as objective biomarkers for quantitatively monitoring disease progression or response to therapy.

Cloning and characterization of four B-hordein genes from Tibetan hull-less barley (Hordeum vulgare subsp. vulgare).

Four B-hordein genes, designated BH1-BH4, were cloned using PCR amplification from two hull-less barley cultivars, ZQ7239 and ZQ148, collected from Tibet. The results of sequencing indicated that BH1-BH4 contained complete open reading frames (ORFs). Comparison of their predicted polypeptide sequences with the published sequences suggested that they all share the same basic protein structure. Phylogenetic analysis indicated that the deduced amino-acid sequences of BH1-BH4 genes were more closely related to B-hordeins from cultivated barley (Hordeum vulgare L.) than to any other prolamins from wild barley and Aegilops tauschii. Comparison of the coding regions of BH1-BH4 genes showed that BH1 had a lower sequence identity to other previously published B-hordeins than the other three B-hordeins obtained in this study. BH1 was then cloned in a bacterial expression vector based on bacteriophage T7 RNA polymerase. The resulting plasmid produced a 28.15 kDa protein in Escherichia coli. The potential value of B-hordein genes in grain quality improvement of hull-less barley has been discussed.

Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro.

AIM: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. METHODS: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPE-LC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-(127)I iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC(50)) of sifuvirtide on cell fusion was determined by co-cultivation assay. RESULTS: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 microg/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10 626+/-2886 microg/L and 528+/-191 microg/L, and the terminal elimination half-lives (T(1/2)) were 6.3+/-0.9 h and 5.5+/-1.0 h, respectively. After sc, T(max) was 0.25-2 h, and the absolute bioavailability was 49%+/-13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC(50) of 0.33 microg/L. CONCLUSION: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T(1/2) of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC(50) in vitro.