Astragaloside IV Inhibits the Proliferation of Human Uterine Leiomyomas by Targeting IDO1.

Astragaloside IV (AS-IV) is a chemical found in traditional Chinese medicine called Astragalus membranaceus (Fisch.) Bunge that has antitumor properties. However, the roles and mechanisms of AS-IV in uterine leiomyomas (ULMs) are unclear. The immunosuppressive enzyme indoleamine-2,3-dioxygenase-1 (IDO1) is involved in tumor formation. IDO1 is a new and reliable prognostic indicator for several cancers. In this work, AS-IV was applied to ULM cells in various concentrations. CCK-8, immunofluorescence, and flow cytometry were used to examine the proliferation and apoptosis of ULM cells caused by AS-IV. After lentiviral vector transduction with IDO1 short hairpin RNA (shRNA), the knockdown and overexpression of IDO1 were stable in ULM cells. To verify the antitumor effect of AS-IV in vivo, we established a rat model of uterine leiomyoma. HE staining, Masson staining, and transmission electron microscopy were used to observe pathological changes in the uterus, and the levels of serum sex hormones were measured by radio immune assay (RIA). The levels of CD3+T, CD4+T, and CD25+ Foxp3+Treg in rat peripheral blood were detected by flow cytometry. Western blotting and immunohistochemistry were used to examine protein expression. We found that AS-IV dramatically increased the apoptotic rate of ULM cells and reduced viability in a time- and dosage-dependent manner. After sh-IDO1 lentiviral transfection, we discovered that knocking down IDO1 reversed the effects of AS-IV on ULM cell proliferation and autophagy. We also found that AS-IV can effectively inhibit the growth of ULMs in vivo. AS-IV may promote apoptosis and autophagy in ULMs by activating PTEN/PI3K/AKT signaling through inhibition of IDO1. These findings imply that AS-IV exerts antifibroid effects, and the underlying mechanism may be IDO1, which is involved in proliferation, apoptosis, and autophagy.

A comprehensive analysis of the components of common weed pollen and related allergens in patients with allergic diseases in southern China.

BACKGROUND: Pollen allergens are vital contributors to allergic diseases. The frequency and coreactivity pattern of allergens are closely related to geographical distribution. OBJECTIVE: In this study, we aimed to characterize the prevalence of the molecular components of the common weed pollen allergens, birch pollen, walnut, and cross-reactive carbohydrate determinant (CCD), as well as investigate the relationship between the allergens and CCD in Chinese pollen-sensitized patients with allergic diseases. METHODS: Based on previous vegetation surveys, serum samples from 165 pollen-sensitized patients with allergic diseases in Guangdong Province in southern China were used to test 19 crude allergen extracts, their components, and CCD using component-resolved diagnosis (CRD). Moreover, the potential associations among CCD, allergens, and their components were described. RESULTS: In the 165 samples, the most common sensitized allergens were goosefoot (43.0%), ragweed (40.6%), walnut (37.6%), walnut tree (37.6%), and mugwort (37.0%), followed by platane (35.2%), cocklebur (27.9%), and birch (24.2%). The positivity rate of CCD was 39.4%. Among the samples positive for mugwort, 11 (18.0%), 15 (24.6%), and 15 (24.6%) were positive for Art v 1, Art v 2, and Art v 3, respectively. Among the 67 patients sensitized to ragweed, only five (7.5%) were positive for Amb a 1. In the 40 patients sensitized to birch, Bet v 2 had the highest positivity rate (40.0%). There were 62 patients who were sensitized to walnut. Their components had a lower positivity rate (less than 15%). The hierarchical clustering and optimal scale analysis showed that Art v 4 and Bet v 2 were closely related, and 91.9% of CCD-positive samples were polysensitized. Meanwhile, Spearman's rank correlation method showed that CCD was closely correlated with the sensitization of crude allergen extracts, and there was a low correlation between CCD and allergen components. CCD was highly correlated with goosefoot, ragweed, and walnut trees (r＞0.8). Moreover, there was a strong relationship between the levels of Jug r 3 and Art v 3 (r = 0.78; P < 0.001). CONCLUSIONS: In southern China, the weed pollens (ragweed, cocklebur, and goosefoot) exhibited higher positivity rates in adults and had a stronger relationship with CCD but not with mugwort. The positivity rate of allergen components was not high. CCD-positive samples were always polysensitized.

The effects of loving-kindness and compassion meditation on life satisfaction: A systematic review and meta-analysis.

Loving-kindness and compassion meditation (LKCM) was a promising intervention for improving life satisfaction, but previous findings have been inconsistent. The current study provides a systematic review and meta-analysis, including 23 empirical studies on LKCM with life satisfaction as an outcome variable. The primary meta-analysis indicated that LKCM significantly enhanced life satisfaction in pre-post design (g = 0.312, k = 15, n = 451), but the significance disappeared in the additional meta-analysis based on randomized controlled trials (g = 0.106, k = 6, n = 404). Moderator analyses found significant effects for type of control (i.e., the effects of LKCM were inferior to active control group, but superior to waitlist condition), but not for other moderators (i.e., participant type, previous meditation experience, specific protocol, components of LKCM, combination with mindfulness mediation, and intervention length). Narrative review identified self-compassion and positive emotions as important mediators. The practice time of LKCM had indirect but not direct association with life satisfaction. The findings supported that LKCM is promising in increasing life satisfaction, but more studies are needed to investigate the effects with more rigorous designs. Future studies should investigate other potential mechanisms and clarify whether LKCM change the reality or the perception of life.

Three patterns of sensitization to mugwort, timothy, birch and their major allergen components revealed by Latent class analysis.

BACKGROUND: Mugwort, timothy, and birch are commonly spread pollen allergens across China. Although several studies have described the rates of sensitization to mugwort, timothy, and birch in China, most of them just on specific whole-allergen extracts but little was known about the co-sensitization characteristics of its allergen components. This study aimed to explore the patterns of sensitization to mugwort, timothy, birch, and their major allergen components. METHOD: Serum specific IgE (sIgE) levels of allergen components of mugwort, timothy, birch, and cross-reactive carbohydrate determinants (CCD) were detected in 160 patients whose serum showed positive results to at least one of mugwort, timothy, and birch allergens via EUROBlotMaster system. Skin prick testing was utilized to assess the allergic reaction of grass, weed, and tree allergens. Latent class analysis was used to identify underlying patterns of sensitization to a series of allergen components and their corresponding extracts. RESULTS: 88.8% of patients with allergic rhinitis and/or asthma were positive for mugwort-sIgE, 30% for timothy-sIgE, and 32.5% for birch-sIgE. By using the LCA model, three sensitization patterns as "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized", "Timothy, mugwort, and CCD co-sensitized", "Mugwort and Art v 1 co-sensitized" were revealed based on optimal statistical fit in this study. Compared with other clusters, participants in "Mugwort, Art v 4, Bet v 2 and Phl p 12 co-sensitized" pattern were associated with higher sensitization rates of common grass and tree pollens allergen. The spearman's coefficient between CCD and timothy was larger than the corresponding values of CCD with mugwort or birch. CONCLUSION: CCD and profilin, as minor allergens in pollens, were associated with other pollen sIgE false positives presumably due to cross-reactivity. Patients sensitized with profilin had a significantly higher risk of sensitization to other pollens.

Allergen diagnosis strategy: An experimental application of different methods in Guangzhou, Southern China.

Different methods have different diagnostic value under diverse clinical conditions. This study was conducted to analyze the clinical practical value of different assays in different situations and to establish the concept of an allergen diagnosis strategy.This study used Phadia CAP, Advan Sure (AdvS), Euroline Camera (ELC), and Allergy Lateral Flow Assay (ALFA) kits to detect allergen specific immunoglobulin E (sIgE) in the sera from 30 allergic asthma patients, with Phadia CAP as the gold standard.This study found high sensitivity for Dermatophagoides pteronyssinus in AdvS (92.6%), ELC (88.9%), and ALFA (85.2%), but poor sensitivity for F. domesticus in all three assays. Furthermore, the AdvS, ELC, and ALFA assays could detect 20, 21, and 8 allergens in one panel, respectively. The combination of the results showed that 93.3% and 46.7% of patients tested positive for ≥5 and ≥10 types of allergens, respectively. All patients who were tested positive for the Marine fish mixture were positive for both Shrimp and Crab. Similarly, patients who were tested positive for Chicken also tested positive for Pork. Optimal scale analysis showed a strong connection between Peanut, Soybean, Wheat, Japanese Hop, Western ragweed, and Oak allergens (Cronbach's α = 91.1%).The ELC assay was more suitable for use in pollen-rich areas, whereas the ALFA assay was easy to establish in areas with poor medical conditions. An allergen diagnosis strategy needs to be considered for use in clinical practice.

The Instant Effects of Continuous Transcutaneous Auricular Vagus Nerve Stimulation at Acupoints on the Functional Connectivity of Amygdala in Migraine without Aura: A Preliminary Study.

Background: A growing body of evidence suggests that both auricular acupuncture and transcutaneous auricular vagus nerve stimulation (taVNS) can induce antinociception and relieve symptoms of migraine. However, their instant effects and central treatment mechanism remain unclear. Many studies proved that the amygdalae play a vital role not only in emotion modulation but also in pain processing. In this study, we investigated the modulation effects of continuous taVNS at acupoints on the FC of the bilateral amygdalae in MwoA. Methods: Thirty episodic migraineurs were recruited for the single-blind, crossover functional magnetic resonance imaging (fMRI) study. Each participant attended two kinds of eight-minute stimulations, taVNS and sham-taVNS (staVNS), separated by seven days in random order. Finally, 27 of them were included in the analysis of seed-to-voxel FC with the left/right amygdala as seeds. Results: Compared with staVNS, the FC decreased during taVNS between the left amygdala and left middle frontal gyrus (MFG), left dorsolateral superior frontal gyrus, right supplementary motor area (SMA), bilateral paracentral lobules, bilateral postcingulum gyrus, and right frontal superior medial gyrus, so did the FC of the right amygdala and left MFG. A significant positive correlation was observed between the FC of the left amygdala and right SMA and the frequency/total time of migraine attacks during the preceding four weeks. Conclusion: Continuous taVNS at acupoints can modulate the FC between the bilateral amygdalae and pain-related brain regions in MwoA, involving the limbic system, default mode network, and pain matrix, with obvious differences between the left amygdala and the right amygdala. The taVNS may produce treatment effects by modulating the abnormal FC of the amygdala and pain networks, possibly having the same central mechanism as auricular acupuncture.

Therapeutic potential of adenovirus-encoding brain-derived neurotrophic factor for spina bifida aperta by intra-amniotic delivery in a rat model.

Spina bifida aperta is a type of neural tube defect (NTD). Although prenatal fetal surgery has been an available and effective treatment for it, the neurological functional recovery is still need to be enhanced. Our previous results revealed that deficiencies of sensory, motor, and parasympathetic neurons were primary anomalies that occurred with the spinal malformation. Therefore, we emphasized that nerve regeneration is critical for NTD therapy. We delivered an adenoviral construct containing genes inserted for green fluorescent protein and brain-derived neurotrophic factor (Ad-GFP-BDNF) into the amniotic fluid to investigate its prenatal therapeutic potential for rat fetuses with spina bifida aperta. Using immunofluorescence, TdT-mediated dUTP nick-end labeling staining, and real-time polymerase chain reaction analysis, we assessed cell apoptosis in the defective spinal cord and Brn3a positive neuron survival in the dorsal root ganglion (DRG); a protein array was used to investigate the microenvironmental changes of the amniotic fluid. We found that most of the overexpressed BDNF was present on the lesions of the spina bifida fetuses, the number of apoptosis cells in Ad-GFP-BDNF-transfected spinal cords were reduced, mRNA levels of Bcl2/Bax were upregulated and Casp3 were downregulated compared with the controls, the proportion of Brn3a positive neurons in DRG were increased by activating the BDNF/TrkB/Akt signaling pathway, and most of the significant changes in cytokines in the amniotic fluid were related to the biological processes of regulation of apoptotic process and generation of neurons. These results suggest that intra-amniotic Ad-GFP-BDNF gene delivery might have potential as a supplementary approach to treat congenital malformations of neural tubes.

A pilot study on the allergen-specific IgE to molecular components on polysensitized mite allergic asthmatic patients in Guangzhou, China.

OBJECTIVE: Using multiplex microarray-based component resolved diagnosis (CRD) to investigate the allergen sensitization profile of allergic asthma patients in southern China. METHOD: Serum samples from 57 polysensitized mite allergic asthmatic patients in a tertiary referral centre of southern China were tested with multiplex CRD (ISAC) for specific immunoglobulin E (sIgE) against 112 single allergen and components. Result was then compared with those from singleplex ImmunoCAP. RESULTS: With ISAC, the highest sensitization was seen for nDer f 1 (71.9%), rDer f 2 (73.7%), nDer p 1 (70.2%) and rDer p 2 (66.7%), whereas rDer p 10 and other storage mites' components only showed 10% positivity. rFel d 1 and rCan f 1 were found positive in 29.8% and 14.0% samples respectively. Other epithelia components had less than 7.0% positive rate. Sensitization to pollen components was dominated by nCyn d 1 (17.5%) and nPhl p 4 (12.3%), Carbohydrate cross-reactive determinants (CCD) was positive in 4 patients who were also positive to nPhl p 4, nCyn d 1 and rPla a 2, and all of them have combined asthma and rhinitis. The sensitivity to mold (rAsp f 3), cockroach (nBla g 7) and Anisakis simplex component (rAni s 3) were all the same at 8.8%. 93.0% patients were sensitive to more than one component, with more than half of them (57.9%) positive to five or more components. Patients with combined asthma and rhinitis (AA + AR) were sensitive to more components than those with asthma only (AA). Positive rate to nPhl p 4 was significantly higher in patients with AA + AR than with AA only (χ2 = 4.31, P = 0.038). Compared with ImmunoCAP, ISAC showed a similar high detection rate for D. pteronyssinus and D. farinae, but only 10.0% of B. tropicalis sensitive patients were positive to rBlo t 5. Optimal scale analysis on correlation of allergens components showed rDer p 10 was associated to food allergy. CONCLUSION: Being the first multiplex microarray based CRD study on southern Chinese, ISAC showed house dust mites components were the major allergen components led to sensitization in asthmatic patients. Patients with combined AA + AR were sensitive to more components than those with AA only. Other components with higher positive rate include pollen components nCyn d 1, nPhl P 4 and animal dander components rFel d 1 and rCan f 1. For B. tropicalis, the rBlo t 5 in ISAC may not represent the major Blomia component in southern Chinese patients.

A Component-resolved Diagnostic Approach for a Study on Grass Pollen Allergens in Chinese Southerners with Allergic Rhinitis and/or Asthma.

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen allergens, data on this topic are limited in southern China. Any available data were obtained by self-report questionnaires, skin prick tests, and total or specific IgE tests using crude extracts. For many reasons, these methods are unreliable. Serum sIgE reactivity to Bermuda grass, Timothy grass, and Humulus scandens allergens in a cohort of patients from Greater Guangzhou (southern China's largest city and its outskirts) with allergic rhinitis and/or asthma were examined using a fully-automated immunoassay analyzer as a component-resolved diagnostics (CRD) tool. For the first time, a considerably high prevalence of Bermuda grass sIgE positivity was demonstrated in Chinese southerners with allergic rhinitis and/or asthma. In these patients, a subtle prevalence of sensitization to Timothy grass and Humulus scandens was also noted, which may arise from cross-reactivity, as the latter two are not common in the region. This was also supported by the detection of allergen components. Fully-automated immunoassay analyzers may offer satisfactory consistency between regions, laboratories, and institutions and over time. The automaticity of the instrument may enable a standardized detection that would not have been readily revealed before the advent of CRD. This is a study that uses a CRD approach to investigate sensitization to grass pollen allergens in southern China. It adds to current evidence in the literature. Future studies are needed to validate these findings. However, although CRD is a useful tool, the findings made with the fully-automated immunoassay analyzer should not substitute for other laboratory investigations, clinical evaluations, and physician expertise.

Major grass pollen allergens and components detected in a southern Chinese cohort of patients with allergic rhinitis and/or asthma.

There is so far a paucity of data about allergen component-resolved diagnosis, and the prevalence of grass pollen allergen components in China, in contrast to those from western countries. Even in this country, allergies to grass pollen allergen components in the vast south are inadequately described. This study aimed to determine the major sensitizing grass pollens in Guangzhou, the largest city in Guangdong province of southern China. Included in this study were 258 patients having allergic rhinitis with or without asthma and 88 healthy controls. ImmunoCap100 was used to examine the serum samples for sIgE to Bermuda, Timothy, and Humulus scandens. Subjects who tested positive were further examined for sIgE to Bermuda antigen Cyn d 1, Timothy antigens Phl p 1/4/5/6/7/11/12, and CCD. The relationship of grass pollen allergy to specific antigen sensitization was assessed. As a result, 22.5% of patients with allergic rhinitis and/or asthma were positive for Bermuda-sIgE, 13.6% for Timothy-sIgE, and 7.0% for Humulus scandens-sIgE. These patients were more likely to be sensitized compared with controls (P<0.001). Of the Bermuda-sIgE positive patients, 53.4% were Cyn d 1 positive and 60.3% were Timothy-sIgE positive. Of the Timothy positive patients, 100% were positive for Phl p 4, 17.1% were positive for Phl p 1 and 8.6% tested positive for Phl p 5/6/7/11/12. Patients with high Bermuda-sIgE levels were more likely to be positive for other grasses. In 41.4% of Bermuda grass positive patients, CCD-sIgE was also positive. Sensitization to Phl p 4 was significantly correlated with CCD (rs=0.928).In summary, we found that these southern Chinese patients with allergic rhinitis and/or asthma tested positive for Bermuda, Timothy, and Humulus scandens IgE. A high Bermuda-sIgE level may predict sensitization to other grasses. Correlations between sensitization to CCD and grass pollen allergens suggested a likelihood of cross-reactivity. Further in vitro inhibition assays are required to confirm this relationship.