Possible Mechanism of Sucrose and Trehalose-6-Phosphate in Regulating the Secondary Flower on the Strong Upright Spring Shoots of Blueberry Planted in Greenhouse.

Secondary flowering is the phenomenon in which a tree blooms twice or more times a year. Along with the development of blueberry (Vaccinium corymbosum L.) fruits in spring, a large number of secondary flowers on the strong upright spring shoots were noticed in blueberries planted in the greenhouse. To reveal the cause and possible regulatory mechanism of the phenomenon, we clarified the phenological characteristics of flower bud differentiation and development on the spring shoots by combining phenological phenotype with anatomical observation. Furthermore, the changes in carbohydrates, trehalose-6-phosphate (Tre6P), and the relationship among the key enzyme regulatory genes for Tre6P metabolism and the key regulatory genes for flower formation during the differentiation process of apical buds and axillary buds were investigated. The results showed that the process of flower bud differentiation and flowering of apical and axillary buds was consistent, accompanied by a large amount of carbohydrate consumption. This process was positively correlated with the expression trends of VcTPS1/2, VcSnRK1, VcFT, VcLFY2, VcSPL43, VcAP1, and VcDAM in general, and negatively correlated with that of VcTPP. In addition, there is a certain difference in the differentiation progress of flower buds between the apical and axillary buds. Compared with axillary buds, apical buds had higher contents of sucrose, fructose, glucose, Tre6P, and higher expression levels of VcTPS2, VcFT, VcSPL43, and VcAP1. Moreover, VcTPS1 and VcTPS2 were more closely related to the physiological substances (sucrose and Tre6P) in axillary bud and apical bud differentiation, respectively. It was suggested that sucrose and trehalose-6-phosphate play a crucial role in promoting flower bud differentiation in strong upright spring shoots, and VcTPS1 and VcTPS2 might play a central role in these activities. Our study provided substantial sight for further study on the mechanism of multiple flowering of blueberries and laid a foundation for the regulation and utilization of the phenomenon of multiple flowering in a growing season of perennial woody plants.

Characterization of the MIKCC-type MADS-box gene family in blueberry and its possible mechanism for regulating flowering in response to the chilling requirement.

MAIN CONCLUSION: The expression peak of VcAP1.4, VcAP1.6, VcAP3.1, VcAP3.2, VcAG3, VcFLC2, and VcSVP9 coincided with the endo-dormancy release of flower buds. Additionally, GA4+7 not only increased the expression of these genes but also promoted flower bud endo-dormancy release. The MIKCC-type MADS-box gene family is involved in the regulation of flower development. A total of 109 members of the MIKCC-type MADS-box gene family were identified in blueberry. According to the phylogenetic tree, these 109 MIKCC-type MADS-box proteins were divided into 13 subfamilies, which were distributed across 40 Scaffolds. The results of the conserved motif analysis showed that among 20 motifs, motifs 1, 3, and 9 formed the MADS-box structural domain, while motifs 2, 4, and 6 formed the K-box structural domain. The presence of 66 pairs of fragment duplication events in blueberry suggested that gene duplication events contributed to gene expansion and functional differentiation. Additionally, the presence of cis-acting elements revealed that VcFLC2, VcAG3, and VcSVP9 might have significant roles in the endo-dormancy release of flower buds. Meanwhile, under chilling conditions, VcAP3.1 and VcAG7 might facilitate flower bud dormancy release. VcSEP11 might promote flowering following the release of endo-dormancy, while the elevated expression of VcAP1.7 (DAM) could impede the endo-dormancy release of flower buds. The effect of gibberellin (GA4+7) treatment on the expression pattern of MIKCC-type MADS-box genes revealed that VcAP1.4, VcAP1.6, VcAP3.1, VcAG3, and VcFLC2 might promote flower bud endo-dormancy release, while VcAP3.2, VcSEP11, and VcSVP9 might inhibit its endo-dormancy release. These results indicated that VcAP1.4, VcAP1.6, VcAP1.7 (DAM), VcAP3.1, VcAG3, VcAG7, VcFLC2, and VcSVP9 could be selected as key regulatory promoting genes for controlling the endo-dormancy of blueberry flower buds.

New Strategy for Improvement of Interfacial Interactions between Poly(arylene sulfide sulfone) and Carbon Fiber by Grafting Polymeric Chains via Thiol-Ene Click Chemistry.

A simple and efficient strategy for enhancing the interfacial interaction in carbon fiber-reinforced poly(arylene sulfide sulfone) (CF/PASS) composites by grafting polymeric chains via thiol-ene click chemistry is reported here. Simultaneously, three thiol compounds and carbon nanotubes were grafted on CFs to explore the reaction between the CF and thiol groups. X-ray photoelectron spectroscopy, Raman spectroscopy, and normalized temperature-dependent IR spectroscopy results confirm the successful grafting of three thiol compounds, carbon nanotubes, and polymer chains. Similarly, obvious changes on the CF surface can be seen before and after modification via scanning electron microscopy, such as grafted nanotubes and polymeric resin, and the increase in the modulus gradient and interfacial thickness of CF/PASS can be clearly seen via atomic force microscopy. All the results of micro and macro tests on mechanical properties indicate that connecting low molecular weight thiol-terminated PASS (HS-LPASS) onto CFs enhances the interfacial property and mechanical performance of CF/PASS to a greater extent. The interfacial shear strength, interlaminar shear strength, and tensile strength of CF@HS-LPASS-reinforced PASS (CF@HS-LPASS/PASS) increase significantly by 38.5, 43.6, and 24.4%, respectively. All the results demonstrate that thiol-ene click reactions can be used for CF modification; furthermore, in the presence of external stress, the grafted polymeric interphase can act as a "bridge layer" to improve the stress transfer efficiency.

Home-based Vestibular Rehabilitation: A Feasible and Effective Therapy for Persistent Postural Perceptual Dizziness (A Pilot Study).

INTRODUCTION: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder where there is persistent dizziness or unsteadiness occurring on most days for more than 3 months duration. Treatment recommendations for PPPD include vestibular rehabilitation therapy (VRT) with or without medications and/or cognitive behavioral therapy. OBJECTIVES: This paper is a pilot study designed to compare the effects of Bal Ex as a home-based VRT on the quality of life (EQ-5D), dizziness handicap (DHI) and mental health (DASS-21) against hospital-based VRT. DESIGN: This was an assessor-blinded, randomized controlled pilot study where PPPD patients were randomly selected to undergo Bal Ex, the home-based VRT (intervention group) or hospital-based (control group) VRT. The participants were reviewed at 4 weeks and 12 weeks after the start of therapy to assess the primary endpoints using the subjective improvement in symptoms as reported by patients, changes in DHI scores, DASS-21 scores and EQ5D VAS scores. RESULTS: Thirty PPPD patients successfully completed the study with 15 in each study group. Within 4 weeks, there were significant improvements in the total DHI scores as well as anxiety levels. By the end of 12 weeks, there were significant improvements in the DHI, DASS-21 and EQ5D. The degree of improvement between Bal Ex and the control was comparable. CONCLUSION: VRT is an effective modality in significantly improving quality of life, dizziness handicap, depression, and anxiety levels within 3 months in PPPD. Preliminary results show Bal Ex is as effective as hospital-based VRT and should be considered as a treatment option for PPPD.

Improve the Interfacial Properties between Poly(arylene sulfide sulfone) and Carbon Fiber by Double Polymeric Grafted Layers Designed on a Carbon Fiber Surface.

Double polymeric grafted layer is constructed by two steps of chemical reaction, in which two polymers had been used, respectively polydopamine (PDA) film and modified PASS (NH2-PASS) resin containing amine group, as the interphase in carbon fiber reinforced poly(arylene sulfide sulfone) (PASS) composite (CF/PASS) to work on enhancing the interfacial property. All the test results of chemical components and chemical structures on the carbon fiber surface show that the double polymeric grafted layer was constructed successfully with PDA and NH2-PASS chains. And obvious characteristics of thin PDA film and a polymer layer can be clearly seen in the morphology of modified carbon fiber. In addition to this, the obvious interphase and change in the thickness of interphase have been observed in the modulus distribution images of CF/PASS. The final superb performance is achieved by PASS composites with a double polymeric grafted layer, 27.2% and 198.6% superior to the original PASS composite for IFSS and ILSS, respectively. Moreover, the result also indicates that constructing a double polymeric grafted layer on a carbon fiber surface is a promising technique to modify carbon fiber for processing high-performance advanced thermoplastic composites and is more environmental friendly as well as convenient.

Neuroimaging Systematic Review in Persistent Postural-Perceptual Dizziness: The Elaborate Alterations in the Delicate Network to Remain Balanced.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder that may have normal physical examination, clinical laboratory testing and vestibular evaluation. However, advances in neuroimaging have provided new insights in brain functional connectivity and structure in patients with PPPD. This systematic review was aimed at identifying significant structural or alterations in functional connectivity in patients with PPPD. DATABASES REVIEWED: Science Direct, Pubmed, Embase via Ovid databases, and Cochrane library. METHODS: This review following the guidelines of PRISMA, systematically and independently examined papers published up to March 2021 which fulfilled the predetermined criteria. PROSPERO Registration (CRD42020222334). RESULTS: A total of 15 studies were included (MRI = 4, SPECT = 1, resting state fMRI = 4, task-based fMRI = 5, task-based fMRI + MRI = 1). Significant changes in the gray matter volume, cortical folding, blood flow, and connectivity were seen at different brain regions involved in vestibular, visual, emotion, and motor processing. CONCLUSION: There is a multisensory dimension to the impairment resulting in chronic compensatory changes in PPPD that is evident by the significant alterations in multiple networks involved in maintaining balance. These changes observed offer some explanation for the symptoms that a PPPD patient may experience.Systematic Review Registration: This study is registered with PROSPERO (CRD42020222334).

The impact of disease duration in persistent postural-perceptual dizziness (PPPD) on the quality of life, dizziness handicap and mental health.

BACKGROUND: Persistent Postural-Perceptual Dizziness (PPPD) is a chronic functional disorder which interferes with the way individuals experience their personal, social and work life. OBJECTIVE: To study the impact of disease duration in PPPD on the quality of life (QOL), dizziness handicap and mental health on the patients. METHODS: A prospective study comparing the EQ-5D for QOL, Dizziness Handicap Inventory (DHI) and DASS-21 between 27 patients with PPPD and 27 of those who have recovered from an acute vestibular event. Similar parameters between PPPD patients with symptoms less than one year and more than a year were compared. RESULTS: The PPPD patients were predominantly females and middle-aged with significantly higher DHI scores (mean 48.3 + 25.7, p = 0.00002), higher total mean scores in the DASS-21 (mean 21.6 + 13.7, p = 0.009) and poorer QOL with mean EQ-5D VAS of 67.9 + 17.3 (p < 0.00001). PPPD patients with symptoms for more than a year had significant increase in physical handicap (p = 0.041) as well as anxiety levels (p = 0.008). CONCLUSIONS: PPPD is predominantly seen in females and middle-aged which significantly reduces the QOL, increases dizziness handicap and increases depression, anxiety and stress levels. The increase in duration of illness further increases the anxiety levels and physical handicap.

Vascular Loops: The Innocent Bystander for Vestibular Paroxysmia.

INTRODUCTION: Vestibular paroxysmia (VP) is a condition with recurrent short bouts of vertigo and is thought to be part of a neurovascular compression syndrome caused by the vascular loop. However, this is still being debated as vascular loops are considered as normal variants with limited studies involving vertiginous patients. OBJECTIVES: The aim of this paper is to study the association between audiovestibular symptoms and the presence of vascular loops and to study the association between vestibular paroxysmia and vascular loops. DESIGN: This is a retrospective analysis of clinical, audiological and MRI findings of patients with and without vascular loops and vestibular paroxysmia from 2000 to 2020. RESULTS: A total of 470 MRI Internal Auditory Meatus scans were performed during the study period of which, 71 (15.1%) had vascular loops and 162 (34.5%) had normal MRI which were used as controls. From the 233 subjects recruited, there were 37 subjects with VP and 196 non VP subjects were used as controls. There was no association between the vascular loop and control groups in terms of co-morbidity and audiovestibular symptoms. The VP group had a significantly older mean age of 51.8 (SD ± 10.3) as compared to the non VP group with the mean age of 45.6 (SD ± 15.5). The VP group had higher number of patients presenting with hearing loss at 97.3% when compared with those without VP (80.1%) (P = .01). The odds of having a vascular loop giving rise to VP was not statistically significant at 0.82 (95% CI 0.3735-1.7989) P = .62. CONCLUSION: The vascular loop is a normal variant which may or may not give rise to audiovestibular symptoms or vestibular paroxysmia. Clinical assessment is still most important tool in deriving a diagnosis of VP and MRI may be useful to rule out other central causes.

Cord blood soluble Fas ligand linked to allergic rhinitis and lung function in seven-year-old children.

BACKGROUND: Serum or cord blood soluble Fas ligand (FasL) has been related to asthma, allergic rhinitis, and atopic dermatitis in cross-sectional and short-term follow-up studies. However, the association of cord blood soluble FasL with long-term allergic outcomes has seldom been investigated. METHODS: The Prediction of Allergies in Taiwanese Children birth cohort study recruited healthy newborns upon delivery. At birth, blood was collected from the umbilical cords of these children, and the cord blood soluble Fas ligand levels were measured. At the age of seven years, the allergic outcome of each child was diagnosed by pediatric allergists and pulmonologists. Tests were conducted to measure the specific immunoglobulin E, fractional exhaled nitric oxide (FeNO), and pulmonary function levels of each child. RESULTS: Cord blood soluble FasL levels were higher in seven-year-old children with allergic rhinitis (Odds ratio [OR] = 2.41, p = 0.012) and expiratory airway obstruction (the highest forced expiratory volume in 1 second/forced vital capacity < 90%, OR = 2.11, p = 0.022). The FeNO and Dermatophagoides pteronyssinus-specific immunoglobulin E levels of seven-year-old children were positively correlated with cord blood soluble FasL levels (p = 0.006 and 0.02, respectively). CONCLUSION: In this birth cohort, the cord blood soluble FasL levels were associated with allergic rhinitis, obstructive-type lung function, FeNO, and house dust mite sensitization in 7-year-old children. The cord blood soluble FasL level might be used as a predictor for allergic diseases in children who are 7 years old.

Can Priming Multiple Identities Enhance Divergent Thinking for Middle School Students?

Previous studies have found that promoting multiple identities can improve children's creative performance (divergent thinking). The present study employed a priming paradigm to design two experiments and investigate whether promoting a sense of multiple identities in middle school students could enhance their divergent thinking, a key component of creativity. In Experiment 1, 77 junior high school students were divided into multiple identities and physical trait condition groups. They were instructed to think about a child with multiple identities or physical traits. The results showed that there were no differences in divergent thinking (DT) scores between the two groups. In Experiment 2, we modified the priming method by asking participants to think about and write a description of the various identities or physical traits and employed a subjective top-scoring method to make up for shortcomings in the traditional scoring method when applied to originality. The results still showed no significant difference in scores between the identity and physical trait groups. Thus, the results of this study contradict those of previous research, which found that the identity group demonstrated significantly higher scores on a creativity test than did those in the physical trait group. Several potential factors affect this outcome, but it seems that priming to enhance divergent thinking is not particularly effective. Thus, the social priming effect should be pursued with caution regarding both replicability and generalizability.

Biological effects and mechanisms of matrine and other constituents of Sophora flavescens in colorectal cancer.

The plant Sophora flavescens Ait. has been used in the clinical management of colorectal cancer (CRC). Its constituent compounds, notably the alkaloids matrine, oxymatrine, and sophoridine, have received considerable research attention in experimental models of CRC in vivo and in vitro. This review found that extracts of S. flavescens and/or its constituent compounds have been reported to inhibit CRC cell proliferation by inducing cell-cycle arrest at the G1 phase, inducing apoptosis via the intrinsic pathway, interfering in cancer metabolism, inhibiting metastasis and angiogenesis, regulating senescence and telomeres, regulating the tumour microenvironment and down-regulating cancer-related inflammation. In addition, matrine and oxymatrine reversed multi-drug resistance and enhanced the effects of chemotherapies. These anti-cancer effects were associated with regulation of several cellular signalling pathways including: MAPK/ERK, PI3K/AKT/mTOR, p38MAPK, NF-κB, Hippo/LATS2, TGF-ß/Smad, JAK/STAT3, RhoA/ROC, and Wnt/ ß-catenin pathways. These multiple actions in CRC suggest the alkaloids of S. flavescens may be therapeutic candidates for CRC management. Nevertheless, there remains considerable scope for future research into its flavonoid constituents, the effects of combinations of compounds, and the interaction between these compounds and anti-cancer drugs. In addition, more research is needed to investigate likely drug ligand-receptor interactions for each of the bioactive compounds.

The Synergistic Antitumor Effect of Tanshinone IIA Plus Adriamycin on Human Hepatocellular Carcinoma Xenograft in BALB/C Nude Mice and Their Influences on Cytochrome P450 CYP3A4 In Vivo.

OBJECTIVE: Hepatocellular carcinoma is one of the most common diseases that seriously threaten human life and health. In this study, we evaluated the inhibitory effect of tanshinone IIA (Tan IIA) combined with adriamycin (ADM) on human hepatocellular carcinoma and developed a platform to assess the function if Chinese herbal ingredients combined with chemotherapy drugs have synergistic antitumor effects in vivo. METHODS: Established animal model of human hepatocarcinoma HepG2 cell in nude mice. Mice were divided into model control group, Tan IIA group, ADM group, and Tan IIA + ADM group. The changes from general condition, weight, tumor volume, and inhibition rate were observed. The data were gathered from serum AST level and histopathological changes. The content and activity of cytochrome P450 were determined by spectrophotometric analysis. CYP3A4 protein expression was analyzed by western blotting. The binding model crystal structure of Tan IIA and ADM with pregnane X receptor (PXR) was evaluated by Discovery Studio 2.1. RESULTS: A combination of Tan IIA with ADM could improve life quality by relieving ADM toxicity, decreasing tumor volume, declining serum AST level, and improving liner pathological section in tumor-bearing mice. The inhibitory rates of Tan IIA, ADM, and cotreatment were 32.77%, 60.96%, and 73.18%, respectively. The Tan IIA group significantly enhanced the content of cytochrome b5, P450, and erythromycin-N-demethylase activity. CYP3A4 protein expression was enhanced obviously by the Tan IIA + ADM group. Virtual molecular docking showed that both Tan IIA and ADM could be stably docked with the same binding site of PXR but different interactions. CONCLUSIONS: Tan IIA in combination with ADM could improve the life quality in tumor-bearing mice and enhance the antitumor effect. The Tan IIA group increased the concentration of cytochrome P450 enzymes and activity. Combined Tan IIA with ADM could upregulate the CYP3A4 protein expression and make relevant interaction with protein PXR by virtual docking.

Percutaneous Full-Endoscopic Lumbar Foraminoplasty and Decompression by Using a Visualization Reamer for Lumbar Lateral Recess and Foraminal Stenosis in Elderly Patients.

BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.

Asymptomatic toddlers with house dust mite sensitization at risk of asthma and abnormal lung functions at age 7 years.

OBJECTIVE: To evaluate the predictive value of asymptomatic early house dust mite sensitization on allergic outcomes and pulmonary functions in 7-year olds. STUDY DESIGN: The Prediction of Allergies in Taiwanese Children (PATCH) birth cohort study recruited healthy newborns at birth. At age 1.5-2 years, a Dermatophagoides pteronyssinus-specific immunoglobulin E level ≥ 0.35 kU/L was defined as early sensitization. At age 7 years, allergic outcomes were evaluated by pediatric allergists and pulmonologists, and fractional exhaled nitric oxide and pulmonary functions were measured. RESULTS: At age 1.5-2 years, 28.0% of toddlers were sensitized to D. pteronyssinus. Among them, 68.2% had no allergic symptoms at that time. At age 7 years, the children with early sensitization had higher risks of asthma (OR = 13.4, 95% CI, 1.2 to 153.0; P = 0.037), allergic rhinitis (OR = 10.2, 95% CI, 2.1 to 49.6; P = 0.004), and atopic dermatitis (OR = 38.5, 95% CI, 2.1 to 696.4; P = 0.014). Notably, even the asymptomatic toddlers with early D. pteronyssinus sensitization had higher probabilities of asthma (12.5% vs. 1.7%, P = 0.040), allergic rhinitis (83.3% vs. 43.1%, P = 0.009), and atopic dermatitis (20.8% vs. 0.0%, P < 0.001) at age 7 years. The asymptomatic toddlers with early sensitization also had higher exhaled nitric oxide levels and higher prevalence of airway hyperresponsiveness at age 7 years. CONCLUSION: Asymptomatic toddlers with early house dust mite sensitization have higher risks of developing asthma, allergic rhinitis, atopic dermatitis, and abnormal lung functions at age 7 years.

Urotensin II: an inflammatory cytokine.

Urotensin II (UII) is a polypeptide molecule with neurohormone-like activity. It has been confirmed that UII is widely distributed in numerous organs of different animal species from fish to mammals, including humans. The UII receptor is orphan G-protein coupled receptor 14, also known as UT. The tissue distribution of UII and UT is highly consistent, and their expression may be regulated by autocrine and paracrine mechanisms. In the body, UII has many physiological and pathophysiological activities, such as vasoconstrictor and vasodilatory actions, cell proliferation, pro-fibrosis, neuroendocrine activity, insulin resistance, and carcinogenic and inflammatory effects, which have been recognized only in recent years. In fact, UII is involved in the process of inflammatory injury and plays a key role in the onset and development of inflammatory diseases. In this paper, we will review the roles UII plays in inflammatory diseases.

Matrine induces apoptosis in multiple colorectal cancer cell lines in vitro and inhibits tumour growth with minimum side effects in vivo via Bcl-2 and caspase-3.

BACKGROUND: The World Health Organization (WHO) reported that colorectal cancer (CRC) was the third most common cancer in men and the second in women, worldwide. Our previous meta-analysis found Sophora flavescens increased tumour response rate in randomised controlled trials of CRC. We hypothesised that its principal constituent matrine had exerted anti-tumour effects. PURPOSE: To elucidate its mechanisms of action we investigated the dose-related anti-tumour effects of matrine on four human CRC cell-lines: LS174T, Caco-2, SW1116 and RKO. In a LS174T xenografted tumour model in nude mice we assessed the effects of matrine and oxaliplatin on tumour volume, weight and morphology. Computer simulated dockings for target proteins were also conducted. METHODS AND DESIGN: Cell viability, cell cycle and apoptosis were measured by Cell Counting Kit-8 and flow cytometry, and Annexin V-FITC/PI double staining assay respectively. Western blot was performed to examine the expression of Bax, Bcl-2 and caspase-3 in the cells. The xenograft model and immunohistochemistry were used to investigate the effect of matrine in vivo. Oxaliplatin was set as positive control. Molecular docking was performed to predict the binding modes of matrine and oxaliplatin with target proteins using CDOCKER algorithm. RESULTS: Matrine inhibited proliferation of cancer cells in a dose- and time-dependent manner. Matrine induced cell-cycle arrest at G1/G0 phase, induced apoptosis and reduced expression of Bcl-2 and caspase-3 while up-regulating Bax and cleaved caspase-3 in the four CRC cells. In vivo, matrine significantly inhibited tumour growth without side effects on physical health compared to the negative (vehicle) control group. Mice in the oxaliplatin group lost vigour, became frail and lost weight. Expression of Bcl-2 in tumour tissue was lower and Bax expression was higher in the matrine-treated groups compared to the negative control. In computer-simulated docking, matrine successfully docked into active sites of Bcl-2 and caspase-3. CONCLUSION: Matrine inhibited growth of colorectal cancer cells in vitro and in vivo. A molecular mechanism was apoptosis induction via effects on Bcl-2, Bax and caspase-3. Moreover, matrine showed minimum side effects and may provide a candidate for the development of new therapies for colorectal cancer.

Matrine combined with cisplatin synergistically inhibited urothelial bladder cancer cells via down-regulating VEGF/PI3K/Akt signaling pathway.

BACKGROUND: Cisplatin is one of the first-line drugs for urothelial bladder cancer (UBC) treatment. However, its considerable side effects and the emergence of drug resistance are becoming major limitations for its application. This study aimed to investigate whether matrine and cisplatin could present a synergistic anti-tumor effect on UBC cells. METHODS: Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of the UBC cells. Wound healing assay and transwell assay were applied respectively to determine the migration and invasion ability of the cells. The distribution of cell cycles, the generation of reactive oxygen species (ROS) and the apoptosis rate were detected by flow cytometry (FCM). The expressions of the relative proteins in apoptotic signal pathways and the epithelial-mesenchymal transition (EMT) related genes were surveyed by western blotting. The binding modes of the drugs within the proteins were detected by CDOCKER module in DS 2.5. RESULTS: Both matrine and cisplatin could inhibit the growth of the UBC cells in a time- and dose-dependent manner. When matrine combined with cisplatin at the ratio of 2000:1, they presented a synergistic inhibitory effect on the UBC cells. The combinative treatment could impair cell migration and invasion ability, arrest cell cycle in the G1 and S phases, increase the level of ROS, and induce apoptosis in EJ and T24 cells in a synergistic way. In all the treated groups, the expressions of E-cadherin, ß-catenin, Bax, and Cleaved Caspase-3 were up-regulated, while the expressions of Fibronectin, Vimentin, Bcl-2, Caspase-3, p-Akt, p-PI3K, VEGFR2, and VEGF proteins were down-regulated, and among them, the combination of matrine and cisplatin showed the most significant difference. Molecular docking algorithms predicted that matrine and cisplatin could be docked into the same active sites and interact with different residues within the tested proteins. CONCLUSIONS: Our results suggested that the combination of matrine and cisplatin could synergistically inhibit the UBC cells' proliferation through down-regulating VEGF/PI3K/Akt signaling pathway, indicating that matrine may serve as a new option in the combinative therapy in the treatment of UBC.

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way.

BACKGROUND: The study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers. METHODS: Inhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins. RESULTS: Both tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin. CONCLUSIONS: Tanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.

Cord Blood Soluble CD14 Predicts Wheeze and Prolonged Cough in Young Children: The PATCH Study.

BACKGROUND: Soluble cluster of differentiation 14 (sCD14) plays a role in the development and manifestation of atopic symptoms, although the results of previous studies have been inconclusive. The aim of this study is to evaluate the practical use of sCD14 as a predictive biomarker of allergy in young children. METHODS: Children aged 0-1 year from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Cord blood sCD14 concentrations were measured. Pediatrician evaluation and questionnaire interviews were performed periodically until 1 year of age to determine the children's allergic and respiratory symptoms. RESULTS: Two hundred and six 1-year-old subjects were enrolled. Wheeze was positively associated with cord blood sCD14, a family member with asthma and parental smoking. Prolonged cough was associated with cord blood sCD14, older maternal age and more siblings. In the multivariate logistic regression analysis, cord blood sCD14 was the only independent predictive biomarker for wheeze and prolonged cough by 1 year of age. Every 100-ng/ml increase in cord blood sCD14 resulted in a 1.56-fold higher risk of developing wheeze and a 1.62-fold higher risk of prolonged cough in children by 1 year of age. CONCLUSIONS: Cord blood sCD14 may be a useful biomarker for predicting infant wheeze and prolonged cough by 1 year of age.