Carboxymethyl potato starch hydrogels encapsulated cyclodextrin metal-organic frameworks for enantioselective loading of S-naproxen and its programmed release.

A natural polysaccharide-based vehicle is facilely prepared for enantioselective loading of S-naproxen (S-NPX) and its programmed release. Cyclodextrin metal-organic frameworks (CD-MOF) are synthesized through the coordination of K+ with γ-cyclodextrin (γ-CD). Compared with R-NPX, the CD-MOF preferably combines with S-NPX, which can be confirmed by the thermodynamic calculations. The S-NPX loaded CD-MOF (CD-MOF-S-NPX) is grafted with disulfide bond (-S-S-) to improve its hydrophobicity, and the loaded S-NPX is further encapsulated in the chiral cavity of γ-CD by carboxymethyl potato starch (CPS) hydrogels. The intermolecular hydrogen bonding of the CPS hydrogels is prone to be destroyed in mildly basic media (∼pH 8.0), resulting in the swelling of the hydrogels; the -S-S- linkage in the vehicle can be cleaved in the presence of glutathione (GSH), leading to the collapse of the CD-MOF. Therefore, the programmed release of S-NPX can be achieved. Also in this work, the release kinetics is investigated, and the results indicate that the release of S-NPX is controlled by the Higuchi model.

Arginyl-fructosyl-glucose from red ginseng alleviates TGF-ß1-induced epithelial-mesenchymal transition of renal tubular epithelial cells.

This study aims to explore the effect and mechanism of arginyl-fructosyl-glucose (AFG) on TGF-ß1-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. HK-2 cells were induced by TGF-ß1 and then co-cultured with AFG at different concentrations (0, 25, 50, and 100 µmol/l) for 48 h. The morphology of HK-2 cells was observed under an inverted microscope and the expressions of α-SMA, Vimentin, and E-cadherin were assessed by qRT-PCR, Western blot, and immunofluorescence. The mRNA expressions of ERK and STAT3 were also examined by qRT-PCR, and the protein levels of ERK, STAT3, p-ERK, and p-STAT3 were measured by Western blot. Finally, CCK-8 and transwell assays were used to detect cell proliferation and invasion. TGF-ß1 treatment significantly induced EMT in HK-2 cells. The expressions of p-ERK and p-STAT3 were signally increased after TGF-ß1 induction, while Mogrol treatment inhibited p-ERK, p-STAT3, α-SMA, and Vimentin expression levels, enhanced E-cadherin expression, and suppressed cell proliferation and invasion. AFG exposure could also inhibit p-ERK, p-STAT3, α-SMA, and Vimentin expressions, promote E-cadherin expression, and markedly inhibit HK-2 cell proliferation and invasion. AFG inhibited TGF-ß1-induced EMT of renal tubular epithelial cells by regulating phosphorylation of ERK and STAT3.

Aromatherapy with inhalation effectively alleviates the test anxiety of college students: A meta-analysis.

Objective: Test anxiety is one of the common psychological and behavioral problems of college students, which can result in poor academic performance and even academic failure. Aromatherapy has been proposed as a promising method to reduce test anxiety in college students, but its precise efficacy has not been fully confirmed. This meta-analysis evaluated the effects of aromatherapy on the symptoms of test anxiety in college students to serve as a reference for future research and provide more scientific and exact evidence. Methods: PubMed, The Cochrane Library, Web of Science, Embase, CINAHL, Science Direct, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Full-Text Database (VIP), and Wanfang Data were electronically searched from inception to June 2022 to identify randomized controlled trials (RCTs) on aromatherapy for treating students' test anxiety. The Cochrane Risk of Bias Assessment Tool for RCTs was used by two reviewers to critically and independently assess the methodological quality of the included studies. Review Manager 5.4 was used for the meta-analysis. Stata 17.0 was used for sensitivity analysis and Egger's test. Results: Seven RCTs included 425 patients, with a moderate risk of bias in the included studies. The meta-analysis found that aromatherapy effectively reduced test anxiety in college students (SMD = -0.67, p < 0.01), with high heterogeneity of results (I 2 = 72%). The different types of essential oil devices used in the study are the source of inter-study heterogeneity. Subgroup analysis suggested that most effective methods were aromatherapy with compound essential oils (SMD = -0.91, p < 0.01), and using cloths or pads as the essential oil devices (SMD = -1.03, p < 0.01). There was no difference between aromatherapy and placebo control groups (SMD = -0.65, p = 0.25). Conclusion: Aromatherapy with inhalation can help relieve test anxiety in college students, but more and higher-quality studies are needed. This study provides a reference for future research designs in terms of the selection of essential oil types and devices and the design of research groups. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022345767].

Evaluation of adalimumab biosimilar candidate (HS016) in Chinese patients with active ankylosing spondylitis based on a health survey: sub-analysis of a phase 3 study.

OBJECTIVE: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. METHODS: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. RESULTS: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. CONCLUSION: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. TRIAL REGISTRATION: http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.

The natural product berberine synergizes with osimertinib preferentially against MET-amplified osimertinib-resistant lung cancer via direct MET inhibition.

Berberine is a natural product that has long been used in traditional Chinese medicine due to its antimicrobial, anti-inflammatory and metabolism-regulatory properties. Osimertinib is the first third-generation EGFR-tyrosine kinase inhibitor (TKI) approved for the treatment of non-small cell lung cancer (NSCLC) with activating EGFR mutations and those resistant to earlier generation EGFR-TKIs due to a T790M mutation. However, emergence of acquired resistance to osimertinib limits its long-term efficacy in the clinic. One known mechanism of acquired resistance to osimertinib and other EGFR-TKIs is MET (c-MET) gene amplification. Here, we report that berberine, when combined with osimertinib, synergistically and selectively decreased the survival of several MET-amplified osimertinib-resistant EGFR mutant NSCLC cell lines with enhanced induction of apoptosis likely through Bim elevation and Mcl-1 reduction. Importantly, this combination effectively enhanced suppressive effect on the growth of MET-amplified osimertinib-resistant xenografts in nude mice and was well tolerated. Molecular modeling showed that berberine was able to bind to the kinase domain of non-phosphorylated MET, occupy the front of the binding pocket, and interact with the activation loop, in a similar way as other known MET inhibitors do. MET kinase assay showed clear concentration-dependent inhibitory effects of berberine against MET activity, confirming its kinase inhibitory activity. These findings collectively suggest that berberine can act as a naturally-existing MET inhibitor to synergize with osimertinib in overcoming osimertinib acquired resistance caused by MET amplification.

Enhancement of carotenoid production and its regulation in edible mushroom Cordyceps militaris by abiotic stresses.

Cordyceps militaris carotenoids are widely used as food additives, animal feed supplements, and so on. However, the biosynthetic pathway of carotenoids in C. militaris is still obscure. In this paper, changes of mycelial morphology and carotenoid accumulation of C. militaris were investigated under oxidative (KMnO4) and osmotic stress (NaCl). Subsequently, qRT-PCR was employed to detect the expression levels of genes related to carotenogenesis to explore the mechanism of adaptation to abiotic stress. When the concentrations of KMnO4 and NaCl were respectively 0.4 g/L and 2 g/L, carotenoid accumulation reached a maximum of 6616.82 ±â€¯666.43 µg/g and 6416.77 ±â€¯537.02 µg/g. Under the oxidative stress condition of KMnO4, the expressions of psy and hsp70 increased significantly compared with control. Besides, the genes fus3 and hog1 were significantly enriched in the MAPK signal pathway. Compared with the control group, there was no significant difference in expression of psy in the NaCl group. Moreover, the accumulation of triacylglycerols may contribute significantly to the increase in carotenoid accumulation. The increased accumulation of antioxidant carotenoids induced under environmental stress is to resist oxidative conditions. Fus3 and Hog1 signaling in the MAPK pathway was activated and subsequently take effects on the resistance of oxidative condition by regulating related metabolic processes. C. militaris resist the stress of high oxygen by producing a large amount of glycerol and carotenoids when this fungus is cultured in a saline environment for a long time.

Discovery of Novel Substituted N-(4-Amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide Analogues as Potent Human Adenovirus Inhibitors.

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds 6 and 43 possibly target the HAdV DNA replication process, while compounds 46 and 47 suppress later steps of HAdV life cycle. Notably, among these derivatives, compound 15 showed improved anti-HAdV activity (IC50 = 0.27 µM), significantly decreased cytotoxicity (CC50 = 156.8 µM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections.

Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation.

Bromodomain-containing protein 4 (BRD4) represents a promising drug target for anti-inflammatory therapeutics. Herein, we report the design, synthesis, and pharmacological evaluation of novel chromone derivatives via scaffold hopping to discover a new class of orally bioavailable BRD4-selective inhibitors. Two potent BRD4 bromodomain 1 (BD1)-selective inhibitors 44 (ZL0513) and 45 (ZL0516) have been discovered with high binding affinity (IC50 values of 67-84 nM) and good selectivity over other BRD family proteins and distant BD-containing proteins. Both compounds significantly inhibited the expression of Toll-like receptor-induced inflammatory genes in vitro and airway inflammation in murine models. The cocrystal structure of 45 in complex with human BRD4 BD1 at a high resolution of 2.0 Å has been solved, offering a solid structural basis for its binding validation and further structure-based optimization. These BRD4 BD1 inhibitors demonstrated impressive in vivo efficacy and overall promising pharmacokinetic properties, indicating their therapeutic potential for the treatment of inflammatory diseases.

Synthesis and Biochemical Evaluation of Noncyclic Nucleotide Exchange Proteins Directly Activated by cAMP 1 (EPAC1) Regulators.

Exchange proteins directly activated by cAMP (EPAC) play a central role in various biological functions, and activation of the EPAC1 protein has shown potential benefits for the treatment of various human diseases. Herein, we report the synthesis and biochemical evaluation of a series of noncyclic nucleotide EPAC1 activators. Several potent EPAC1 binders were identified including 25g, 25q, 25n, 25u, 25e, and 25f, which promote EPAC1 guanine nucleotide exchange factor activity in vitro. These agonists can also activate EPAC1 protein in cells, where they exhibit excellent selectivity toward EPAC over protein kinase A and G protein-coupled receptors. Moreover, 25e, 25f, 25n, and 25u exhibited improved selectivity toward activation of EPAC1 over EPAC2 in cells. Of these, 25u was found to robustly inhibit IL-6-activated signal transducer and activator of transcription 3 (STAT3) and subsequent induction of the pro-inflammatory vascular cell adhesion molecule 1 (VCAM1) cell-adhesion protein. These novel EPAC1 activators may therefore act as useful pharmacological tools for elucidation of EPAC function and promising drug leads for the treatment of relevant human diseases.

Comparison of different calcium supplementation methods in patients with osteoporosis.

The aim of the present study was to explore the clinical efficacy and safety of different methods of calcium supplementation in osteoporosis (OP). Patients with OP were divided into four groups, including the control, oral calcium supplementation, intravenous calcium supplementation and combined calcium supplementation groups. The duration of the calcium supplementation was 3-6 years. Medical records were collected and examined along with demographic data, the incidence of certain diseases and adverse reactions. All subjects in the three treatment groups exhibited statistically significant reductions in alkaline phosphatase (ALP) levels, visual analog score (VAS) and Oswestry Disability Index (ODI) compared with the respective pre-treatment values. Furthermore, compared with prior to treatment, the lumbar and hip bone mineral density (BMD) of patients receiving intravenous calcium supplementation was significantly increased. In addition, after treatment, the lumbar and hip BMD was significantly increased, whereas ALP levels, VAS and ODI were significantly decreased in the oral calcium supplementation group compared with the control group. Also, compared with the control and oral calcium supplementation groups, the BMD was significantly increased, whereas ALP, VAS, ODI, the rate of infection and tooth loss, the incidence of fragility fractures, joint replacement surgery, arrhythmia, lumbar disc herniation and cerebral infarction were significantly decreased in the two groups treated with intravenous calcium supplementation. The results of the present study may enable a better understanding of the effectiveness and safety of the different methods for supplementing calcium in OP.

Design, Synthesis, and Biological Evaluation of Substituted 4,6-Dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione Analogues as Potent NS4B Inhibitors for the Treatment of Dengue Virus Infection.

A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5-b]pyridine-7,3'-indoline]-2',5(3H)-dione analogues were synthesized and evaluated as potent dengue virus inhibitors. Throughout a structure-activity relationship exploration on the amide of the indolone moiety, a wide range of substitutions were found to be well tolerated for chemical optimization at this position. Among these compounds, 15 (JMX0254) displayed the most potent and broad inhibitory activities, effective against DENV-1 to -3 with EC50 values of 0.78, 0.16, and 0.035 µM, respectively, while compounds 16, 21, 27-29, 47, and 70 exhibited relatively moderate to high activities with low micromolar to nanomolar potency against all four serotypes. The biotinylated compound 73 enriched NS4B protein from cell lysates in pull-down studies, and the findings together with the mutation investigations further validated dengue NS4B protein as the target of this class of compounds. More importantly, compound 15 exhibited good in vivo pharmacokinetic properties and efficacy in the A129 mouse model, indicating its therapeutic potential against the dengue virus infection as a drug candidate for further preclinical development.

Conventional and Complementary Therapy Use among Mexican Farmworkers in North Carolina: Applying the I-CAM-Q.

Objectives: This analysis documents the use of conventional health-care providers, traditional healers, and complementary therapies by Mexican farmworkers; identifies the purposes and perceived helpfulness of these modalities; and delineates variation in the use of traditional healers and complementary therapies. Methods: Two-hundred Mexican farmworkers in North Carolina completed interviews May-September, 2017. The International Complementary and Alternative Medicine Questionnaire (I-CAM-Q) elicited use of conventional health-care providers, traditional healers, and complementary therapies in the previous 12 months. Results: Most of the farmworkers had been treated by a conventional provider (63.0%). One-in-five had been treated by any traditional healer; 19.5% had been treated by a sobador, 4.5% by a curandero, 2.0% by an herbalist, and 2.0% by a spiritual healer. Conventional providers (69.8%) and sobadores (84.6%) most often treated acute conditions; 62.5% had used an herb, 46.0% a vitamin, 57.0% an over-the-counter medicine, and 13.5% a home remedy. Participants used various self-care practices, including music (36.5%), sleep (18.0%), prayer for health (15.0%), and social media (14.0%). Education was inversely associated with the use of a traditional healer and herbs; treatment by a conventional health-care provider was positively associated with using a traditional healer and vitamins. Conclusions: Mexican farmworkers use conventional health-care providers as well as traditional healers and complementary therapies. Research on how use of complementary therapies and a system of medical pluralism affects farmworker health is needed. Health-care providers need to recognize complementary therapy use and provide patient education about ineffective or harmful therapies.

[Impairment of the hypothalamus and striatum of rats following lead exposure].

OBJECTIVE: To investigate the impairment of lead exposure on rat hypothalamus and striatum. METHODS: Forty-five healthy SPF male SD rats were randomly divided into three groups, control group( double distilled water), low( 60 mg/kg BW) and high dose( 120 mg/kg BW) groups. The rats were treated with lead acelate water solution in lead exposure group by gavage for 9 weeks. Open-field test was used to detect behavioral changes of the rats. The lead content of hypothalamus and striatum was determined by inductively coupled plasma mass spectrometry( ICP-MS). The mRNA expressions of toll-like receptor 4( TLR4), nuclear transcription factor kappa B( NF-κB), tumor necrosis factors alpha( TNF-α), interleukin-1( IL-1ß) and 8-oxoguanine DNA glycosylase( OGG1) were measured by real-time PCR. Enzyme linked immunosorbent assay( ELISA) was applied to detect the protein content of TLR4, NF-κB, TNF-α, IL-1ß and 8-hydroxy-2-deoxyguanosine( 8-OHd G). RESULTS: There were no significant differences in terms of body weight among three groups of rats. Compared with the control group, total movement distance, the total number of lattice and the distance of the central region in low and high lead exposure group were significantly decreased( P < 0. 05). The lead contents in hypothalamus and striatum of rats of low and high lead exposure group were( 60. 10 ± 6. 71), ( 71. 20 ± 11. 24), ( 44. 07 ± 9. 63)and( 66. 67 ± 8. 78) µg/g, respectively, higher than those in the control group(( 33. 77± 8. 19), ( 25. 75 ± 6. 33) µg/g)( P < 0. 05). While compared with the control group, the mRNA expression of NF-κB and OGG1 of the low and high lead exposure group were( 3. 47 ± 0. 15), ( 1. 43 ± 0. 16) and( 0. 67 ± 0. 13), ( 0. 57 ± 0. 19) folds in hypothalamus, there were marked differences in the mRNA expression of TLR4 and NF-κB between low and high lead group. The NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the low lead exposure group were( 5. 85 ± 1. 10), ( 56. 15 ± 6. 96) and( 1. 18 ± 0. 20) ng/g, respectively higher than those in control group(( 3. 03 ± 0. 71), ( 49. 25 ± 7. 21) and( 0. 86 ± 0. 11) ng/g)( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß protein contents in hypothalamus of the high lead exposure group were( 0. 67 ± 0. 12), ( 4. 74 ± 0. 68), ( 69. 73 ± 9. 61) and( 1. 43 ± 0. 29) ng/g, respectively, higher than those in control group. There were marked differences in the protein contents of TLR4 and TNF-α significant between low and high lead group in hypothalamus. The mRNA expression of TLR4, NF-κB, IL-1ß in the striatum of rats in the high lead exposure group were significantly higher than those in control group( P < 0. 05). The TLR4, NF-κB, TNF-α, IL-1ß, 8-OHd G protein contents of the high lead exposure group were( 0. 33 ±0. 02) ng/g, ( 4. 66 ± 0. 51), ( 82. 63 ± 7. 99), ( 1. 92 ± 0. 35) and( 1. 21 ± 0. 14) ng/g, respectively higher than those in control group( P < 0. 05), NF-κB protein content of the high lead exposure group was higher than that in low lead exposure group( P < 0. 05). CONCLUSION: Lead exposure does result in the impairment of hypothalamus and striatum, indicating that inflammation and oxidative damage might be involved in this process.

Vitamin D Status and Exercise Capacity in Older Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Older patients with heart failure with preserved ejection fraction have severe exercise intolerance. Vitamin D may play a role in cardiovascular and skeletal muscle function, and may therefore be implicated in exercise intolerance in heart failure with preserved ejection fraction. However, there are few data on vitamin D status and its relationship to exercise capacity in heart failure with preserved ejection fraction patients. METHODS: Plasma 25-hydroxyvitamin D (25[OH]D) and exercise capacity (peak oxygen consumption, [VO2], 6-minute walk distance) were measured in 112 older heart failure with preserved ejection fraction patients (mean ± SD age = 70 ± 8 years) and 37 healthy age-matched controls. General linear models were used to compare 25(OH)D between heart failure with preserved ejection fraction patients and healthy controls, and to determine the cross-sectional association between 25(OH)D and exercise capacity. The association between 25(OH)D and left ventricular function was evaluated secondarily in heart failure with preserved ejection fraction patients. RESULTS: 25(OH)D concentrations were significantly lower in heart failure with preserved ejection fraction vs healthy controls (11.4 ± 0.6 ng/mL vs 19.1 ± 2.1 ng/mL; P = .001, adjusted for age, race, sex, body mass index, season). More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency (<20 ng/mL) and 30% had frank 25(OH)D deficiency (<10 ng/mL). In heart failure with preserved ejection fraction patients, but not healthy controls, 25(OH)D was significantly correlated with peak VO2 (r = 0.26; P = 0.007) and 6-minute walk distance (r = 0.34; P < .001). CONCLUSIONS: More than 90% of heart failure with preserved ejection fraction patients had 25(OH)D insufficiency, and 30% were frankly deficient. Lower 25(OH)D was associated with lower peak VO2 and 6-minute walk distance in heart failure with preserved ejection fraction, suggesting that 25(OH)D insufficiency could contribute to exercise intolerance in this patient population. These findings provide the data and rationale for a future randomized trial designed to test the potential for vitamin D supplementation to improve exercise intolerance in heart failure with preserved ejection fraction.

SuHeXiang Essential Oil Inhalation Produces Antidepressant- and Anxiolytic-Like Effects in Adult Mice.

SuHeXiang (SHX) has been used to treat a wide range of diseases, including those related to the central nervous system. However, the effects of SHX on mood disorders are still elusive. This study aimed to investigate the effects of SHX essential oil on stress-induced depression of mice. In an acute stress-induced depression model, mice inhaled vehicle (1% Tween 80) for 10 min or 10% SHX for 10 or 30 min once daily for 12 continuous days. In the chronic mild stress (CMS)-induced depression model, mice were exposed to a 28-d CMS treatment. Tail suspension test (TST), forced swimming test (FST), sucrose preference test (SPT), open field test (OFT), and novelty suppressed feeding (NSF) test were conducted. In addition, serum levels of angiogenin (ANG), thrombopoietin (TPO), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were evaluated by enzyme-linked immunosorbent assay (ELISA) assays. The results showed that in mice exposed to acute stress, repeated SHX inhalation exerted significant antidepressant and anxiolytic activities, and also reduced the serum levels of ANG, TPO, IL-6, and TNF-α. It also significantly reversed the depressive and anxiety-like behaviors, and reduced the serum levels of ANG and TPO in mice exposed to CMS. This is the first report to show that SHX inhalation could produce significant antidepressant and anxiolytic-like effects. These effects might be mediated by SHX ability to modulate the inflammatory response, and reduce dysfunction of vascular genesis and thrombosis. These results support further exploration for developing SHX inhalation as a novel therapeutic strategy for depression and stress-related disorders.

Anti-inflammatory phenylpropanoids and phenolics from Ficus hirta Vahl.

Four new phenylpropanoids (1-4) along with ten known phenolics were isolated and purified from the roots of hairy fig (Ficus hirta Vahl.). Their structures were elucidated by the extensive spectroscopic analysis and chemical degradation. The anti-inflammatory activities of the purified compounds were evaluated. Results indicated that the extracts and some purified compounds exhibited pronounced inhibitory effects on the lipopolysaccharides (LPS) induced nitric oxide (NO) production in murine macrophage RAW 264.7 compared to indomethacin, which suggested that hairy fig could be served as an anti-inflammatory agent for health products.

Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs.

The current agents used for renal cell carcinoma (RCC) only exhibit the moderate response rate among patients. Development of drug resistance eventually fuels the need of either more potent drugs or new drugs to target the resistant pathways. Oridonin is a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens and has been shown to have antitumor activities in many cancers. We previously developed new synthetic methodologies to modify structurally diversified diterpenoids and designed a series of nitrogen-enriched oridonin analogs. In this study, we screened a variety of oridonin analogs based on their cytotoxicity using MTT assay and identify the most potent candidate, namely, CYD-6-17. CYD-6-17 exhibited a high potency to inhibit the in vitro growth of several drug-resistant RCC cells as well as endothelial cells stimulated by tumor cells at nanomolar range. Delivery of CYD-6-17 significantly inhibited RCC tumor growth using xenograft model. Mechanistically, it targeted the 3-phosphoinositide-dependent protein kinase 1 gene that appeared to be a potent regulator of AKT and was associated with patient survival after targeted therapies. This offers a new rational therapeutic regimen of CYD-6-17 to drug-resistant RCC based on its novel mechanism of action.

Association of platelet-activating factor receptor gene rs5938 (G/T) and rs313152 (T/C) polymorphisms with coronary heart disease and blood stasis syndrome in a Chinese Han population.

OBJECTIVE: To explore the association of the platelet-activating factor receptor (PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease (CHD) and blood stasis syndrome (BSS) of CHD in Chinese Han population. METHODS: A total of 570 CHD patients (299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaPshot technology. The statistical analysis was conducted using a multiple variable logistic regression model. RESULTS: Significant differences were detected in the genotypes frequency distributions of the rs5938 (P<0.01), but not the rs313152 (P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio (aOR)=0.35, 95% confidence interval (CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD (aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD (aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS (aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS (aOR=1.22, 95% CI: 0.81 to 1.85, P<0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27 (95% CI: 0.1 to 0.7, P<0.01). CONCLUSION: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.

Effectiveness of Chinese Hand Massage on Anxiety Among Patients Awaiting Coronary Angiography: A Randomized Controlled Trial.

BACKGROUND: Anxiety is the most common negative emotion among the patients awaiting coronary angiography. The increased anxiety may exacerbate coronary heart disease symptoms and possibly contribute to complications during the procedure. Chinese hand massage is a nonpharmaceutical intervention that has been used in several clinical situations in China and might have beneficial effects on reducing anxiety before coronary angiography. OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of Chinese hand massage care on anxiety among patients awaiting coronary angiography. METHODS: One hundred eighty-five subjects awaiting coronary angiography in a single hospital in Fuzhou, China, between May 2012 and September 2012 were screened. One hundred eligible participants were recruited and randomly assigned into the control or Chinese hand massage group. The control group received the conventional therapies and care according to the guidelines, and those in the Chinese hand massage group received additional Chinese hand massage care in conjunction with the same conventional therapies and care as the control group. The anxiety scores (evaluated by using the Hamilton Anxiety Rating Scale), heart rate, blood pressure, quality of life (Short-Form Health Survey), and the adverse events were recorded at the baseline and after coronary angiography, respectively. RESULTS: The scores of Hamilton Anxiety Rating Scale in the Chinese hand massage group (11.78 [SD, 2.9]) had a statistically significant decrease compared with those in the control group (15.96 [SD, 3.4]) at post-procedure (P < .01). There was no statistically significant difference on blood pressure, heart rate, and Short-Form Health Survey at postangiography between the Chinese hand massage group and the control group. No adverse event was reported during the intervention period. CONCLUSIONS: Chinese hand massage effectively alleviated anxiety without any adverse effects among patients awaiting coronary angiography. Therefore, it might be recommended as a nonpharmacological nursing intervention. However, future study with a larger sample size is needed to further confirm the efficacy of Chinese hand massage intervention.

[Root morphological characteristics of barley genotype with high phosphorus efficiency under phosphorus stress].

A pot experiment was carried out to test the effects of phosphorus (P) supply levels (25, 50, and 75 mg P2O5 . kg-1) with two P genotype (efficient DH110+ and DH147, inefficient DH49) barleys on root morphology and the relationships between root morphology and P uptake. The results showed that barley biomass and P uptake were significantly reduced by low P stress. Efficient genotype barley biomass and P uptake were 1.24-1.70 and 1.18-1.83 times as much as those of inefficient genotype barley respectively. The total root length, total root surface area, average root diameter, adventitious root length and root surface area, lateral root length and root surface area of P efficient genotype barley were significantly reduced with decreasing the P supply level in soil. The total root length, total root surface area, specific root length, lateral root length and surface area of P efficient genotype barley were 1.46-2.06, 1.12-1.51, 1.35-1.72, 1.69-2.42; and 1.40-1.78 times as much as that of those of P inefficient genotype barley, respectively, while the average root diameter was 70.6% - 90.2% of P inefficient genotype barley. Principal component analysis showed that the average root diameter, specific root surface area and specific root length could be used to distinguish two P genotype barleys. Partial least squares regression analysis showed that the total root length, total root surface area made great contributions to P uptake of barley in soil. The contribution of the adventitious root length and surface area on P uptake of barley decreased significantly and the average root diameter, specific root length, lateral root length and root surface area increased with the decreasing P supply level in soil. P efficient genotype barley adapted to low P stress through maintaining the lateral root growth, increasing the specific root length and root fineness.