Identification of Adulteration of Flaxseed Oil From QINGHAI Area Using GC-MS Profiling of Phytosterol Composition and Chemometrics.

Flaxseed oil is an important source of vegetable oil with a polyunsaturated fatty acid. It is significant to establish a method to quickly identify adulterated flaxseed oil. In the present study, the qualitative and quantitative analysis of phytosterol of flaxseed oil from different varieties and different production areas in the Qinghai area was first performed by gas chromatography-mass spectrometry (GC-MS) and the phytosterol standard profile of flaxseed oil was established. Then, a combination of similarity evaluation and cluster analysis was used to distinguish pure flaxseed oil from flaxseed oil adulterated with concentrations of 10-50% rapeseed oil, peanut oil, sunflower oil, and sesame oil, and discriminant analysis was used to identify the types of adulterated flaxseed oil. The results showed that similarity evaluation combined with cluster analysis can distinguish pure and adulterated flaxseed oil when the concentration of the adulterant was greater than 10%. Discriminant analysis models accurately identified the types of adulterating oil in flaxseed oil when the concentration of rapeseed, peanut, or sunflower oil was greater than 20%, and that of sesame oil was greater than 30%. This study shows that the determination of the phytosterol composition and chemometrics is a valuable tool to evaluate the purity of flaxseed oil.

Health-Promoting Activities and Associated Mechanisms of Polygonati Rhizoma Polysaccharides.

Polygonati Rhizoma, a typical homology of medicine and food, possesses remarkable anti-fatigue, anti-aging, metabolic regulatory, immunomodulatory, anti-inflammatory, neuroprotective, anti-diabetes, and anti-cancer effects. Among bioactive phytochemicals in Polygonati Rhizoma, polysaccharides play important roles in the health-promoting activities through the mechanisms mentioned above and potential synergistic effects with other bioactives. In this review, we briefly introduce the updated biosynthesis of polysaccharides, the purification method, the structure characterization, and food applications, and discuss in detail the biological activities of Polygonati Rhizoma polysaccharides and associated mechanisms, aiming at broadening the usage of Polygonati Rhizoma as functional food and medicine.

Immunomodulatory effects and associated mechanisms of Momordica charantia and its phytochemicals.

Momordica charantia L. (M. charantia), which is a member of the Cucurbitaceae family and widely distributed in tropical and subtropical regions, has been consumed as a vegetable and also used as herbal medicine for thousands of years worldwide. M. charantia has received great attention in biological and biomedical research due to its remarkable antidiabetic/hypoglycaemic, anti-inflammatory, antioxidant, antiviral and antitumour activities both in vivo and in vitro. Numerous studies have revealed that the typical health-promoting activities of M. charantia are mainly attributed to its phytochemicals including saponins, proteins/peptides, phenolic compounds, alkaloids, triterpenoids and polysaccharides. In particular, it has been attested that there is a strong relationship between the antidiabetic activity and the saponins and proteins of M. charantia. In recent years, studies on the immunoenhancing and immunostimulating effects of M. charantia have attracted much attention and made significant progress. Therefore, this review focuses on the immunomodulatory effects and associated mechanisms of M. charantia and its bioactive phytochemicals. The clinical applications of M. charantia in immune-related diseases are also discussed, aiming to broaden the exploration of M. charantia as a functional food.

Demethylzeylasteral attenuates hepatic stellate cell activation and liver fibrosis by inhibiting AGAP2 mediated signaling.

BACKGROUND: Liver fibrosis is a common cause of chronic liver disease. If left untreated, it can ultimately develop into liver cirrhosis or hepatocellular carcinoma. However, a direct antifibrotic therapy is currently unavailable. A re-examination of existing chemicals might be a potential strategy for finding more lead compounds against liver fibrosis. Demethylzeylasteral (T-96), a naturally occurring bioactive compound found in Tripterygium wilfordii Hook. f. (TwHf) possesses multiple pharmacological properties. However, its antifibrotic potential has not yet been fully evaluated. PURPOSE: This study aimed to investigate the antifibrotic properties of T-96 and its underlying molecular mechanisms. METHODS: The antifibrotic properties of T-96 were investigated in three types of hepatic stellate cells (HSCs) and in a CCl4-induced liver fibrosis mouse model. The effect of T-96 on the proliferation, migration, and activation of HSCs was detected using CCK-8 and scratch/wound healing assays. Hepatic inflammation and fibrosis were evaluated by H&E, Masson's trichrome stain, and Sirius Red staining. The expression of inflammatory and fibrogenic genes was detected by quantitative real-time PCR (qRT-PCR) and western blotting. RNA sequencing (RNA-seq) was performed to explore the potential molecular mechanisms mediating the antifibrotic effect of T-96, which was verified by dual-luciferase reporter assay, qRT-PCR, western blotting, immunofluorescence, and immunoprecipitation analysis. RESULTS: The T-96 treatment significantly suppressed the proliferation, migration, and activation of HSCs in vitro. The administration of T-96 attenuated hepatic injury, inflammation, and fibrosis progression in mice with CCl4-induced liver fibrosis. In addition, the RNA-seq of fibrotic liver tissues and subsequent functional verification indicated that the key mechanisms of the antifibrotic effect of T-96 were mediated by suppressing the expression of AGAP2 (Arf GAP with GTPase-like domain, ankyrin repeat and PH domain 2), inhibiting the subsequent phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT), and finally reducing the expression of fibrosis-related genes. CONCLUSION: Our results provide the first insight that T-96 exerts potent antifibrotic effects both in vitro and in vivo by inhibiting the AGAP2 mediated FAK/AKT signaling axis, and that T-96 may serve as a potential therapeutic candidate for the treatment of liver fibrosis.

Bioactives of Momordica charantia as Potential Anti-Diabetic/Hypoglycemic Agents.

Momordica charantia L., a member of the Curcubitaceae family, has traditionally been used as herbal medicine and as a vegetable. Functional ingredients of M. charantia play important roles in body health and human nutrition, which can be used directly or indirectly in treating or preventing hyperglycemia-related chronic diseases in humans. The hypoglycemic effects of M. charantia have been known for years. In this paper, the research progress of M. charantia phytobioactives and their hypoglycemic effects and related mechanisms, especially relating to diabetes mellitus, has been reviewed. Moreover, the clinical application of M. charantia in treating diabetes mellitus is also discussed, hoping to broaden the application of M. charantia as functional food.

Immunomodulatory Effects of Green Tea Polyphenols.

Green tea and its bioactive components, especially polyphenols, possess many health-promoting and disease-preventing benefits, especially anti-inflammatory, antioxidant, anticancer, and metabolic modulation effects with multi-target modes of action. However, the effect of tea polyphenols on immune function has not been well studied. Moreover, the underlying cellular and molecular mechanisms mediating immunoregulation are not well understood. This review summarizes the recent studies on the immune-potentiating effects and corresponding mechanisms of tea polyphenols, especially the main components of (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG). In addition, the benefits towards immune-related diseases, such as autoimmune diseases, cutaneous-related immune diseases, and obesity-related immune diseases, have been discussed.

[Study on rat intestinal absorption characteristics of total flavonoids from Coreopsis tinctoria].

The rat everted intestinal sac model was adopted to investigate the absorption of total flavonoids from Coreopsis tinctoria in different intestinal segments. Cyaniding-3-O-ß-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, iso-okanin, marein and 3,5-dicaffeoylquinic acid which as the major chemical components of total flavonoids from C. tinctoria were selec-ted as the study objects to evaluate the absorption characteristics of each component in different intestinal segments. The results showed that the absorption of seven components of total flavonoids at different intestinal segments was in consistent with zero order absorption rate. The K_a of chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, isookanin and 3,5-dicaffeoylquinic acid increased with increasing of concentration of total flavonoids(P<0.05), indicating that the intestinal absorption of these five components was passive transport. The K_a of cyaniding-3-O-ß-D-glucoside and marein showed a weak concentration dependence, suggesting that the absorption of them may be an positive and passive co-existing mode. The result of absorption in different intestinal segments showed that cyaniding-3-O-ß-D-glucoside, chlorogenic acid, flavanomarein, quercetagetin-7-O-ß-D-glucoside, marein and 3,5-dicaffeoylquinic acid were mainly absorbed in ileum, while isookanin was mainly absorbed in jejunum. The total flavonoids of C. tinctoria are selectively absorbed in intestinal tract, the rat everted intestinal sac model can be used to evaluate the multi-component intestinal absorption characteristics of total flavonoids from C. tinctoria.

Polyphenol-Enriched Extracts from Trapa acornis Husks Inhibit Her2-Positive SK-BR-3 Breast Cancer Cell Proliferation and In Vivo Tumor Angiogenesis.

The study aimed to investigate the antitumor effects of Trapa acornis husks (TAH) extract on SK-BR-3 cells of Her2-positive breast cancer. The bioactive compounds of TAH extracts were analyzed qualitatively and quantitatively by Ultra-Performance Liquid Chromatography/Mass Spectrometry (UPLC-MS)/high-performance liquid chromatographic system (HPLC). The effects of TAH extracts on cell proliferation, cell cycle, and apoptosis of SK-BR-3 cells were determined by CCK-8 and flow cytometry. Besides, the In Vivo antitumor effect of TAH extracts was detected. UPLC-MS/HPLC showed that the main bioactive compounds of TAH were gallic acid and galloylglucose derivatives. TAH extracts significantly inhibited the proliferation of SK-BR-3 cells in a dose- and time-dependent manner (P < 0.01). With the increase of TAH extracts concentration, cells in G2/M stage were increased and cell apoptosis was significantly increased. Immunohistochemical analysis showed that TAH extracts can significantly reduce the positive expression rate of Ki67 and Factor VIII index in tumor tissues. The mRNA expression levels of VEGF, MMP2, MMP9, and uPA were reduced after TAH extracts intervention (P < 0.01). TAH extracts also decreased the protein expression of p-Her2, p-ERK1/2, VEGF, MMP2, MMP9, and uPA (P < 0.01). In conclusion, polyphenol-enriched extracts from TAH might inhibit breast cancer cell proliferation and In Vivo tumor angiogenesis.

Regulatory effects of Ningdong granule on microglia-mediated neuroinflammation in a rat model of Tourette's syndrome.

Tourette's syndrome (TS) is an inherited neurologic disorder characterized by involuntary stereotyped motor and vocal tics. Its pathogenesis is still unclear and its treatment remains limited. Recent research has suggested the involvement of immune mechanisms in the pathophysiology of TS. Microglia are the brain's resident innate immune cells. They can mediate neuroinflammation and regulate brain development and homeostasis. A traditional Chinese medicine (TCM), Ningdong granule (NDG), has been found to be efficacious in the treatment of TS while causing few adverse reactions. In the current study, a rat model of 3,3'-iminodipropionitrile (IDPN)-induced TS was used to explore the regulating effects and mechanisms of NDG on microglia-mediated neuroinflammation. IDNP led to robust pathological changes and neurobehavioral complications, with activation of microglia in the striatum of rats with TS. After activation by IDNP, microglia strongly responded to this specific injury, and TNF-α, IL-6, and MCP-1 were released in the striatum and/or serum of rats with TS. Interestingly, NDG inhibited the activation of microglia and decreased the abnormal expression of TNF-α, IL-6, and MCP-1 in the striatum and/or serum of rats with TS, thus controlling tics. However, there were no significant changes in the striatum and/or serum of rats with TS after treatment with haloperidol. The anti-TS action of haloperidol might occur not through microglial activation and neuroinflammation but through the DAT system, thus controlling tics. In conclusion, microglia might play key roles in mediating neuroinflammatory responses in TS, triggering the release of TNF-α, IL-6, and MCP-1.NDG inhibited tics in rats with TS, and this mechanism may be associated with a reduction in the increased number of activated microglia and a decrease in the expression of pro-inflammatory cytokines and chemokines in the striatum and/or serum.

Momordica charantia: a popular health-promoting vegetable with multifunctionality.

Products derived from edible medicinal plants have been used for centuries to prevent, treat, and even cure multiple diseases. Momordica charantia L., widely cultivated around the world, is a typical one bred for vegetables and medicinal usage. All parts of M. charantia possess important medicinal properties, including antidiabetic, anticancer, hypotensive, anti-obesity, antimicrobial, antihyperlipidemic, antioxidant, anti-inflammatory, immuno-modulatory, anthelmintic, neuro-protective, as well as hepato-protective properties both in vitro and in vivo. This review summarizes the active components and medicinal properties of M. charantia, especially the activities and mechanisms of its anti-diabetic and anti-cancer properties. The anti-diabetic properties involve inhibiting intestinal α-glucosidase and glucose transport, protecting islet ß-cells, enhancing insulin secretion, increasing hepatic glucose disposal, decreasing gluconeogenesis, and even ameliorating insulin resistance. Moreover, the expressions of PPARs could also be activated and up-regulated. Meanwhile, its anticancer properties are mostly due to apoptosis, cell cycle arrest, and expression of serum factors associated with immunity. In this review, we aim to provide an overview of M. charantia and its benefits for development as a functional food.

Astragaloside IV attenuates inflammatory reaction via activating immune function of regulatory T-cells inhibited by HMGB1 in mice.

CONTEXT: High-mobility group box 1 (HMGB1) protein is a highly abundant protein that can promote the pathogenesis of inflammatory. Some experiments have demonstrated a vital role for HMGB1 to modulate the immune function of regulatory T-cells (Tregs). Astragaloside IV (AST IV), an extract from Astragalus membranaceus Moench (Leguminosae), has been shown to exert potent cardioprotective and anti-inflammatory effects. It is still unclear whether AST IV has a latent effect on the proinflammatory ability of HMGB1 with subsequent activation of Tregs in vivo. OBJECTIVE: This research explores the antagonism of different doses of AST IV on the immunologic function of Tregs mediated by HMGB1. MATERIALS AND METHODS: Mouse models (BALB/c) were constructed by which normal saline or AST IV was administered i.p. at 2, 4 and 6 days after the administration i.p. of 20 µg recombinate HMGB1. Spleen was used to procure Treg and CD4 + CD25- T-cells which were co-cultured with Treg. Cell phenotypes of Tregs(Foxp3) were examined, and the cytokine levels in supernatants and the proliferation of T-cells were assayed. Gene expression was measured by RT-PCR. RESULTS: (1) The expression levels of Foxp3 in Treg on post-stimulus days (PSD) 1-7 were significantly decreased in the HMGB1 group in comparison to those in the control group mice (p < 0.01). The Foxp3 expression was markedly increased in a dose-dependent manner in the AST group as compared with those in the HMGB1 group (p < 0.0 1-0.05). The same results were found in the contents of cytokines (IL-10 and TGF-ß) released into supernatants by Treg. (2) When CD4 + CD25- T-cells were co-cultured with Treg stimulated by HMGB1, the cell proliferation and the levels of cytokines (IL-2 and IFN-γ) in supernatant were markedly increased as compared with those in the HMGB1 group. The level of IL-4 was markedly decreased as compared with that in the HMGB1 group. The same results were found when CD4 + CD25- T-cells were co-cultured with Treg in the NS group. Compared with those in the NS group, the contrary results were shown in a dose-dependent manner in the AST group. DISCUSSION AND CONCLUSION: These results showed that AST IV has a therapeutic effect on inflammation promoted by HMGB1, and it should be studied as a new drug for the treatment of sepsis.

Antifungal activity of Momordica charantia seed extracts toward the pathogenic fungus Fusarium solani L.

Momordica charantia L., a vegetable crop with high nutritional value, has been used as an antimutagenic, antihelminthic, anticancer, antifertility, and antidiabetic agent in traditional folk medicine. In this study, the antifungal activity of M. charantia seed extract toward Fusarium solani L. was evaluated. Results showed that M. charantia seed extract effectively inhibited the mycelial growth of F. solani, with a 50% inhibitory rate (IC50) value of 108.934 µg/mL. Further analysis with optical microscopy and fluorescence microscopy revealed that the seed extract led to deformation of cells with irregular budding, loss of integrity of cell wall, as well as disruption of the fungal cell membrane. In addition, genomic DNA was also severely affected, as small DNA fragments shorter than 50 bp appeared on agarose gel. These findings implied that M. charantia seed extract containing α-momorcharin, a typical ribosome-inactivating protein, could be an effective agent in the control of fungal pathogens, and such natural products would represent a sustainable alternative to the use of synthetic fungicides.

The importance of start codon of nosM in nosiheptide production.

The present study was designed to investigate the effects of start codon of nosM on the biosynthesis of nosiheptide. Target genes were amplified by overlap PCR. After homologous recombination to construct engineered strains, nosiheptide production was analyzed by HPLC. Three mutants with different start codon of nosM were constructed, and nosiheptide production of each mutant was analyzed and compared. Replacement of the start codon of nosM significantly decreased the production of nosiheptide. In conclusion, start codon usage could greatly affect the biosynthetic efficiency in the biosynthetic gene cluster of nosiheptide.

Pollen developmental defects in ZD-CMS rice line explored by cytological, molecular and proteomic approaches.

Cytoplasmic male sterility (CMS) is a widely observed phenomenon, which is especially useful in hybrid seed production. Meixiang A (MxA) is a new rice CMS line derived from a pollen-free sterile line named Yunnan ZidaoA (ZD-CMS). In this study, a homologous WA352 gene with variation in two nucleotides was identified in MxA. Cytological analysis revealed that MxA was aborted in the early uninucleate stage. The protein expression profiles of MxA and its maintainer line MeixiangB (MxB) were systematically compared using iTRAQ-based quantitative proteomics technology using young florets at the early uninucleate stage. A total of 688 proteins were quantified in both rice lines, and 45 of these proteins were found to be differentially expressed. Bioinformatics analysis indicated a large number of the proteins involved in carbohydrate metabolism or the stress response were downregulated in MxA, suggesting that these metabolic processes had been hindered during pollen development in MxA. The ROS (reactive oxygen species) level was increased in the mitochondrion of MxA, and further ultrastructural analysis showed the mitochondria with disrupted cristae in the rice CMS line MxA. These findings substantially contribute to our knowledge of pollen developmental defects in ZD-CMS rice line. BIOLOGICAL SIGNIFICANCE: MeixiangA (MxA) is a new type of rice CMS line, which is derived from pollen-free sterile line Yunnan ZidaoA. In this study, the cytological, molecular and proteomic approaches were used to study the characteristics of this new CMS line. Cytological study indicates the CMS line is aborted at the early uninucleate stage. A potential sterile gene ZD352 is identified in MxA, the protein product of which is mainly accumulated at the MMC/Meiotic stage. iTRAQ based proteomic analysis is performed to study the relevant proteins involved in the CMS occurance, 45 proteins are found to be significant differentially expressed and these proteins are involved in many cellular processes such as carbohydrate metabolism, stress response, protein synthesis. To our knowledge, this is the first report using the iTRAQ-labeled quantitative proteomic to study the protein expression variation during the abortion processes between a CMS line and its maintainer line. These results provide new insights on the CMS mechanisms of ZD-CMS rice line.

Toosendanin induces apoptosis through suppression of JNK signaling pathway in HL-60 cells.

Toosendanin (TSN), a triterpenoid isolated from Melia toosendan Sieb. et Zucc., has been found to suppress proliferation and induce apoptosis in a variety of human cancer cells. However, the mechanism how TSN induces apoptosis remains poorly understood. In this study, we examined the effects of TSN on the growth, cell cycle arrest, induction of apoptosis and the involved signaling pathway in human promyelocytic leukemia HL-60 cells. Proliferation of HL-60 cells was inhibited in a dose-dependent manner with the IC(50 (48 h)) of 28 ng/mL. The growth inhibition was due primarily to the S phase arrest and cell apoptosis. Cell apoptosis induced by TSN was confirmed by Annexin V-FITC/propidium iodide staining. The increase of the pro-apoptotic protein Bax, cleaved PARP and caspase-3, and the decrease of anti-apoptotic protein Bcl-2 were observed. Western blot analysis indicated that TSN inhibits the CDC42/MEKK1/JNK pathway. Taken together, our study suggested, for the first time, that the pro-apoptotic effects of TSN on HL-60 cells were mediated through JNK signaling pathway.

Effects of Chinese herbal medicine Ningdong granule on regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA) in patients with Tourette syndrome.

Many studies have indicated that a variety of neurotransmitters are implicated in the pathophysiology of Tourette syndrome (TS), including dopamine (DA), serotonin (5-TH), homovanillic acid (HVA), and gamma-amino butyric acid (GABA). Our previous studies found that Ningdong granule (NDG) is effective on a rat model with TS. NDG can regulate the metabolic disturbance of DA, 5-TH and HVA in the rat brain. However, the mechanisms of NDG in patients with TS are still not clear. To further evaluate the efficiency, safety, and possible mechanisms of NDG, a randomized and double-blind study was carried out. One hundred and twenty patients with TS were enrolled in this study, that were randomly divided into 4 groups (NDG group, Haloperidol (Hal) group, NDG + Hal group and Control group). First, the efficiency of NDG was assessed using the Yale Global Tic Severity Score (YGTSS). Second, the concentration of DA, HVA, 5-TH, 5-hydroxyindoleacetic acid (5-HIAA) and GABA in sera were tested by ELISA. In addition, the influence of NDG on liver and renal function was recorded. We found that NDG could ameliorate tics significantly according the YGTSS score. The concentration of HVA and GABA were increased after treatment with NDG. Furthermore, we found that there was no liver or renal damage in children treated with NDG. We also found that the NDG + Hal group was more effective and safe compared with other groups. In conclusion, the current study indicates that NDG might be effective on patients with TS by regulating dopamine (DA)/serotonin (5-TH) and gamma-amino butyric acid (GABA).

[Clinical characteristics of drug-induced liver injury in 31 pediatric cases].

OBJECTIVE: To investigate the clinical characteristics and responsible agents of drug-induced liver injury (DILI) in pediatric patients. METHODS: Thirty-one cases of DILI treated in our hospital's pediatric ward were retrospectively analyzed. The clinical data for each patient were extracted from the patient's medical records, and included reported causes, physical and biochemical features, natural history, blood examination results, and hepatic pathology findings. RESULTS: The 31 pediatric cases of DILI accounted for 1.7% of the 1831 total cases of drug-induced liver injury treated at our hospital between February 2002 to June 2011. The pediatric DILI population was composed of 20 males and 11 females, with an average age of 8.8+/-3.9 years old (range, 0.3-14.0). The liver injury patterns represented among the cases were: hepatocellular (25.8%), cholestasis (25.8%), and mixed hepatocellular-cholestatic (48.4%). Antimicrobials were the most common cause (41.9%) of DILI, followed by the herbal medicine (29.0%) and febrifuge drugs (19.4%). A single drug was implicated in nine cases (29.0%), and two or more drugs were implicated in 22 cases (71%). Most of the children had good prognosis, but those with pre-existing disease had poor prognosis. One child died of hepatic failure, making the death rate 3.23%. The average hospitalization time was 25.2 days, and the patients with hepatocellular injury had shorter hospitalization time than those with mixed injury. CONCLUSION: Drug-induced liver injury in our pediatric population was most often caused by antimicrobials, followed by herbal medicine and febrifuge drugs. Most patients presented with mixed hepatocellular-cholestatic injury. Children with pre-existing diseases or hepatic failure had poor prognosis.

Heart rate variability biofeedback decreases blood pressure in prehypertensive subjects by improving autonomic function and baroreflex.

BACKGROUND: Individuals with prehypertension are at risk of hypertension and cardiovascular diseases, and yet efficient interventions are lagging behind. Studies indicate that heart rate variability-biofeedback (HRV-BF) increases HRV and baroreflex sensitivity (BRS) as well as reduces related pathological symptoms, suggesting potentially beneficial effects of HRV-BF on prehypertension, but little is known about these effects. In this study, these effects were investigated and their mechanisms were explored. OBJECTIVES: The effect of HRV-BF on prehypertension in young adults and its potential mechanism were explored. DESIGN: Forty-three (43) individuals with prehypertension were recruited and classified into three categories: HRV-BF group, slow abdominal breathing group, and control group. All groups were assessed with measurements of noninvasive blood pressure (BP), BRS, respiration, and galvanic skin response (GSR) at pre-intervention, in the entire process of each session, at postintervention, as well as at a 3-month follow-up. INTERVENTIONS: Subjects participated in a 10-session HRV-BF protocol or simple slow abdominal breathing protocol conducted over 5 weeks. A 3-month follow-up was also performed on these individuals. RESULTS: The incidence of prehypertension was as high as 14.5% in young college students. Individuals with prehypertension were lower in BRS (7.5±5.2 ms/mm Hg) and HRV (log10-transformed of the standard deviation of normal-to-normal beats [SDNN]=1.62±0.13 ms, lgTotal power of spectral density in the range of frequencies between 0 and 0.4Hz (TP)=8.02±0.55 ms2) than those with normal blood pressure (BRS=18.4±7.4 ms/mm Hg, lgSDNN=1.79±0.10 ms, lgTP=8.68±0.85 ms2). HRV-BF reduced blood pressure (from 131.7±8.7/79.3±4.7 mm Hg to 118.9±7.3 mm Hg/71.9±4.9 mm Hg, p<0.01), increased BRS (from 7.0±5.9 ms/mm Hg to 15.8±5.3 ms/mm Hg, p<0.01) and increased HRV (lgSDNN from 1.61±0.11 to 1.75±0.05 ms, and lgTP from 8.07±0.54 to 9.08±0.41 ms2, p<0.01). These effects were more obvious than those of the slow-breathing group, and remained for at least 3 months. HRV-BF also significantly increased vagus-associated HRV indices and decreased GSR (indices of sympathetic tone). CONCLUSIONS: These effects suggest that HRV-BF, a novel behavioral neurocardiac intervention, could enhance BRS, improve the cardiac autonomic tone, and facilitate BP adjustment for individuals with prehypertension.

The apoptotic effects of toosendanin are partially mediated by activation of deoxycytidine kinase in HL-60 cells.

Triterpenoid toosendanin (TSN) exhibits potent cytotoxic activity through inducing apoptosis in a variety of cancer cell lines. However, the target and mechanism of the apoptotic effects by TSN remain unknown. In this study, we captured a specific binding protein of TSN in HL-60 cells by serial affinity chromatography and further identified it as deoxycytidine kinase (dCK). Combination of direct activation of dCK and inhibition of TSN-induced apoptosis by a dCK inhibitor confirmed that dCK is a target for TSN partially responsible for the apoptosis in HL-60 cells. Moreover, the activation of dCK by TSN was a result of conformational change, rather than auto-phosphorylation. Our results further imply that, in addition to the dATP increase by dCK activation in tumor cells, dCK may also involve in the apoptotic regulation.