Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure / 中国结合医学杂志

OBJECTIVE@#To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects.@*METHODS@#Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS).@*RESULTS@#In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05).@*CONCLUSION@#BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Poor Status of Vitamin D: A Survey of Area With Lowest Sunlight Radiation in Sichuan, China.

Objective: Vitamin D plays an important role in bone and mineral metabolism. Ultraviolet B (UVB) is the primary determinant for vitamin D synthesis. However, population-based data of vitamin D status was sparse in areas with sunlight deprivation in China. This study aimed to assess serum 25-hydroxyvitamin D [25(OH)D] levels among adult women in Sichuan basin with the lowest sunlight radiation in China, and the associations with sunlight exposure and age. Methods: In the context of the same ethnicity, similar latitude and lifestyle in sunlight-limited basin and sunlight-abundant plateau, 1,057 women in basin and 337 in plateau aged 29-95 years were included in this study, from November 2012 to February 2013. Daily sunlight exposure duration of previous month was obtained using questionnaires. Serum 25(OH)D was measured by enzyme-linked immunosorbent assay. Results: The prevalence of vitamin D severe deficiency [25(OH)D <30 nmol/L] and deficiency [30 ≤ 25(OH)D <50 nmol/L] was significantly higher in basin than plateau (21.85% vs. 10.09%, and 59.32% vs. 40.36%; P<0.0001). Women from basin exhibited lower serum 25(OH)D levels than those from plateau (40.66 ± 15.62 vs. 52.54 ± 19.94 nmol/L, P<0.0001). In basin, women more than 50 years old had higher 25(OH)D than younger counterparts, and 25(OH)D level of these groups was not associated with sunlight exposure duration. While in plateau, women younger than 60 years old had higher 25(OH)D than the older women. Furthermore, for those younger groups, women with long sunlight exposure (≥3 h daily) had higher 25(OH)D concentration than those with short sunlight exposure (<3 h daily). Serum PTH was negatively associated with 25(OH)D in basin, but not in plateau. Conclusions: Alarmingly high prevalence of vitamin D deficiency was observed in women in sunlight-deprived basin in Sichuan. Only the vitamin D status of younger women from plateau with adequate solar radiation could benefit from sunlight exposure. Vitamin D supplementation and vitamin D-fortified food should be encouraged to improve vitamin D status for women living in sunlight-limited areas, or with old age.

Oral cholecalciferol supplementation alleviates lipopolysaccharide-induced preterm delivery partially through regulating placental steroid hormones and prostaglandins in mice.

Several epidemiological reports demonstrated that vitamin D deficiency elevated risk of preterm delivery. We investigate the effects of oral cholecalciferol (VD3) supplementation on lipopolysaccharide (LPS)-induced preterm delivery. Pregnant mice were randomly assigned to either oral VD3 (25 µg/kg) or corn oil once daily from gestational day (GD)13 to GD15, and were intraperitoneally injected with either LPS (200 µg/kg) or normal saline on GD15. As expected, LPS was effective in inducing preterm delivery and fetal death. LPS-induced preterm delivery and fetal death were alleviated in VD3-pretreated mice. LPS-induced down-regulation of genes for placental progesterone biosynthetic enzymes was blocked in VD3-pretreated mice. LPS-induced reduction of serum progesterone was correspondingly attenuated by VD3. Although oral VD3 had no effect on estradiol production, it attenuated LPS-induced up-regulation of placental ERß in mice. LPS-induced placental COX-2 up-regulation and serum PGF2α elevation were alleviated in VD3-pretreated mice. Additionally, LPS-evoked elevations of the placental Tnfα, Il1ß, Mcp1 and Mip2 mRNAs were attenuated by VD3. VD3 promoted placental vitamin D receptor nuclear translocation and simultaneously alleviated LPS-induced nuclear translocation of NF-κB p65 and p50 subunits. These results provide evidence that oral VD3 supplementation alleviates LPS-induced preterm delivery and fetal demise partially through regulating placental steroid hormones and prostaglandins.

Understanding inter-organizational trust among integrated care service provider networks: A perspective on organizational asymmetries.

OBJECTIVE: To explore the factors that influence trust among the integrated healthcare service provider network in the context of seeking combined health and care services in the UK. DATA SOURCES/STUDY SETTING: Primary data were collected from three regional integrated care service provider networks from March 2016 to October 2017. STUDY DESIGN: Explorative qualitative study and inductive methods from emerging findings. DATA COLLECTION/EXTRACTION METHODS: We conducted qualitative semi-structured interviews in three care networks and collected organizational documents from local integration boards from 2016 to 2017. Thematic analysis was performed in three large care networks with hospital staff, local councils, integration boards, and community and voluntary organizations under the NHS England Better Care Fund. PRINCIPAL FINDINGS: Our findings reveal that trust among integrated care service provider networks is influenced by the following factors on various asymmetries: 1) recognition and knowledge asymmetries among care service partners of each other's skills, expertise and capabilities; 2) capacity and financial imbalances within the network; and 3) organizational differences in management, culture and attitudes toward change. CONCLUSION: There is a need to improve competence recognition and capacity imbalances and to foster open minds toward change within networks to build trust to overcome divisions and facilitate integrated services among health and care organizations.

Vitamin D deficiency impairs neurobehavioral development in male mice.

Vitamin D deficiency is prevalent especially in pregnant women and children. Several studies found that vitamin D status was negatively correlated with risk of senile neurobehavioral abnormality. The aim of this study was to investigate the effects of vitamin D deficiency on neurobehavioral development in mice. In vitamin D deficiency group, dams and their male pups were fed with vitamin D deficient (VDD) diet, in which vitamin D was depleted. Anxiety-related behavior, depressive-like behavior, spatial learning and memory were measured. As expected, serum 25(OH)D level was reduced in VDD diet-fed mice. An anhedonia state, a key depressive-like behavior, was observed in VDD diet-fed mice. In open-field test, peripheral time was decreased and internal time was increased in VDD diet-fed mice. In elevated plus maze, the latency of the first entry into open arms was increased and the number of crossing in open arms was elevated in VDD diet-fed mice. Morris Water Maze showed that VDD-fed mice showed longer escape latency in the first six days. On the seventh day, escape latency was increased in VDD diet-fed mice. These results provide evidence that vitamin D deficiency impairs neurobehavioral development.

Cadmium toxicity to Microcystis aeruginosa PCC 7806 and its microcystin-lacking mutant.

The adverse effects of microcystin (MC) produced by cyanobacteria have drawn considerable attention from the public. Yet it remains unclear whether MC confers any benefits to the cyanobacteria themselves. One suggested function of MC is complexation, which may influence the bioaccumulation and toxicity of trace metals. To test this hypothesis, we examined Cd toxicity to wild-type Microcystis aeruginosa PCC 7806 (WT) and its MC-lacking mutant (MT) under nutrient-enriched (+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The accumulation of Cd and the biochemical parameters associated with its detoxification [total phosphorus (TP), inorganic polyphosphate (Poly-P), and glutathione (GSH) in the cells as well as intra- and extra-cellular carbohydrates] were quantified. Although the -P cyanobacteria accumulated less Cd than their +NP and -N counterparts, the different nutrient-conditioned cyanobacteria were similarly inhibited by similar free ion concentration of Cd in the medium ([Cd2+]F). Such good toxicity predictability of [Cd2+]F was ascribed to the synchronous decrease in the intracellular concentrations of Cd and TP. Nevertheless, Cd toxicity was still determined by the intracellular Cd to phosphorus ratio (Cd/P), in accordance with what has been reported in the literature. On the other hand, the concentrations of TP, Poly-P, and carbohydrates went up, but GSH concentration dropped down with the enhancement of [Cd2+]F, indicating their association with Cd detoxification. Although the inactivation of MC peptide synthetase gene had some nutrient and Cd concentration dependent effects on the parameters above, both cyanobacterial strains showed the same Cd accumulation ability and displayed similar Cd sensitivity. These results suggest that MC cannot affect metal toxicity either by regulating metal accumulation or by altering the detoxification ability of the cyanobacteria. Other possible functions of MC need to be further investigated.

[Decomposition and nutrient release of root with different diameters of three subalpine dominant trees in western area of Sichuan Province, China].

In this study, a buried bag experiment was used to investigate mass loss and C, N and P release patterns of fine (≤2 mm), medium (2-5 mm) and coarse (≥ 5 mm) roots of 3 subalpine dominant trees, i. e., Betula albosinensis, Abies faxoniana and Picea asperata in the growing and non-growing seasons. In general, the remaining mass of B. albosinensis was lower than that of A. faxoniana and P. asperata. In addition, root remaining mass increased with the increase of root diameter for the same species. The mass losing rate in the non-growing season was 52.1%-64.4% of a year. The C release of B. albosinensis was the highest, but that of A. faxoniana was the lowest. Also, C release decreased with the increase of root diameter. N of A. faxoniana and P. asperata were enriched in the non-growing season but released in the growing season. However, the opposite pattern was found for B. albosinensis. During the non-growing season, the amount of N enrichment increased with the increase of root diameter. The P release of 3 species was characterized as the enrichment-release pattern. P enrichment of A. faxoniana was significantly greater than that of P. asperata and B. albosinensis. Nevertheless, no significant difference was observed between diameter sizes. In conclusion, diameter size had significant effect on root decomposition in the subalpine forests of western Sichuan, and the diameter effect was dependent on tree species and season.

Effects of nitrogen and phosphorus on arsenite accumulation, oxidation, and toxicity in Chlamydomonas reinhardtii.

We studied arsenite (iAs(III)) accumulation, oxidation, and toxicity in the freshwater green alga Chlamydomonas reinhardtii under nutrient-enriched (+NP), phosphorus-limited (-P), and nitrogen-limited (-N) conditions. The -P alga (55.1 µM) had a Michaelis constant (Kd) for uptake approximately one tenth of the +NP (419 µM) and -N (501 µM) cells, indicating iAs(III) uptake inhibition by extracellular phosphate. This conclusion was supported by the hyperbolic reduction in iAs(III) uptake rate (V) from 9.2 to 0.8 µmol/g-dw/h when the extracellular phosphate concentration went up from 0 to 250 µM. The maximal iAs(III) uptake rate (Vmax) of the -N alga (24.3 µmol/g-dw/h) was twice as much as that of the +NP (12 µmol/g-dw/h) and -P (8.1 µmol/g-dw/h) cells. It implies that more arsenic transporters were synthesized under the -N condition. Once accumulated, iAs(III) was oxidized and a higher proportion of arsenate (iAs(V)) was observed at lower [As]dis or under nutrient-limited conditions. Nevertheless, iAs(III) oxidation mainly occurred outside the cells with the extent of oxidation reciprocal to [As]dis. Based on the logistic modeling of the concentration-response curves in the +NP, -P, and -N toxicity tests, iAs(III) had an [As]dis-based EC50 of 1763, 13.1, and 1208 µM and an intracellular arsenic concentration based EC50 of 35.6, 28.8, and 195 µmol/g-dw, respectively. Higher iAs(III) toxicity to the -P cells occured because of their increased iAs(III) accumulation, whereas the underlying mechanisms why the -N alga was more tolerant need to be further revealed. Overall, both N and P had remarkable effects on the behavior and effects of iAs(III), which cannot be disregarded in the biogeochemical cycling research of arsenic.

Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin.

Melanin is the one of most important pigments for skin color in mammals. Excessive biosynthesis of melanin induces various pigment disorders. Much effort has been made to develop regulators to minimize skin pigmentation abnormalities. However, only a few of them are used, primarily because of safety concerns and low efficiency. In this study, we aimed to construct a novel nanosphere-gel for sequential delivery of salidroside and paeonol, to investigate the synergistic effects of these drugs in anti-melanogenesis, and to decrease their potential for toxicity in high dosage. Nanospheres were prepared and characterized for their particle size, polydispersity index, zeta potential, and morphological properties. The optimized nanospheres were incorporated in carbomer hydrogel with both paeonol and salidroside entrapped to form a dual drug-releasing nanosphere-gel. With this nanosphere-gel, rapid release of salidroside from the hydrogel followed by sustained release of paeonol from the nanosphere was achieved. Using a classical model of the melanogenesis response to ultraviolet exposure, it was shown that the anti-melanogenesis effects of the dual drug-releasing system, in which the doses of the individual drugs were decreased by half, was obviously enhanced when compared with the effects of the single drug preparations. Mechanistically, the burst release of salidroside from the hydrogel may enable prompt suppression of melanocyte proliferation on exposure to ultraviolet B radiation, while the paeonol released in a sustained manner can provide continuous inhibition of tyrosinase activity in melanocytes. Combined delivery of salidroside and paeonol was demonstrated to be a promising strategy for enhancing the therapeutic efficacy of these agents in anti-melanogenesis and reducing their toxicity, so may have great potential in nanomedicine.

Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin.

Salidroside, the major active component of Rhodiola rosea, a herb with antioxidant, free radical scavenging and tyrosinase inhibitory effects, has been recently reported in protecting the kerationcytes from the UV radiation, suggesting the potential of this component in depigmentation. Paeonol is isolated from Moutan Cortex Radicis with anti-inflammation/microbial activities, was reported to induce the down-regulation of microphthalmia-associated transcription factor and subsequently tyrosinase. To testify the potential of these compounds as melanin formation inhibitors for hyperpigmentation therapy, the influence of salidroside and paeonol on pigmentation was investigated. With arbutin as a positive control, salidroside and paeonol were evaluated for their inhibitory effect on the cell viability, tyrosinase activity and melanin synthesis in B16F10 melanoma cells, as well as their effects in UVB-induced hyperpigmentation in brown guinea pig skins. It was demonstrated that the significant inhibition of salidroside (33.0%) and paeonol (22.2-30.9%) on the tyrosinase activity is slightly lower than that of arbutin (18.4-44.7%). However, salidroside exhibited the dose-dependent inhibition (30.6-42.0%) in melanin synthesis at a low concentration of 100 µM, paeonol and arbutin expressed inhibition rates of 27.4-37.2% and 25.8-45.6% within 500-1000 µM. The in vivo topical application of these compounds was demonstrated to obviously decrease the hyperpigmentation on UVB stimulated guinea pig skin. This study provided the original evidence for the salidroside and paeonol as therapeutic agents for pigmentation disorder and skin lightening, with further clinical investigation of these compounds in the field of depigmentation was suggested.

Determination of twenty pesticide residues in Viscum coloratum by gas chromatography using cloud-point extraction / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a gas chromatography method for simultaneous determination of organochlorine and pyrethroid pesticide residues in Viscum coloratum by cloud-point extraction (CPE).</p><p><b>METHOD</b>Pesticides were extracted with the non-ionic surfactant Triton X-100. The apparatus was gas chromatography with electron capture detector and the separation was performed on an Hp-5 column. The pesticide residues were calculated by external standard method.</p><p><b>RESULT</b>Good linear relation was obtained over the range of 5-500 microg L(-1) for organochlorine and 10-1,000 microg L(-1) for pyrethroid. The limits of detection was 1.5-7.5 microg kg(-1). The average recoveries of organochlorine and pyrethroid were 74.15% -111.6% with corresponding RSD of 4.0% -9.1%.</p><p><b>CONCLUSION</b>The sample and rapid method was applied to pesticide residues determination.</p>