Viola yedoensis Makino formula alleviates DNCB-induced atopic dermatitis by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.

BACKGROUND: Atopic dermatitis (AD), a common inflammatory skin disorder, severely affects the life quality of patients and renders heavy financial burden on patient's family. The Chinese medicine Viola yedoensis Makino formula (VYAC) has been widely used for treating various skin disorders. Previous studies have reported that VYAC is effective in relieving DNCB-induced AD and inflammation. However, the anti-inflammatory mechanism of VYAC is still ill-defined and poorly understood. This study aims to investigate the therapeutic effects of VYAC on DNCB-induced AD and to elucidate the underlying anti-inflammatory mechanisms. METHODOLOGY: VYAC were extracted with 70% ethanol and lyophilized for use. AD mice were established by DNCB. The therapeutic effects of VYAC were evaluated by oral administration VYAC (150, 300 and 600 mg/kg) daily in vivo. The histopathological and immunohistochemistry were used to analyze skin lesion and macrophages infiltration, RT-qPCR and Elisa were used to analyze the inflammatory factors in skin tissues and serum. To explore the underlying mechanism of VYAC against AD in vitro. RAW264.7 cells and bone-marrow-derived macrophages (BMDMs) were employed for macrophage polarization analysis. Flow cytometer, immunofluorescence and western blot were used to analyze M2 macrophages markers. STAT3 siRNA were transfected into both cells to validate the effects of VYAC-induced macrophages M2 polarization via JAK2/STAT3 signaling pathway. RESULTS: VYAC ameliorated skin lesion of DNCB-induced AD mice by decreased clinical scores and epidermal thickness, decreased the level of pro-inflammatory factors (IL-1ß, TNF-α and IL-18) and enhanced IL-10 anti-inflammatory factor level, inhibited macrophages infiltration and promoted M2 macrophages polarization in vivo. VYAC significantly promoted M2 macrophages polarization in vitro. It is observed that VYAC not only inhibited the phosphorylation of JAK2 and STAT3 in RAW264.7 cells and BMDMs, but also accelerated the translocation to the nucleus. What's more, VYAC reduced the polarization of M2 macrophage by activating JAK2/STAT3 signaling pathway was observed in both cells. CONCLUSIONS: Our findings demonstrate that VYAC significantly ameliorates skin lesion of DNCB-induced AD mice and reduces the levels of inflammatory factors by activating JAK2/STAT3 signaling pathway and promoting M2 macrophages polarization.

Contrasting Responses of Multispatial Soil Fungal Communities of Thuja sutchuenensis Franch., an Extremely Endangered Conifer in Southwestern China.

Thuja sutchuenensis Franch. is an endangered species in southwest China, distributed sporadically in mountainous areas. Soil property and soil fungal community play a crucial role in plant growth and survival. Nevertheless, understanding soil properties and the soil fungal community in the areas where T. sutchuenensis is distributed is extremely limited. Hence, this study collected a total of 180 soil samples from five altitudinal distribution areas (altitudinal gradients) and three vertical depths throughout four horizontal distances from the base of each tree. The results found that altitudinal gradients and vertical depths altered soil properties, including pH, organic matter content, water content, total nitrogen, phosphorus, and potassium, and available nitrogen, phosphorus, and potassium. The fungal alpha diversity indexes (Chao1 and Shannon) and beta diversity were dramatically decreased with elevation. In addition, high altitudes (2,119 m) harbored the highest relative abundance of ectomycorrhizal fungi (27.57%) and the lowest relative abundance of plant-pathogenic fungi (1.81%). Meanwhile, we identified a series of fungal communities, such as Tomentella, Piloderma, Cortinarius, Sebacina, and Boletaceae, that play an essential role in the survival of T. sutchuenensis. The correlation analysis and random forest model identified that water content and total phosphorus showed strong relationships with fungal characteristics and were the primary variables for Zygomycota and Rozellomycota. Collectively, the findings of this integrated analysis provide profound insights into understanding the contrasting responses of T. sutchuenensis soil fungal communities and provide a theoretical basis for T. sutchuenensis habitat restoration and species conservation from multispatial perspectives. IMPORTANCE The present study highlights the importance of fungal communities in an endangered plant, T. sutchuenensis. Comparative analysis of soil samples in nearly all extant T. sutchuenensis populations identified that soil properties, especially soil nutrients, might play critical roles in the survival of T. sutchuenensis. Our findings prove that a series of fungal communities (e.g., Tomentella, Piloderma, and Cortinarius) could be key indicators for T. sutchuenensis survival. In addition, this is the first time that large-scale soil property and fungal community investigations have been carried out in southwest China, offering important values for exploring the distribution pattern of regional soil microorganisms. Collectively, our findings display a holistic picture of soil microbiome and environmental factors associated with T. sutchuenensis.

Developing long-term conservation priority planning for medicinal plants in China by combining conservation status with diversity hotspot analyses and climate change prediction.

BACKGROUND: Medicinal plants have always played an important role in the history of human health. However, the populations and sustainable use of medicinal plants have been severely affected by human activities and climate change. Little is known about the current conservation status and distribution pattern of medicinal plants. In this study, based on accurate geographical distribution information of 9756 medicinal plants, we identified diversity hotspots and conservation gaps, evaluated conservation effectiveness of nature reserves, and predicted suitable habitat areas for medicinal plants in China to provide scientific guidance for their long-term conservation and sustainable use. RESULTS: A total of 150 diversity hotspot grid cells, mainly concentrated in central and southern China, were identified. These only accounted for 5% of the total distribution area but contained 96% of the medicinal plants of the country. The hotspot grid cells included all traditional hotspot areas, but we also detected three new hotspots, namely Mufu-Lushan Mountains, Tianshan-Altai Mountains, and Changbai Mountains. The current national and provincial nature reserves protect 125 hotspot grid cells, which harbor 94% of all medicinal plants. However, 25 hotspot grid cells, distributed in the Tianshan-Altai Mountains and Hengduan Mountains, are located outside the national and provincial nature reserves. An analysis of the predicted effects of climate change indicated that the suitable habitat areas will shift from southern to northern China, and that southern China will face a considerable loss of suitable habitat areas, while the east and west parts of China will encompass remarkably more suitable habitat areas in the future. CONCLUSIONS: The current conservation networks have achieved high conservation effectiveness with regard to medicinal plants; however, the conservation gaps we identified should not be neglected, and conservation planning needs to take into account the predicted shifts of some hotspots of medicinal plants due to climate change.

Phosphorus transformation during the carbonaceous skeleton assisted thermal hydrolysis of sludge.

On the basis of the carbonaceous skeleton assisted thermal hydrolysis that we proposed to achieve efficient sludge dewatering, this work further explored phosphorus (P) transformation in the process. The results showed that during independent thermal hydrolysis in the temperature range of 120-240 °C, organic-P was first decomposed into soluble-P and particulate-P in liquid, and then combined with Ca, Fe, and Al to form more apatite-P (AP) and less non-apatite inorganic-P (NAIP). When the skeleton assisted the sludge thermal hydrolysis, the turning point of the hydrolysis temperature would reduce from 180 °C to 150 °C, at which the liquid-P began to decrease and the organic-P generally decomposed. Moreover, the increment in the content of AP halved while that of NAIP doubled compared to that in the process without the carbonaceous skeleton. These effects come from the exogenous components introduced by adding the skeleton, which were different from the sludge. Compared with the P-rich compound and metal elements that tend to bond with phosphate introduced by the skeleton, hemicellulose as a main organic component played a leading role in the different P transformations of AP and NAIP. The hemicellulose slightly increased the acidity of sludge products, thereby inhibiting AP production and promoting the production of recyclable NAIP. Overall, the carbonaceous skeleton assisted thermal hydrolysis was beneficial for P recovery with a very low filtrate loss rate.

Impact of administration route on nanocarrier biodistribution in a murine colitis model.

The incidence of inflammatory bowel disease (IBD) is increasing worldwide. Although current diagnostic and disease monitoring tests for IBD sensitively detect gut inflammation, they lack the molecular and cellular specificity of positron emission tomography (PET). In this proof-of-concept study, we use a radiolabeled macrophage-targeted nanocarrier probe (64Cu-NOTA-D500) administered by oral, enema, and intraperitoneal routes to evaluate the delivery route dependence of biodistribution across healthy and diseased tissues in a murine model of dextran sodium sulfate (DSS)-induced colitis. High inter-subject variability of probe uptake in intestinal tissue was reduced by normalization to uptake in liver or total intestines. Differences in normalized uptake between healthy and DSS colitis animal intestines were highest for oral and IP routes. Differences in absolute liver uptake reflected a possible secondary diagnostic metric of IBD pathology. These results should inform the preclinical development of inflammation-targeted contrast agents for IBD and related gut disorders to improve diagnostic accuracy.

The Role of the Gut Microbiota in Coronary Heart Disease.

PURPOSE OF REVIEW: This review focuses on recent evidence examining the role gut microbiota play in coronary heart disease. It also provides a succinct overview of current and future therapies targeting the gut microbiota for coronary heart disease risk reduction. RECENT FINDINGS: A consensus has been reached that differences exist in the gut microbiotas of patients with coronary heart disease. Studies have shown that the gut microbiota is associated with obesity, diabetes, dyslipidemia, and hypertension, which are risk factors for coronary heart disease. The gut microbiota is involved in mediating basic metabolic processes, such as cholesterol metabolism, uric acid metabolism, oxidative stress, and inflammatory reactions, through its metabolites, which can induce the development of atherosclerosis and coronary heart disease. Interfering with the composition of gut microbiota, supplementing probiotics, and fecal donation are active areas of research to potentially prevent and treat coronary heart disease. Gut microbiota are causally associated with coronary heart disease. We analyzed the gut microbiota's effects on risk factors for coronary heart disease and studied the effects of gut microbiota metabolites on coronary heart disease. Gut microbiota is a potential target for preventing and treating coronary heart disease.

[Karyotype and evolutionary trend analysis of Scutellaria species in Jinyun mountain, Chongqing].

Traditional squash method was used to analyze chromosome number and karyotypes of four Scutellaria species in Chongqing Jinyun Mountain Natural Reserve： Scutellaria tsinyunensis, S.yunnanensis, S.franchetiana and S.indica.The result showed that the chromosome numbers were 26 except for S.franchetiana, which had 24 chromosomes.These species were all diploid with metacentric and submetacentric chromosomes.Their karyotypes were symmetrical and primitive.The karyotype formula of S.tsinyunensis is 2n=2x=26=24m+2sm, 1B type, As.k=55.28%; the karyotype formula of S.yunnanensis var.salicifolia is 2n=2x=26=26m, 1B type, As.k=56.11%; the karyotype formula of S.franchetiana is 2n=2x=24=20m+4sm, 2B type, As.k=58.50%; the karyotype formula of S.indica is 2n=2x=24=20m+4sm, 2B type, As.k=58.41%.The results were compared with the reported data of S.baicalensis and S.alaschanica.S.alaschanica is expected to be the most advanced one whereas S.tsinyunensis, and S.yunnanensis var. salicifolia primitive.These results are expected to provide some references to the origin and differentiation of genus Scutellaria.

Effects of renal sympathetic denervation on the atrial electrophysiology in dogs with pacing-induced heart failure.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are associated with sympathetic activation. Renal sympathetic denervation (RSD) can suppress AF vulnerability. The impact of RSD on atrial electrophysiology in experimental HF is unclear. METHODS: Twenty-two beagles were randomized into control, HF, and HF + RSD groups. Control dogs were implanted cardiac pacemakers without pacing. Dogs in the HF group underwent right ventricular pacing for 3 weeks at 240 beats/min to induce HF. The dogs in the HF + RSD group received RSD and underwent the same HF-inducing procedure. RESULTS: The P-wave dispersion was higher in HF dogs than in the control and HF + RSD dogs (19 ± 3.1 ms vs 13 ± 2.3 ms, 15 ± 2.9 ms, P = 0.04). Conduction time within the interatrium was significantly longer in the HF dogs than that in the control and HF + RSD dogs (39 ± 4 ms vs 31 ± 3 ms, 33 ± 4 ms; P = 0.03). Window of vulnerability (WOV) of AF was widened in the HF dogs than in the HF + RSD dogs (37 ± 5 ms vs 14 ± 3 ms; P < 0.01), while AF could not be induced (WOV = 0) in the control dogs during S1 S2 stimulation. The voltage in the threshold for AF inducibility was lower during ganglionated plexi stimulation in the HF dogs than in the control and HF + RSD dogs (1.8 ± 0.6 V vs 2.5 ± 0.6 V, 2.4 ± 0.4 V; P = 0.04). CONCLUSIONS: RSD could reverse the atrial electrical remodeling and decrease AF inducibility in dogs with pacing-induced HF.

[Allelopathic effects of companion species on spore germination and gametophyte development in Cibotium barometz].

OBJECTIVE: To study the relationship between Cibotium barometz and its companion species, Arachniodes falcate and Alpinia japonica, we used aqueous leachates of the two companions to deal with C. barometz spores. METHOD: Spores of C. barometz were translated on MS culture which contained different concentration of aqueous extracts of the two companions, the germination and gametophyte development were observed and recorded. RESULT: All extracts inhibited and delayed the C. barometz spores germination and rhizoid elongation was inhibited. It also had obvious inhibition to the prothallus formation and sexual differentiation. And the higher concentration, the more obvious inhibition of aqueous extracts of the two companion species. CONCLUSION: The two companion species have allelopathic effects on the spore germination and gametophyte development of C. barometz. And it may have an influence on sporogon ontogenesis and the population expansion.

Inflammation abnormalities and inducibility of atrial fibrillation after epicardial ganglionated plexi ablation.

BACKGROUND: Epicardial ganglionated plexi (GP) ablation can prevent atrial fibrillation inducibility. However, the long-term effects of GP ablation on atrial fibrillation have not been elucidated. METHODS: Thirteen adult dogs of either sex, weighing 13-17kg, were randomly assigned to a sham-operated group (n=6) or a GP ablation group (n=7). After right thoracotomy, the atrial effective refractory period (AERP) was measured and atrial fibrillation was induced by right atrial rapid burst pacing. Atrial fibrillation and AERP were remeasured after anterior right and inferior right GP ablation in the GP ablation group. The animals were allowed to recover for 8 weeks, after which atrial fibrillation and AERP were measured again. Concentrations of C-reactive protein, tumour necrosis factor-alpha (TNF-α) and interleukin-6 were measured in the blood and atrial tissues. RESULTS: After 8 weeks, atrial fibrillation was induced in all animals in the GP ablation group. AERP and dispersion of AERP (dAERP; maximum AERP minus minimum AERP) were increased after GP ablation but AERP recovered after 8 weeks. There were no significant differences in the concentrations of C-reactive protein, TNF-α or interleukin-6 in venous blood between the two groups and the concentration of C-reactive protein in the atrium did not change before and after GP ablation. However, the concentrations of TNF-α and interleukin-6 in the atrium increased significantly 8 weeks after GP ablation (P<0.05). CONCLUSION: Increased concentrations of TNF-α and interleukin-6 in the atrium after GP ablation provide a new causative factor in terms of atrial fibrillation vulnerability.

[Analysis of fingerprint and bioactive components in different parts of Scutellaria tsinyunensis by HPLC].

OBJECTIVE: Used HPLC to set up fingerprint of medicinal-plant Scutellaria tsinyunensis collected from Jinyun mountain of Chongqing, and to determine four flavonoids in its root, stem and leaf. METHOD: Analysis was carried out on a COSMOSIL C18-PAQ column (4.6 mm x 250 mm, 5 microm) with acetonitrile and H2O-H3PO4-THF(85:12:0.3) as the mobile phases in a gradient elution, with a flow rate of 1.0 mL x min(-1). The column temperature was 30 TC, and the detection wavelength was 275 nm. The fingerprints of ten populations were determined, and the data were analyzed by the similarity evaluation software. RESULT: The mutual mode of HPLC fingerprint was established. There were 14 common peaks in all, each peak was well separated. The peak was steady and showed good repeatability. Compared with the mutual mode, the similarities of 10 samples were 0.987 0.994, 0.993, 0.971, 0.983, 0.994, 0.981, 0.981, 0.988, 0.972, and the average similarity was 0.984. The chromatographic profiles of 10 samples were very similar. The four flavonoids were determined successfully by this method. The results showed that the content of flavonoids in the root was the most, and the leaf was the least. CONCLUSION: This method was steady and reliable which could be applied in identification, genetic diversity analysis, protection and utilization of S. tsinyunensis.

[Observation on gametophyte development of Cibotium barometz].

OBJECTIVE: To observe the spores germinating process of Cibotium barometz, and understand the growth principle provided for experience for indoor culturing and further research. METHOD: The spores of C. barometz were cultured both in inorganic medium and in the soil from original habitat, and the whole process of spores germination and the development of gametophytic were observed under microscope. RESULT: The spores germinated about 1-2 weeks after being sowed, and the type of germination belonged to Vittaria-type. The prothallial plates formed in 25 days after being sowed, while hairs developed after the formation of the prothallial plate. The gametophyte formed about 40 days after being sowed. But the type of mature prothalli was cordate. The antheridia formed in 60 days after inoculation, while the archegonia developed in 10 days after the formation of antheridia. CONCLUSION: Soil based indoor culturing of C. barometz spores is practical and can be used for cultivation of C. barometz.