Evaluation of Renal Impairment in Patients with Diabetic Kidney Disease by Integrated Chinese and Western Medicine.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS: Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).

Overcoming Hypoxia-Induced Ferroptosis Resistance via a 19 F/1 H-MRI Traceable Core-Shell Nanostructure.

Lipid peroxides accumulation induced ferroptosis is an effective cell death pathway for cancer therapy. However, the hypoxic condition of tumor microenvironment significantly suppresses the efficacy of ferroptosis. Here, we design a novel nanoplatform to overcome hypoxia-induced ferroptosis resistance. Specifically, we synthesize a novel kind of perfluorocarbon (PFOB)@manganese oxide (MnOx) core-shell nanoparticles (PM-CS NPs). Owing to the good carrier of O2 as fuel, PM-CS NPs can induce higher level of ROS generation, lipid peroxidation and GSH depletion, as well as lower activity of GPX4, compared with MnOx NPs alone. Moreover, the supplement of O2 can relieve tumor hypoxia to break down the storage of intracellular lipid droplets and increase expression of ACSL4 (a symbol for ferroptosis sensitivity). Furthermore, upon stimulus of GSH or acidity, PM-CS NPs exhibit the "turn on" 19 F-MRI signal and activatable T1 /T2 -MRI contrast for correlating with the release of Mn. Finally, PM-CS NPs exert high cancer inhibition rate for ferroptosis based therapy via synergetic combination of O2 -mediated enhancement of key pathways of ferroptosis.

Integration of Artificial Intelligence, Blockchain, and Wearable Technology for Chronic Disease Management: A New Paradigm in Smart Healthcare.

Chronic diseases are a growing concern worldwide, with nearly 25% of adults suffering from one or more chronic health conditions, thus placing a heavy burden on individuals, families, and healthcare systems. With the advent of the "Smart Healthcare" era, a series of cutting-edge technologies has brought new experiences to the management of chronic diseases. Among them, smart wearable technology not only helps people pursue a healthier lifestyle but also provides a continuous flow of healthcare data for disease diagnosis and treatment by actively recording physiological parameters and tracking the metabolic state. However, how to organize and analyze the data to achieve the ultimate goal of improving chronic disease management, in terms of quality of life, patient outcomes, and privacy protection, is an urgent issue that needs to be addressed. Artificial intelligence (AI) can provide intelligent suggestions by analyzing a patient's physiological data from wearable devices for the diagnosis and treatment of diseases. In addition, blockchain can improve healthcare services by authorizing decentralized data sharing, protecting the privacy of users, providing data empowerment, and ensuring the reliability of data management. Integrating AI, blockchain, and wearable technology could optimize the existing chronic disease management models, with a shift from a hospital-centered model to a patient-centered one. In this paper, we conceptually demonstrate a patient-centric technical framework based on AI, blockchain, and wearable technology and further explore the application of these integrated technologies in chronic disease management. Finally, the shortcomings of this new paradigm and future research directions are also discussed.

Dietary Supplementation with Exogenous Sea-Cucumber-Derived Ceramides and Glucosylceramides Alleviates Insulin Resistance in High-Fructose-Diet-Fed Rats by Upregulating the IRS/PI3K/Akt Signaling Pathway.

Endogenous ceramide is considered to be associated with the progress of insulin resistance. However, the effects of dietary exogenous glucosylceramides and ceramides on insulin resistance are unclear. A model of fructose-induced male Sprague Dawley rats was used to compare the effects of sea-cucumber-derived glucosylceramides and ceramides on insulin resistance. Both glucosylceramides and ceramides significantly improved glucose tolerance, reduced the concentrations of serum glucose and glycosylated hemoglobin, and alleviated the accompanied hypertension. Ceramides significantly enhanced glycogen levels in skeletal muscle, whereas glucosylceramides significantly increased the hepatic glycogen levels. Moreover, glucosylceramides alleviated insulin resistance by inhibiting gluconeogenesis, promoting glycogen synthesis and insulin signal transduction in the liver; meanwhile, ceramides were mainly due to the promotion of glycogen synthesis and insulin signal transduction in skeletal muscle. Additionally, glucosylceramides and ceramides effectively attenuated inflammation in adipose tissue. These results indicate that glucosylceramides and ceramides have potential value in the prevention and alleviation of insulin resistance.

[Soil phosphorus forms and phosphorus solubilizing bacteria distribution after restoration from seriously burning in Greater Khingan Mountain areas, China]. / å¤§å ´å®‰å²­é‡åº¦ç«çƒ§è¿¹åœ°æ¢å¤åŽåœŸå£¤ç£·å½¢æ€ä¸Žè§£ç£·ç»†èŒåˆ†å¸ƒç‰¹å¾.

To understand the contents of various phosphorus forms, phosphorus solubilizing bacte-rial community structure and the relationship between them in soils after restoration from the seriously burning, we collected soil samples from artificial restoration (Pinus sylvestris var. mongolica plantation, Larix gmelinii plantation), artificial accelerated natural restoration (secondary forest) and natural restoration (natural secondary forest) stands in Greater Khingan Mountain area. Using methods of Sui et al. modified from Hedley phosphorus fractionation, we measured the contents of different phosphorus forms in rhizosphere soil and bulk soil (0-10, 10-20 cm). Abundances of phosphorus solubilizing bacteria were quantified by high-throughput sequencing method. The results showed that the contents of H2O-Pi, NaHCO3-Pi and NaHCO3-Poin 0-10 cm bulk soil and NaHCO3-Po in rhizosphere soil followed the order of L. gmelinii plantation : P. sylvestris var. mongolica plantation : natural secondary forest : secondary forest. The contents of H2O-Pi, NaHCO3-Pi, NaHCO3-Po in 10-20 cm bulk soil and H2O-Pi, NaHCO3-Pi in rhizosphere soil followed the order of L. gmelinii plantation : P. sylvestris var. mongolica plantation : secondary forest : natural secondary forest. The ratios of contents of H2O-Pi, NaHCO3-Pi and NaHCO3-Po in rhizosphere to those in bulk soil (R/S) were higher than 1 in all forest stands. The moderately labile NaOH-P included NaOH-Pi and NaOH-Po. The content of NaOH-P was in order of L. gmelinii plantation : natural secondary forest : secondary forest : P. sylvestris var. mongolica plantation in 0-10 cm layer of bulk and rhizosphere soil, and ranked as L. gmelinii plantation : P. sylvestris var. mongolica plantation : secondary forest : natural secondary forest in 10-20 cm layer of bulk soil. There was rhizosphere effect of NaOH-P in the soil. The stable HCl-P included HCl-Pi and HCl-Po. The content of HCl-P followed the order of L. gmelinii plantation : natural secondary forest : P. sylvestris var. mongolica plantation : secondary forest in 0-10 cm layer of bulk soil,and ranked as L. gmelinii plantation : P. sylvestris var. mongolica plantation : natural secondary forest : secondary forest in the 10-20 cm layer. The content of residual-P in the soil was not sensitive to restoration methods. Bradyrhizobium, Streptomyces, Burkholderia and Bacillus were the main phosphorus solubilizing bacteria across all forest stands. The abundances of phosphorus solubilizing bacteria in soil of L. gmelinii plantation and P. sylvestris var. mongolica plantation were significantly higher than that of secondary forest and natural secondary forest. Results of redundancy analysis showed that the correlation between phosphorus solubilizing bacteria and various phosphorus forms was different. Our results showed that artificial afforestation was more conducive in improving the availability of phosphorus in soil and the abundance of phosphorus solubilizing bacteria.

Structure and immunostimulating activity of a galactofuranose-rich polysaccharide from the bamboo parasite medicinal fungus Shiraia bambusicola.

ETHNOPHARMACOLOGICAL RELEVANCE: Shiraia bambusicola is a parasitic fungus on the twigs of bamboos. Its relatively large stroma has high medicinal value and can treat a variety of diseases such as rheumatoid arthritis, cold stomach pain, sciatica, injuries, chronic bronchitis, and infantile. It is widely distributed in many provinces in Southern China and also is also found in Japan. AIM OF THE STUDY: Medicinal fungi were important resources for bioactive polysaccharides. To explore bioactive polysaccharides from Shiraia bambusicola, a heteropolysaccharide SB2-1 was purified and obtained from S. bambusicola and its immunostimulating activity was researched. MATERIALS AND METHODS: The polysaccharide from S. bambusicola was extracted and purified using enzyme assisted extraction, ethanol precipitation, anion-exchange and size-exclusion chromatography. Molecular weight of polysaccharide was estimated by high performance gel permeation chromatography. Monosaccharide compositions were determined by high performance liquid chromatography after pre-column derivatization and UV detection. Structure information was elucidated by IR spectrum, GC-MS analysis after methylation and gradual acid hydrolysis of the polysaccharide. The RAW264.7 cells were used to study the immunostimulating activity in vitro. RESULTS: Physicochemical and structural analyses showed that SB2-1 was a neutral heteropolysaccharide with molecular weight at 22.2 kDa and consisted of glucose, galactose and mannose at a ratio of 2.0:1.5:1.0. The structure of SB2-1 was a branched polysaccharides composed of a mannan core and side chains consisted of glucose and galactose. The mannan core was composed of (1→2)-Manp as the main chain. Glucose with (1→4)-D-Glcp, (1→2)-D-Glcp and (1→6)-D-Glcp at different degrees of polymerization were linked at C-6 and C-3 of the (1→2)-Manp as the side chains. The galactose with the linages of (1→6)-D-Galf, →2)-D-Galf(1→ and terminal D-Galf(1→ also existed in the side chain. The study on the immunostimulating activities of SB2-1 and its core structure P-2 were investigated on RAW264.7 macrophages. The results showed that SB2-1 could activate RAW264.7 macrophage and significantly improve its phagocytic ability by neutral red uptake experiment. Meanwhile, SB2-1 increased significantly higher inducible nitric oxide synthase (iNOS) production and the productions of IL-1, IL-6, IL-12 and TNF-α. The effect of SB2-1 was better than its core structure P-2 produced by gradual acid hydrolysis, which meant the side chains played an important role in the immunostimulating activities. CONCLUSIONS: The investigation demonstrated that the galactofuranose-containing mannogalactoglucan was characteristic polysaccharides in S. bambusicola and could enhance the activation of macrophages.

Authentication of Processed Epimedii folium by EA-IRMS.

Processing of crude drug is a key character of traditional Chinese medicine (TCM), which could enhance the efficacy and/or reduce the toxicity of crude drugs to fulfill different requirements of TCM clinical practice. Epimedii folium (EF) is a widely used TCM. As a traditional method of TCM, EF is processed with refined mutton fat before being used in clinical practice. It has been reported that processing EF with mutton fat could improve the bioavailability and intestinal absorption of epimedium flavonoids and thus enhances the pharmacological effects. For economic benefits, it is possible to adulterate processed EF with unprocessed drug or process EF with cheaper plant oils. In the present study, 17 batches of crude and processed EF samples were collected from the Chinese market and 10 batches of replica processed drugs were prepared with different edible plant oils and animal fats in our laboratory. Elemental analyzer coupled with isotopic ratio mass spectrometry (EA-IRMS) was applied to determine the δ 13C values of the cyclohexane extracts of those samples. Significant differences could be observed in the results. EA-IRMS could be used to discriminate raw EF, processed EF, and EF processed with C3 plant oils.

Bioactive Exopolysaccharides Reveal Camellia oleifera Infected by the Fungus Exobasidium gracile Could Have a Functional Use.

Camellia oleifera is an important Chinese commercial crop. Camellia oleifera can display abnormal leaves due to infection by the parasitic fungus Exobasidium gracile. Exobasidium gracile was isolated from infected leaves and used in fermentation, and exopolysaccharides EP0-1 and EP0.5-1 were purified from the fermentation broth. EP0-1 was an alkaline polysaccharide consisting mainly of the linkages α-d-Manp(1→, →2)-α-d-Manp(1→ and →6)-α-d-Manp(1→, →3)-α-d-Glcp(1→ and→4)-α-d-Glcp(1→, terminal ß-d-Galf, (1→5)-ß-d-Galf, and terminal ß-D-GlcN(1→. EP0.5-1 was an acidic galactofuranose-containing polysaccharide. It contained the linkages of α-d-Manp(1→, →2)-α-d-Manp(1→, →6)-α-d-Manp(1→,→2, 6)-α-d-Manp(1→, →4)-α-d-Glcp(1→, and →4)-α-d-GlcUA(1→. Galactofuranose linkages were composed of terminal ß-d-Galf, (1→6)-ß-d-Galf and (1→2)-ß-d-Galf. Exobasidium gracile exopolysaccharides displayed significant immunoregulatory activity by activating macrophages. This research indicates that infected leaves from Camellia oleifera including the exopolysaccharides produced by the parasitic fungus Exobasidium gracile by are worth further investigation as a functional product.

Effect of Electroacupuncture in "Zusanli" and "Kunlun" Acupoints on TLR4 Signaling Pathway of Adjuvant Arthritis Rats.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. Previous study suggested that toll-like receptor (TLR) signaling pathway contributes to the development and progression of RA. In recent years, acupuncture has become one of the most vital treatments of arthralgia. But little is known about the mechanisms of improving RA by acupuncture. STUDY QUESTION: The study studied the effect of electroacupuncture in "Zusanli" and "Kunlun" acupoints on the expression of TLR4, myeloid differentiation factor 88 (MYD88), and NF-κB in adjuvant arthritis rats to clarify the molecular mechanism of acupuncture of RA. STUDY DESIGN: A rat model of adjuvant arthritis was established with injection of 0.1 mL Freund complete adjuvant in the right hindlimb footpad. We next punctured the Zusanli and Kunlun acupoints with 0.25 × 40-mm acupuncture needles to 5-mm depth. Then, we performed electroacupuncture treatment for 28 days with frequency of 2 Hz and intensity of 2 mA, once a day and 30 minutes each time. MEASURES AND OUTCOMES: Arthritis index and paw swelling were measured every week. FQ-PCR and western blot were used to detect the expression of TLR4, MYD88, and NF-κB. RESULTS: Paw swelling of rats injected with Freund complete adjuvant was more serious than that of the normal rats, which illustrated the successful establishment of adjuvant arthritis rat model. After treatment for 14 days, the paw swelling and joint symptoms score decreased, paw tissue inflammation eased in the rats of treatment group compared with the model group during the same period. After treatment for 28 days, the expression of TLR4, MYD88, and NF-κB in the ankle bone tissues decreased at both mRNA and protein levels. CONCLUSIONS: Stimulation with electric needle in Zusanli and Kunlun acupoints can reduce the expression of TLR4, MYD88, and NF-κB, which play an important role in treatment of adjuvant arthritis.

Comparison of neuroprotective effect of Forsythia suspensa leaf extract and forsythiaside, one of its metabolites.

As one of authentic Chinese medicinal materials in Shanxi Province, leaves of Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese) have been used as alternative for the relief or treatment of inflammation. The study aimed to compare the neuroprotective effects of extract from F. suspensa leaves and forsythiaside against inflammation and apoptosis induced by lipopolysaccharide (LPS) on hippocampal slices. The cultured hippocampal slices were treated with extract (5 and 50 µg/mL) and forsythiaside (5 and 50 µg/mL), respectively, followed by LPS treatment for 24 h. The present study showed that 60% ethanol extract of F. suspensa leaves exhibited better neuroprotective effect than equivalent forsythiaside.

Synchrotron radiation micro-CT as a novel tool to evaluate the effect of agomir-210 in a rat spinal cord injury model.

MicroRNA-210 (miR-210) was initially reported to be associated with hypoxia and plays a vital role in modulating angiogenesis. However, the potential effect and underlying mechanisms of miR-210 activity in rat spinal cord injury (SCI) have not yet been fully illuminated. In the present study, differential microRNA expression after SCI was determined by Microarray analysis. To explore the effect of miR-210 after SCI, we intrathecally injected agomir-210 with Alzet Osmotic Pumps to up-regulated the endogenous miR-210 expression. Then, synchrotron radiation micro-CT (SRµCT) imaging was used to investigate the effect of agomir-210 in rat SCI model. We found that the endogenous miR-210 expression could be up-regulated by intrathecal agomir-210 injection. The administration of agomir-210 significantly promoted angiogenesis, as evidenced by increased vessel number and volume detected by SRµCT, attenuated the lesion size and improved functional recovery after SCI. Additionally, agomir-210 attenuated cellular apoptosis and inflammation in the injured rat spinal cord. Expression levels of pro-apoptotic protein (Bax) and pro-inflammatory cytokines (TNF-α and IL-1ß) were significantly decreased after agomir-210 treatment, whereas expression levels of anti-apoptotic (Bcl-2) and anti-inflammatory (IL-10) proteins were up-regulated. In conclusion, our results indicated that SRµCT is a powerful imaging tool to evaluate the effects of angiogenesis after agomir-210 administration in rat SCI model. The up-regulation of endogenous miR-210 expression following agomir-210 administration promoted angiogenesis and anti-apoptotic protein expression, and attenuated inflammation. MiR-210 played a positive role in neurological functional recovery and could be a potential new therapeutic target for SCI.

Effects of Xuebijing injection on microcirculation in septic shock.

BACKGROUND: This study was conducted to investigate whether Xuebijing injection can rectify the dysfunction of microcirculation in septic shock and assessed the microcirculatory parameters directly via orthogonal polarization spectral and software AVA 3.0. MATERIAL AND METHODS: Anesthetized and mechanically ventilated beagle dogs were modeled for septic shock via lipopolysaccharide (LPS) intravenous injection. They were divided randomly into four groups, control group accepted operation only for jejunostomy and cystostomy; LPS group accepted operation and LPS intravenous injection; saline group accepted operation, LPS intravenous injection, and saline resuscitation; XBJ group accepted operation, LPS intravenous injection, saline resuscitation, and Xuebijing injection infusion. The MAP was recorded via right femoral artery catheterization, at the same time, the blood gas analysis was taken via that pathway at the set time points. ScvO2 was obtained via right jugular vein catheterization at the related time points. Microcirculatory parameters were recorded by orthogonal polarization spectral via the jejunum stoma, and the microcirculation image was analyzed via the software AVA 3.0 later. RESULTS: Xuebijing injection improved microcirculation of the jejunum villus in canine model of septic shock induced by endotoxin, especially for the proportion of perfused vessels. CONCLUSIONS: Based on the adequate fluid resuscitation, Xuebijing injection plays a helpful role of improving microcirculation in septic shock.

Heparin inhibits lipopolysaccharide-induced inflammation via inducing caveolin-1 and activating the p38/mitogen-activated protein kinase pathway in murine peritoneal macrophages.

Heparin is a soluble glycosaminoglycan largely used as an anti-coagulant drug and with well known anti­inflammatory effects. However, heparin is currently not used as an anti­inflammatory agent in the clinic due to a risk of bleeding as well as its complex mechanism of action. The underlying mechanism of the anti­inflammatory action of heparin and its effector targets have remained to be fully elucidated. The present study confirmed the anti­inflammatory effects of heparin in lipopolysaccharide (LPS)­induced murine peritoneal macrophages through decreasing the levels of the inflammatory cytokines tumor necrosis factor alpha (TNF­α), interleukin 6 (IL­6), IL­8 and IL­1ß. Caveolin­1 participated in the anti­inflammatory process and it was able to be induced by heparin. Transfection of small interfering RNA of caveolin­1 into murine peritoneal macrophages attenuated the anti­inflammatory effects of heparin. Furthermore, following caveolin­1 silencing, the p38/mitogen­activated protein kinase (MAPK) pathway was still able to be activated by heparin, while the extracellular signal­regulated kinase and c­Jun N­terminal kinase pathways were inhibited. In conclusion, these results suggested that heparin inhibits LPS­induced inflammation via inducing caveolin­1 and activating the p38/MAPK pathway in murine peritoneal macrophages. Revealing the anti­inflammatory mechanisms of heparin will aid in its development for clinical treatment in the future.

Crocetin downregulates the proinflammatory cytokines in methylcholanthrene-induced rodent tumor model and inhibits COX-2 expression in cervical cancer cells.

The effect of crocetin (C20H24O4) on methylcholanthrene- (MCA-) induced uterine cervical cancer in mice was studied in this paper. After the mice were treated orally with crocetin, maleic dialdehyde (MDA), polymorphonuclear cells (PMN), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were examined by ELISA or immunohistochemistry. The inducible nitric oxide synthase (iNOS) activation in HeLa cells was analyzed using fluorescence microscopy for light microscopic examination. The MCA mice showed a significant increase in plasma MDA, PMN, IL-1ß, TNF-α, and nitrates levels. At the same time, the mRNA level of COX-2 in HeLa cells was also significantly increased. These changes were attenuated by crocetin supplementation in the MCA mice. Crocetin supplementation in the MCA mice also showed protection against cervical cancer. These results suggest that crocetin may act as a chemopreventive and an anti-inflammatory agent.

Ortho vs ipso: site-selective Pd and norbornene-catalyzed arene C-H amination using aryl halides.

A Pd and norbornene-catalyzed ortho-arene amination via Catellani-type C-H functionalization is reported. Aryl halides are used as substrates; N-benzoyloxyamines and isopropanol are employed as the amine source (oxidant) and reductant respectively. Examples are provided in 50-99% yields with high functional group tolerance. This method gives complementary site selectivity at the ortho- instead of ipso-position of aryl halides.

Application of a rapid and efficient quantitative analysis method for traditional Chinese medicines: the case study of quality assessment of Salvia miltiorrhiza Bunge.

A reference extractive, containing multiple active known compounds, has been considered to be an alternative to individual reference standards. However, in the Chinese Pharmacopoeia (ChP) the great majority of reference extractives have been primarily used for qualitative identification by thin-layer chromatography (TLC) and few studies on the applicability of reference extractives for quantitative analysis have been presented. Using Salvia miltiorrhiza Bunge as an example in this paper, we first present a preliminary discussion on the feasibility and applicability of reference extractives for the quantitative analysis of TCMs. The reference extractive of S. miltiorrhiza Bunge, comprised of three pharmacological marker compounds, namely cryptotanshinone, tanshinone I and tanshinone IIA, was prepared from purchased Salvia miltiorrhiza Bunge by extraction with acetone under reflux, followed by silica gel column chromatography with stepwise elution with petroleum ether-ethyl acetate (25:1, v/v, 4.5 BV) to remove the non-target components and chloroform-methanol (10:1, v/v; 3 BV) to yield a crude reference extractive solution. After concentration, the solution was further purified by preparative reversed-phase HPLC on a C18 column with isocratic elution with 77% methanol aqueous solution to yield the total reference extractive of S. miltiorrhiza Bunge. Thereafter, the reference extractive was applied to the quality assessment of S. miltiorrhiza Bunge using high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD). The validation of the method, including linearity, sensitivity, repeatability, stability and recovery testing, indicated that this method was valid, reliable and sensitive, with good reproducibility. The developed method was successfully applied to quantify seven batches of samples collected from different regions in China and the results were also similar to those obtained using reference standards, with relative standard deviation (RSD) <3%. Preparation of a reference extractive of S. miltiorrhiza Bunge was significantly less expensive and time consuming than preparation of a corresponding reference standard. Quantitative analysis using a reference extractive was shown to be simple, low-cost, time-saving and practical, with high sensitivity and good stability; and is, therefore, a strong alternative to the use of reference standards.

Effects of HMG-CoA reductase inhibitor on experimental autoimmune myocarditis.

PURPOSE: Myocarditis is an acute inflammatory disease of the heart and is often a precursor of dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) has been used as a model for human myocarditis. The purpose of this study was to investigate the therapeutic role of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitor, rosuvastatin, on the development of EAM. METHODS: Experimental autoimmune myocarditis was induced in BALB/c mice by immunization with murine cardiac α-myosin heavy chain (MyHc-α(614-629) [Ac-SLKLMATLFSTYASAD-OH]). High-dose (10 mg/kg/day) or low-dose (1 mg/kg/day) rosuvastatin or vehicle was administered orally by gastric gavage to mice with EAM from day 0 to day 21 after immunization. On day 21 after immunization, echocardiography was carried out and the severity of myocarditis was detected by histopathological evaluation. Levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured by ELISA. Histopathology was performed using haematoxylin and eosin. With apoptosis examined by Tunel, the expression of active caspase-3 in myocardium was investigated by immunohistochemistry. RESULTS: Rosuvastatin attenuated the histopathological severity of myocarditis. Cardiac function was improved in the two rosuvastatin-treated groups compared to the non-treated EAM group (LVFS: high-dose rosuvastatin group [group H], 0.38 ± 0.10%; low-dose rosuvastatin group [group L], 0.34 ± 0.06%; non-treated EAM group [group N], 0.29 ± 0.07%. LVEF: group H, 0.80 ± 0.09%; group L, 0.71 ± 0.07%; group N, 0.68 ± 0.07%). Furthermore, treatment with rosuvastatin decreased the expression levels of TNF-α (group H, 65.19 ± 7.06 pg/ml; group L, 108.20 ± 5.28 pg/ml; group N, 239.34 ± 11.65 pg/ml) and IL-6 (group H, 14.33 ± 2.15 pg/ml; group L, 19.67 ± 3.04 pg/ml; group N, 40.39 ± 7.17 pg/ml). The rates of expression of active Caspase-3 and myocardial apoptosis were positively correlated with the scores for myocardial pathology. CONCLUSIONS: These results demonstrate that administration of rosuvastatin can ameliorate EAM progression, inhibit apoptosis of cardiomyocytes, and preserve cardiac output, and they also suggest rosuvastatin may be a promising novel therapeutic strategy for the clinical treatment of myocarditis.

[Optimization of processing technologies for dipsaci radix habitat by comprehensive evaluation method].

OBJECTIVE: To optimize the processing technologies of Dipsaci Radix by comprehensive method. METHODS: According to the Chinese Pharmacopoeia (2010 edition), UV Spectrophotometry and HPLC analysis were used to determine the contents of total saponins, saponins VI of water extract and alcohol extract of Dipsaci Radix. Comprehensive evaluation method was used to optimize the processing technologies for Dipsaci Radix habitat. RESULTS: The sequence of quality of processing was as follows: baked half dry sweating products (0.7046) > half dry sweating products (0.5857) in the shade > scald soft sweating products (0.5852) > bask dried products (0.3138) > evaporate soft sweating products (0.0952). CONCLUSION: The processing technology optimized by the comprehensive method can ensure the quality of Dipsaci Radix.

Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-uronamides as highly potent and selective agonists at the human A3 adenosine receptor.

We have established structure-activity relationships of novel 4'-thionucleoside analogues as the A(3) adenosine receptor (AR) agonists. Binding affinity, selectivity toward other AR subtypes, and efficacy in inhibition of adenylate cyclase were studied. From this study, 2-chloro-N(6)-methyl-4'-thioadenosine-5'-methyluronamide (36a) emerged as the most potent and selective agonist at the human A(3) AR. We have also revealed that, similar to 4'-oxoadenosine analogues, at least one hydrogen on the 5'-uronamide moiety was necessary for high-affinity binding at the human A(3) AR, presumably to allow this group to donate a H bond within the binding site. Furthermore, bulky substituents on the 5'-uronamide reduced binding affinity, but in some cases large 5'-uronamide substituents, such as substituted benzyl and 2-phenylethyl groups, maintained moderate affinity with reduced efficacy, leading to A(3) AR partial agonists or antagonists. In several cases for which the corresponding 4'-oxonucleosides have been studied, the 4'-thionucleosides showed higher binding affinity to the A(3) AR.

[Effects of fraction from Phyllanthus urinaria on thrombosis and coagulation system in animals].

OBJECTIVE: To investigate the effects of PUW (a fraction containing 60% corilagin from a Chinese herbal plant Phyllanthus urinaria) on thrombosis and coagulation system. METHODS: Myers's method was used to evaluate the protection of intravenously administered PUW against the male mouse sudden death caused by injection of 75 mg/kg arachidonic acid in the tail vein; Charlton's method was modified to observe antithrombotic effect of PUW in rat electrically stimulated carotid artery thrombosis model; and the model of venous thrombosis was produced to investigate the antithrombotic effect of PUW. Rosette assay was used to observe the effect of PUW on platelet-neutrophil adhesion. The effects of PUW were monitored on euglobulin lysis time (ELT), prothrombin time (PT), kaolin partial thromboplastin time (KPTT), and bleeding time (BT) in rats, according to the methods of Kowalski, HUANG Zheng-Liang, and GU Yue-Fang, et al, respectively. RESULTS: The results showed that PUW administered intravenously significantly decreased the mouse mortality, prolonged the occlusion time of rat carotid arteries, and reduced the wet and dry thrombus weight of the inferior vena cava, respectively. PUW markedly inhibited the binding of activated platelets to neutrophils, obtaining 39.7 mg/L of the medium inhibitory concentration. Intravenously administered PUW significantly shortened ELT, prolonged KPTT while had no influence on PT; PUW increased BT in rat tail tips but the BT caused by PUW was much shorter than that by aspirin or urokinase. CONCLUSION: It is suggested that PUW has the potential of antithrombosis due to its inhibition of platelet-neutrophil adhesion. PUW shows the tendency to bleeding, however, it could not cause serious bleeding side effect as compared with aspirin or urokinase.