Natural Chlorogenic Acid Planted Nanohybrids with Steerable Hyperthermia for Osteosarcoma Suppression and Bone Regeneration.

Surgical resection is the most common approach for the treatment of osteosarcoma. However, two major complications, including residual tumor cells and large bone defects, often arise from the surgical resection of osteosarcoma. Discovering new strategies for programmatically solving the two above-mentioned puzzles has become a worldwide challenge. Herein, a novel one-step strategy is reported for natural phenolic acid planted nanohybrids with desired physicochemical properties and steerable photothermal effects for efficacious osteosarcoma suppression and bone healing. Nanohybrids are prepared based on the self-assembly of chlorogenic acid and gold nanorods through robust Au-catechol interface actions, featuring precise nanostructures, great water solubility, good stability, and adjustable hyperthermia generating capacity. As expected, on the one hand, these integrated nanohybrids can severely trigger apoptosis and suppress tumor growth with strong hyperthermia. On the other hand, with controllable mild NIR irradiation, the nanohybrids promote the expression of heat shock proteins and induce prominent osteogenic differentiation. This work initiates a brand-new strategy for assisting osteosarcoma surgical excision to resolve the blockage of residual tumor cells elimination and bone regeneration.

Aesculin suppresses the NLRP3 inflammasome-mediated pyroptosis via the Akt/GSK3ß/NF-κB pathway to mitigate myocardial ischemia/reperfusion injury.

BACKGROUND: Aesculin (AES), an effective component of Cortex fraxini, is a hydroxycoumarin glucoside that has diverse biological properties. The nucleotide-binding domain leucine-rich repeat-containing receptor, pyrin domain-containing 3 (NLRP3) inflammasome has been heavily interwoven with the development of myocardial ischemia/reperfusion injury (MIRI). Nevertheless, it remains unclear whether AES makes a difference to the changes of the NLRP3 inflammasome in MIRI. PURPOSE: We used rats that were subjected to MIRI and neonatal rat cardiomyocytes (NRCMs) that underwent oxygen-glucose deprivation/restoration (OGD/R) process to investigate what impacts AES exerts on MIRI and the NLRP3 inflammasome activation. METHODS: The establishment of MIRI model in rats was conducted using the left anterior descending coronary artery ligation for 0.5 h ischemia and then untying the knot for 4 h of reperfusion. After reperfusion, AES were administered intraperitoneally using 10 and 30 mg/kg doses. We evaluated the development of reperfusion ventricular arrhythmias, hemodynamic changes, infarct size, and the biomarkers in myocardial injury. The inflammatory mediators and pyroptosis were also assessed. AES at the concentrations of 1, 3, and 10 µM were imposed on the NRCMs immediately before the restoration process. We also determined the cell viability and cell death in the NRCMs exposed to OGD/R insult. Furthermore, we also analyzed the levels of proteins that affect the NLRP3 inflammasome activation, pyroptosis, and the AKT serine/threonine kinase (Akt)/glycogen synthase kinase 3 beta (GSK3ß)/nuclear factor-kappa B (NF-κB) signaling pathway via western blotting. RESULTS: We found that AES notably attenuated reperfusion arrhythmias and myocardia damage, improved the hemodynamic function, and ameliorated the inflammatory response and pyroptosis of cardiomyocytes in rats and NRCMs. Additionally, AES reduced the NLRP3 inflammasome activation in rats and NRCMs. AES also enhanced the phosphorylation of Akt and GSK3ß, while suppressing the phosphorylation of NF-κB. Moreover, the allosteric Akt inhibitor, MK-2206, abolished the AES-mediated cardioprotection and the NLRP3 inflammasome suppression. CONCLUSIONS: These findings indicate that AES effectively protected cardiomyocytes against MIRI by suppressing the NLRP3 inflammasome-mediated pyroptosis, which may relate to the upregulated Akt activation and disruption of the GSK3ß/NF-κB pathway.

[Guiding mechanism of platycodin D in treatment of mouse lung cancer with doxorubicin].

This study is to observe whether platycodin D has the guiding role in treatment of mouse lung cancer with doxorubicin and explore its guiding mechanism. In vitro, platycodin D and doxorubicin(alone or in combination) were added into Lewis lung cancer(LLC) cells to detect the cell proliferation and doxorubicin uptake. Cell morphological changes were analyzed by cell holographic analysis system; cell gap junctional intercellular communication(GJIC) was tested by fluorescent yellow tracer; lyso-tracker red was used to examine lysosomal function; LC-3 B(Light chain 3 beta)and P62(heat shock 90-like protein)staining were used to test auto-phagy and autophagic degradation respectively; and P-glycoprotein(P-gp) expression was examined by Western blot. In vivo, lung solid tumor was formed in mouse LLC cells via intravenous injection. Platycodin D and doxorubicin(alone or in combination) were used to treat tumor-bearing mice for four weeks, and then the tumor size was examined, mouse survival time was recorded, doxorubicin uptake in lung tissues was tested, and lung tissues were stained for observation by HE(hematoxylin-eosin) and immunohistochemistry. The results showed that platycodin D at the experimental concentration had no effect on LLC cell proliferation but decreased LLC cell volume, promoted the cells to uptake doxorubicin and enhanced the inhibitory action of doxorubicin on cell proliferation. Platycodin D could promote GJIC and lysosomal function, increase autophagy and autophagic degradation and suppress P-gp expression. Platycodin D at the experimental dose in this study had no effect on LLC lung solid tumors in mice, increased doxorubicin uptake in lung tissues and enhanced the therapeutic efficacy of doxorubicin on lung solid tumors. Platycodin D could improve the extracellular matrix deposition in lung solid tumors, decreased the lung mucin 5 AC secretion and pulmonary vessel permeability. In summary, platycodin D had the guiding role in treating mouse lung cancer with doxorubicin, and its guiding mechanism may be associated with the promotion of cell communication, lysosomal function, and improvement of extracellular environment.

Bioactive flavonoids from Rubus corchorifolius inhibit α-glucosidase and α-amylase to improve postprandial hyperglycemia.

This research established an optimized method for the extraction and enrichment of flavonoids from R. corchorifolius fruit. Under the optimized extraction conditions, 12 flavonoids (1-12) were isolated, of which six (2-4, 9-10, 12) were obtained from R. corchorifolius for the first time. Compound 4 showed significant α-glucosidase (4.96 µM) and α-amylase (8.04 µM) inhibitory effects. Molecular modeling revealed that compound 4 exhibits strong binding with the active sites of α-glucosidase and α-amylase. Lineweaver-Burk plot analysis and surface plasmon resonance revealed the possible dynamic binding mechanism of the flavonoids with α-glucosidase and α-amylase. The enriched flavonoids and compound 4 showed significant hypoglycemic effects in mice administered a high dose of glucose. In this study, a variety of flavonoids with hypoglycemic activity were found for the first time, revealing the rich chemical composition of R. corchorifolius fruit and highlighting the potential value of R. corchorifolius fruit flavonoids as dietary supplements.

Identification of Cyanidin-3-arabinoside Extracted from Blueberry as a Selective Protein Tyrosine Phosphatase 1B Inhibitor.

Protein tyrosine phosphatase 1B (PTP1B) is an important target for type 2 diabetes. PTP1B inhibitors can reduce blood glucose levels by increasing insulin sensitivity. Anthocyanins often play a hypoglycemic effect, but the research about them have mainly focused on glucosidase. At present, the research about protein tyrosine phosphatase 1B (PTP1B) target is less, and the corresponding molecular mechanism is still unclear. Therefore, in this present study, anthocyanins isolated from blueberry were used to study the inhibitory activity on PTP1B. The isolated cyanidin-3-arabinoside (Cya-3-Ara) exhibited a better inhibitory activity with IC50 = 8.91 ± 0.63 µM, which was higher than the positive control (oleanolic acid, IC50 = 13.9 ± 1.01 µM), and the mechanism of PTP1B inhibition was reversible mixed pattern. The structure-activity relationship (SAR) between anthocyanins and PTP1B inhibition was investigated. The enzyme activity inhibition and molecular docking showed that anthocyanins had high selectivity for PTP1B inhibition. Further study showed that Cya-3-Ara could promote glycogen synthesis through ameliorating PTP1B-involved IRS-1/PI3K/Akt/GSK3ß pathways. Cya-3-Ara could also be regarded as a synergistic inhibitor (CI ≤ 0.54) of oleanolic acid to obtain a better inhibitory effect on PTP1B. Taken together, our study clearly illustrates the SAR between anthocyanins and PTP1B inhibition and the mechanism of Cya-3-Ara in the insulin signaling pathway.

Renoprotective Effect of Yiqi Yangyin Huayu Tongluo Formula against Diabetic Nephropathy in Diabetic Rats.

Diabetic nephropathy is developed in 20-40% of patients with diabetes mellitus, and patients with diabetic nephropathy require dialysis and renal transplantation. Traditional Chinese medicine has been widely used in treating patients with diabetic nephropathy in China. However, the detailed mechanisms of traditional Chinese medicine remain unclear. Yiqi Yangyin Huayu Tongluo formula (ZY formula) is a traditional Chinese medicinal formula. Here, we demonstrated kidney protective effect of ZY formula on the rats with diabetic nephropathy. The therapeutic effect of ZY formula on the diabetic nephropathy was almost the same as that of Irbesartan, which proved to have excellent curative effects on diabetic nephropathy. We also demonstrated the mechanism of ZY formula effect on the diabetic nephropathy. First, we validated that the activation of ROS-JNK signaling pathway in diabetic rats could be reduced by ZY. Furthermore, collagen I expression could be downregulated by ZY formula treatment. Meanwhile, cell apoptosis in the kidney of diabetic rats could be alleviated by ZY formula.

Trait-Based Community Assembly along an Elevational Gradient in Subalpine Forests: Quantifying the Roles of Environmental Factors in Inter- and Intraspecific Variability.

Understanding how communities respond to environmental variation is a central goal in ecology. Plant communities respond to environmental gradients via intraspecific and/or interspecific variation in plant functional traits. However, the relative contribution of these two responses to environmental factors remains poorly tested. We measured six functional traits (height, leaf thickness, specific leaf area (SLA), leaf carbon concentration (LCC), leaf nitrogen concentration (LNC) and leaf phosphorus concentration (LPC)) for 55 tree species occurring at five elevations across a 1200 m elevational gradient of subalpine forests in Yulong Mountain, Southwest China. We examined the relative contribution of interspecific and intraspecific traits variability based on community weighted mean trait values and functional diversity, and tested how different components of trait variation respond to different environmental axes (climate and soil variables). Species turnover explained the largest amount of variation in leaf morphological traits (leaf thickness and SLA) across the elevational gradient. However, intraspecific variability explained a large amount of variation (49.3%-76.3%) in three other traits (height, LNC and LPC) despite high levels of species turnover. The detection of limiting similarity in community assembly was improved when accounting for both intraspecific and interspecific variability. Different components of trait variation respond to different environmental axes, especially soil water content and climatic variables. Our results indicate that intraspecific variation is critical for understanding community assembly and evaluating community response to environmental change.

Esculin improves dyslipidemia, inflammation and renal damage in streptozotocin-induced diabetic rats.

BACKGROUND: Increasing studies have shown that dyslipidemia and inflammatory responses play important roles in the progression of microvascular diabetic complications. Esculin (ES), a coumarin derivative, was extracted from Fraxinus rhynchophylla. The present study was to evaluate the potential effects of ES on lipid metabolism, inflammation responses and renal damage in streptozotocin (STZ)-induced experimental diabetic rats and explore the possible mechanism. METHODS: Diabetic rat model was established by administration high-glucose-fat diet and intraperitoneal injection of STZ 45 mg/kg. ES was administrated to diabetic rats intragastrically at 10, 30 and 90 mg/kg for 10 weeks respectively. The levels of triglycerides (TG), total cholesterol (T-CHO), low density lipoproteins (LDL), and high-density-cholesterol (HDL-C) in serum were measured. IL-1, IL-6, ICAM-1, NO, NAGL, and AGEs level in serum were detected by ELISA assay. The accumulation of AGEs in kidney tissue was examined by immunohistochemistry assay. RESULTS: The results showed that ES could decrease TG, T-CHO, LDL levels in serum of diabetic rats in a dose dependent manner. ES also decreased IL-1, IL-6, ICAM-1, NO and NGAL levels in serum of diabetic rats in a dose dependent manner. Furthermore, ES at 30 and 90 mg/kg significantly decreased AGEs level in serum and alleviated AGEs accumulation in renal in diabetic rats. CONCLUSIONS: Our findings indicate that ES could improve dyslipidemia, inflammation responses, renal damage in STZ-induced diabetic rats and the possible mechanism might be associated with the inhibition of AGEs formation.

Echinacoside Protects against 6-Hydroxydopamine-Induced Mitochondrial Dysfunction and Inflammatory Responses in PC12 Cells via Reducing ROS Production.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DA) neurons at the substantia nigra. Mitochondrial dysfunction and inflammatory responses are involved in the mechanism of cell damage in PD. 6-Hydroxydopamine (6-OHDA), a dopamine analog, specifically damages dopaminergic neurons. Echinacoside (ECH) is a phenylethanoid glycoside isolated from the stems of Cistanche salsa, showing a variety of neuroprotective effects in previous studies. The present study was to investigate its effect against 6-OHDA-induced neurotoxicity and possible mechanisms in PC12 cells. The results showed that 6-OHDA reduced cell viability, decreased oxidation-reduction activity, decreased mitochondrial membrane potential, and induced mitochondria-mediated apoptosis compared with untreated PC12 cells. However, echinacoside treatment significantly attenuated these changes induced by 6-OHDA. In addition, echinacoside also could significantly alleviate the inflammatory responses induced by 6-OHDA. Further research showed that echinacoside could reduce 6-OHDA-induced ROS production in PC12 cells. These results suggest that the underlying mechanism of echinacoside against 6-OHDA-induced neurotoxicity may be involve in attenuating mitochondrial dysfunction and inflammatory responses by reducing ROS production.

Aggressive interventions in terminally ill patients with solid tumors in China: a retrospective single center analysis.

PURPOSE: Overtreatment in terminally ill cancer patients is very common worldwide, but whether patients will benefit from aggressive care remains obscure. This study aimed to explore the value of aggressive interventions in the end of life in adult patients with advanced solid tumors. METHODS: All adult patients who died from advanced solid tumors between 2011 and 2012 in Xiangyang Central Hospital were included. Detailed data concerning cancer types, therapy approach and outcome in the last three months of life were collected and assessed. RESULTS: 263 patients with median age 63 years died of cancer between 2011 and 2012. In the last 3 months of life, 82.5% of the patients received aggressive care, especially chemotherapy and radiotherapy. Traditional Chinese medicine was widely used. Median survival from diagnosis of metastasis to death was 6.9 months for patients treated with aggressive care and 6.2 months for the others, respectively (p>0.05). CONCLUSION: Despite their wide use, aggressive interventions in the last 3 months of life might have no benefit on survival. Radiotherapy provided significant symptom palliation of bone or brain metastases, but the short-course radiotherapy schedule was rarely used. Frequent reassessment of patients and making decision together with the patients is helpful to overcome the aggressive care. Appropriate tools to predict survival are needed to help design proper strategies for terminally ill cancer patients.

Two xanthones from Swertia punicea with hepatoprotective activities in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice. MATERIALS AND METHODS: The active hepatoprotective constituents of Swertia punicea were purified using various column chromatography techniques. The structures of two isolated compounds were determined on the basis of spectroscopic data interpretation such as NMR analysis. The hepatoprotective activities of isolated compounds were evaluated by using hepatotoxicity in vitro and dimethylnitrosamine-induced rat hepatic fibrosis in vivo, respectively. RESULTS: Two xanthones, 1, 7-dihydroxy-3, 4, 8-trimethoxyxanthone (1) and bellidifolin (2) were isolated from the stems of Swertia punicea. The compounds 1 and 2 exhibited notable hepatoprotective activities against carbon tetrachloride (CCl4) -induced HepG2 cell damage, and effectively alleviated the levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malonic dialdehyde (MDA) induced by CCl4 in a concentration-dependent manner. Co-treatment with compound 2 significantly increased the cell viability compared with N-acetyl-p-aminophenol (APAP) treatment. Compound 2 also alleviated APAP-induced hepatotoxicity by increasing glutathione (GSH) content and decreasing hydroxyl free radical (·OH) levels and reactive oxygen specises (ROS) production. In addition, the protective effect of compound 1 significantly alleviated DMN-induced liver inflammation and fibrosis. Oral administration of compound 1 recovered the reduction of albumin (ALB) and reversed the elevation of serum alanine transaminase (ALT), AST and total bilirubin (TBIL) in dimethylnitrosamine (DMN)-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by a 1.5-fold elevation in MDA and a fall in the SOD activity, and treatment with compound 1 protected against these adverse effects. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by compound 1 is also confirmed by H&E and Masson stained histopathological evaluation of liver tissue. CONCLUSION: Two xanthones from Swertia punicea exhibited hepatoprotective activities in vitro (compounds 1 and 2) and in vivo (compound 1), respectively.

[Isolation and diversity analyses of endophytic fungi from Paris polyphylla var. yunnanensis].

The paper is aimed at studying the diversity of endophytic fungi community from Paris polyphylla var. yunnanensis, and to provide a scientific basis for the utilization value of the endophytic fungi as bioactive material resources. In the present study, endophytic fungi were isolated from roots, rhizomes and leaves of wild P. polyphylla var. yunnanensis collected from Baoshan, Heqing county and Songming city of Yunnan province, and identified and classified by morphological methods together with its ITS sequence analysis. Seven and forty-nine strains of endophytic fungi were isolated from P. polyphylla var. yunnanensis. They were identified belonging to 41 genus. In these 41 genus, 3 genus exist in root only, 12 genus only exist in rhizome and 8 genus only exist in leaf. There was difference in endophytic fungi isolated from different sample sites. Endophytic fungi diversity from rhizomes of Heqing site was the highest. Endophytic fungi similarity coefficient was low among different sites and tissues. Based on these results, it is reasonable to propose that endophytic fungi of P. polyphylla var. yannanensis from different tissue and different sample sites has a certain difference which is possibly relate to their different habitats, different structure and composition of each tissue.

[Efficacy observation of treating early and midterm chronic renal failure patients by qi supplementing, collateral dredging, detoxifying, and turbidity descending recipe combined with basic methods of Western medicine].

OBJECTIVE: To observe therapeutic efficacy of treating early and midterm chronic renal failure (CRF) patients by qi supplementing, collateral dredging, detoxifying, and turbidity descending recipe (QSCDDTDR) combined with basic methods of Western medicine (WM). METHODS: Totally 160 early and midterm CRF patients were recruited from Hebei Hospital of Traditional Chinese Medicine, Hebei Medical University from January 2007 to December 2011. They were randomly assigned to the treatment group and the control group, 80 in each group. On the basis of basic treatment of WM, QSCDDTDR was given to patients in the treatment group, while niaoduqing granule (NDQG) was given to those in the control group. After 12 months of treatment, the therapeutic efficacy, Chinese medicine (CM) symptom scores, serum creatinine (SCr), blood urine nitrogen (BUN), 24 h urine protein quantitation, hemoglobin (Hb), and the occurrence of end-point events were observed. RESULTS: The total effective rate in the treatment group was 77.6% (28/76), obviously higher than that in the control group [(58.1%, 43/74), P < 0.05]. After treatment the CM syndrome scores obviously decreased in the treatment group (18.3 +/- 5.3), obviously lower than before treatment (26.0 +/- 4.4) and the control group (22.4 +/- 4.9) (P < 0.05, P < 0.01). The levels of SCr, BUN, and 24 h urine protein quantitation were (169.1 +/- 22.6) micromol/L, (10.4 +/- 2.0) mmol/L, (861.4 +/- 232.7) mg/24 h, respectively, in the treatment group after treatment, which were lower than before treatment [(204.1 +/- 27.7) micromol/L, (13.2 +/- 3.2) mmol/L, (1 287.5 +/- 442.3) mg/24 h, P < 0.01). The aforesaid indices were also improved in the control group after treatment (P < 0.05, P < 0.01). The decrease in SCr, BUN, and 24 h urine protein quantitation after treatment was more obviously in the treatment group than in the control group [(185.8 +/- 23.9) micromol/L, (11.2 +/- 2.5) mmol/L, (1014.5 +/- 301.7) mg/24 h; P < 0.05, P < 0.01). The incidence rate of the end-point events was 10.53% (8/76) in the treatment group and 13.51% (10/74) in the control group, but with no statistical difference. CONCLUSION: QSCDDTDR combined with basic methods of WM showed better therapeutic efficacy in improving the renal function and reducing the level of urinary protein of the early and midterm CRF patients.

[Effects of Chinese materia medica of qi benefiting, yin nourishing, stasis removing, and collaterals dredging and their dissembled recipes on nephrin of diabetes mellitus model rats].

OBJECTIVE: To observe the effects of Chinese materia medica (CMM) of qi benefiting, yin nourishing, stasis removing, and collaterals dredging (QBYNSRCD) and their dissembled recipes on nephrin of diabetes mellitus (DM) model rats. METHODS: The DM model was induced by high fat diet combined with low dose STZ. Rats in the normal control group (abbreviated as Group N) and the model group (abbreviated as Group M) were administered with ultrapure water at corresponding volume by gastrogavage. Rats in the CMM of QBYNSRCD treatment group (abbreviated as Group YHT) were administered with CMM of QBYNSRCD, composed of milkvetch root, rehmannia root, danshen root, chuanxiong (2 packages each), solomonseal, earth worm, leech, and scorpion (1 package each), which was administered at 1.0 g/kg. Rats in the CMM of qi benefiting, yin nourishing, and stasis removing (QBYNSR) treatment group (abbreviated as Group YT) were administered with CMM of QBYNSR, composed of milkvetch root, rehmannia root, danshen root, chuanxiong (2 packages each), and solomonseal (1 package each), which was administered at 0. 92 g/kg. Rats in the CMM of qi benefiting, yin nourishing, and collaterals dredging (QBYNCD) treatment group (abbreviated as Group YT) were administered with CMM of QBYNCD, composed of milkvetch root, rehmannia root (2 packages each), solomonseal, earth worm, leech, and scorpion (1 package each), which was administered at 0.79 g/kg. The volume was set to 1 mL/100 g, once daily by gastrogavage, for total 32 weeks. Rats' body weight was measured. By the end of medication, urinary creatinine (UCr), 24-h urinary albumin (U-alb), and urinary nephrin (U-nephrin), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), serum creatinine (SCr), and nephrin of kidney tissues homogenate (K-nephrin) were detected. The renal tissue sections were stained with Masson. The pathomorphological changes were observed. RESULTS: The body weight of rats in Group N increased gradually. After modeling, the body weight of rats in Group M and all medicated groups obviously decreased. Compared with Group M, the decreased body weight was not obvious in all medicated groups, still showing statistical difference (P < 0.01). Compared with Group N, U-alb and U-nephrin in Group M significantly increased (P < 0.01) in a positive linear correlation (r = 0.941, P = 0.017). K-nephrin significantly decreased, and K-nephrin had a negative linear correlation with U-alb (r = -0. 987, P = 0.002). FBG, CCr, and HbA1c significantly increased (P < 0.01). Glomeruli were obviously enlarged under light microscope, with obviously increased extracellular matrix accumulation. Compared with Group M, corresponding indices were obviously improved ( P < 0.01) except FBG and HbA1c in Group YT. As for inter-group comparison among all medicated groups, the improvement of CCr was the best in Group YHT with statistical difference shown (P < 0.01). There was no statistical difference for the rest indices (P > 0.05). When compared with Group M, the hypertrophy of glomerulus was not so obvious in all medicated groups. Neither was extracellular matrix accumulation. CONCLUSIONS: CMM of QBYNSRCD and dissembled recipes showed renal protection on DM model rats. One of its action pathways might be reducing the loss of nephrin, thus reducing U-alb.

Relationship between urinary nephrin and urinary albumin changes in diabetic rats and effects of yiqiyangyinhuayutongluo recipe.

OBJECTIVE: To investigate the dynamic changes of urinary nephrin, and the relationship between it and urinary albumin excretion rate (UAER) in a diabetic rat model, as well the effects of yiqiyangyinhuayutongluo recipe. METHODS: Diabetic model was induced by high fat diet combined with low-dose Streptozotocin (STZ) in rats. Normal group (NG), model group (MG), and yiqiyangyinhuayutongluo recipe treated group (YHTG) were set. Gastrointestinal Yiqiyangyi-nhuayutongluo recipe was administered once daily for 32 w. At the end of the 2nd w (2 w), 8 w, 16 w, and 32 w, fasting blood glucose (FBG), UAER and 24h urinary nephrin (U-nephrin) were detected. RESULTS: Compared with NG, FBG in MG increased notably (P < 0.05). Compared with MG, FBG of YHTG (P < 0.05) since 16 w. U-nephrin and UAER in MG increased significantly from 2 w, peaked at 16 w, lessened in different degree at 32 w, but were still higher than NG. The correlation analysis showed that there was a significant positive correlation between U-nephrin and UAER at different time, the correlation coefficient as r > 0.9, and P < 0.05. Compared with MG, U-nephrin and UAER in YHTG decreased markedly (P < 0.05) except for U-nephrin at 8 w. CONCLUSIONS: U-nephrin and UAER in diabetic rat model have a positive linear correlation. Yiqiyangyinhuayutongluo recipe can reduce UAER markedly, and preventing the lose of nephrin in urine maybe one of the mechanisms.

[Effects of the effective component group of Chinese herbal medicine Xiaoxuming Decoction on brain mitochondria in rats with chronic cerebral ischemia].

OBJECTIVE: To investigate the effects of the effective component group of Xiaoxuming Decoction (XXM), a compound traditional Chinese herbal medicine, on cerebral mitochondria in rats with chronic cerebral ischemia. METHODS: Rats were subjected to permanent bilateral common carotid artery occlusion to induce chronic cerebral ischemia. Then, the rats with chronic cerebral ischemia were randomly divided into five groups: model group, extract of Ginkgo biloba group and low-, medium- and high-dose effective component group of XXM groups. Another 11 rats without common carotid artery occlusion were used as a sham control. Gradient centrifugation was used to obtain the mitochondria from the rat brain. Clark oxygen electrode method was used to determine mitochondrial respiratory function. Photometric determination was used to measure mitochondrial swelling. Rodamine 123 was used to measure mitochondrial membrane potential. Western blotting was used to detect mitochondrial apoptosis. RESULTS: Compared with the sham group, the mitochondria dysfunction was caused by chronic cerebral ischemia associated with the decrease of oxidative phosphorylation parameters and the mitochondrial membrane potential, the increase of the mitochondrial degree, the elevation of reactive oxygen species level, the decrease in Bcl-2/Bax ratio, and the release of cytochrome c. The effective component group of XXM could reduce mitochondrial damage induced by chronic cerebral ischemia by improving the indexes mentioned above. CONCLUSION: The effective component group of Xiaoxuming Decoction can protect brain mitochondrial homeostasis and improve the function of mitochondria in rats with chronic cerebral ischemia, which may be the mechanism of its protection against chronic cerebral ischemia.

[Clinical observation of treating early diabetic nephropathy by qi supplementing, yin nourishing, blood stasis dispersing, collateral dredging recipe].

OBJECTIVE: To observe therapeutic effects of qi supplementing, yin nourishing, blood stasis dispersing, collateral dredging recipe (QYBCR) on early diabetic nephropathy (DN). METHODS: Seventy-eight early DN patients were randomly assigned to the treatment group (39 cases, treated by QYBCR) and the control group (39 cases, treated by irbesartan). The changes of the therapeutic efficacy, Chinese medicine syndrome scores, urine albumin excretion rate (UAER), serum creatinine (SCr), blood urine nitrogen (BUN), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and the occurrence of end-point events were observed after one-year treatment. RESULTS: The total effective rate in treatment group was 83.8% (31/37 cases), which was obviously higher than that in control group (60.5%, 23/38 cases) (P < 0.05). After treatment the Chinese medicine syndrome scores were reduced significantly in the treatment group (P < 0.05, P < 0.01), and showed significant difference when compared with those in the control group (P < 0.05, P < 0.01). Levels of UAER, SCr, BUN, FBG, TC, and TG were (65. 78 +/- 9.67) microg/min, (93.20 +/- 12.99) micromol/L, (5.69 +/- 1.21) mmol/L, (6.14 +/- 1.47) mmol/L, (4. 85 +/- 0. 83) mmol/L, (1.46 +/- 0.81) mmol/L after treatment in treatment group. All of them decreased more significantly than before treatment [(161.03 +/- 20.01) microg/min, (101.11 +/- 14.33) micromol/L, (6.54 +/- 1.12) mmol/L, (9.27 +/- 2.32) mmol/L, (6. 19 +/- 2.13) mmol/L, (2. 70 +/- 1.86) mmol/L] (P < 0.05, P < 0.01). The aforesaid indices were also improved in the control group after treatment (P < 0.05, P < 0.01). The reduction of TC and TG after treatment in the treatment group was more significant [(5.58 +/- 1.57) mmol/L, (1.99 +/- 1.22) mmol/L] (P < 0.05). Besides, the incidence rate of end-point events (5.4%, 2/37) (1 year after the development of clinical DN) of the treatment group was slightly lower than that of the control group (10.5%, 4/38), but with no statistical difference. CONCLUSION: QYBCR combined with Western medicine-based treatment showed better therapeutic efficacy on early DN.

[Effects of the active components of Chinese herbal medicine Xiaoxuming Decoction on memory behavior and brain injury in rats with chronic cerebral ischemia].

OBJECTIVE: To study the effects of the active components of Xiaoxuming Decoction (XXM), a compound traditional Chinese herbal medicine, on chronic cerebral ischemia in rats. METHODS: Chronic cerebral ischemia was induced in rats by occlusion of bilateral common carotid arteries. Then, the rats with chronic cerebral ischemia were randomly divided into five groups: model group, extract of Ginkgo biloba group and low-, medium- and high-dose active components of XXM groups. Another 11 rats without occlusion of common carotid arteries were used as the sham-operation group. Memory behavior was investigated by Morris water maze test. The structure of hippocampus and cortex neurons was observed with Nissel staining. The white matter lesion was stained with Klüver-Barrera stain method to observe the pathological changes. The astrocyte activation was observed using immunohistochemical method with glial fibrillary acidic protein (GFAP) antibody. RESULTS: The active components of XXM could significantly improve the impairment of learning and memory induced by chronic cerebral ischemia in rats. Compared with the model group, the time to reach the platform for rats was shortened by treating with the active components of XXM in Morris water maze test, particularly in the medium-dose group (P<0.05). In addition, the low- and medium-dose active components of XXM improved the decrease of cerebrovascular reactivity induced by chronic cerebral ischemia. The results of the pathological analysis also suggested that the active components of XXM could ameliorate the pathological damage induced by chronic cerebral ischemia in rats with the number of neurons increased, and the morphology and distribution of neurons recovered to normal levels. The low-dose active components of XXM significantly reduced the white matter lesions (P<0.05, P<0.01). Active components of XXM treatment could also reduce the activation of astrocytes. CONCLUSION: The active components of XXM may attenuate the chronic cerebral ischemic injury in rats.

[Establish efficiently transformation system of the Isatis indigotica].

OBJECTIVE: To build up a method of efficiently transforming Isatis indigotica with the Agrobacterium. METHODS: Two kinds of Agrobocterium: ATCC 15834 and RI1601 were used to treat different fraction of Isatis indigotica. Explored the effect of cocultured, different antibiotic concentration and the media on multiply the hairy roots. RESULTS: The explants with out coculture had had higher survival rate rooting rate and earlier sprout time. After ultrasonic treatment of plant, the indacement rate was two times than that of untreated one; The best antibiotic concentration was 400 mg/L; The proportion of the grow speed of the hairy root in the liquid culture media was 2 - 3 times than that of solid culture media, and 37 times of common roots. CONCLUSION: The method is useful for establishing an efficiently transformatiem system of Isatis indigotica by Agrobacterium.

[Effect of treatment of non-nephrotic syndrome IgA nephropathy with Shenyanning].

OBJECTIVE: To observe the curative effect of Shenyanning (SYN) on non-nephrotic syndrome IgA nephropathy (IgAN). METHODS: Seventy primary IgAN patients were equally randomized into two groups, the treatment group and the control group, they were orally treated with SYN Decoction (one dose per day) and Losartan (50 mg per day) respectively for 1 year. Efficacy of treatment, Chinese medicine syndrome scores, end-point events occurrence as well as changes of related laboratory indices were observed. RESULTS: The total effective rate in the treatment group was obviously higher than that in the control group (77.1% vs. 54.3%, P < 0.05). After treatment, the Chinese medicine syndrome scores, urinary protein and urinary red-cell count reduced significantly in the treatment group (P < 0.05 or P < 0.01) and showed significant difference as compared with those in the control group (P < 0.05 or P < 0.01); while the endogenous creatinine clearance was changed insignificantly in both groups. Beside, the occurrence of end-point events in the treatment group was slightly lower than that in the control group, though showed no statistical difference between them. CONCLUSION: The curative effect of SYN in treating IgAN was obviously better than that of simple Western medicine.