Deciphering the pharmacological mechanisms of Scutellaria baicalensis Georgi on oral leukoplakia by combining network pharmacology, molecular docking and experimental evaluations.

BACKGROUND: Oral leukoplakia (OLK), an uncharacterized pathological condition that occurs as a white patch in the oral mucosa, is the most common precancerous condition. Scutellaria baicalensis Georgi (SBG) is a medicinal plant with a wide range of pharmacological effects. Increased evidence shows that SBG has potential therapeutic effects on OLK. However, the therapeutic mechanisms of SBG against OLK have not yet been completely elucidated. PURPOSE: This study aimed to clarify the active components and multi-target mechanisms of SBG against OLK via network pharmacology, molecular docking and experimental evaluations. STUDY DESIGN AND METHODS: The active components and related targets of SBG were screened by the TCMSP database and Swiss Target Prediction database. Potential therapeutic targets of OLK were collected using the GeneCards and OMIM databases. Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OLK via applying data mining techniques and topological parameters. Metascape database was utilized for GO and KEGG pathway analysis. Molecular docking techniques were used to estimate the binding force between the components and the hub genes. Subsequently, a series of in vitro experiments, specifically CCK-8 assay, clone formation assay, wound healing assay, flow cytometry, RT-qPCR and western blotting were conducted for further verification. RESULTS: There were 25 active components and 31 related target genes in SBG against OLK. PPI analysis showed that Akt1, VEGFA, EGFR, HIF1A and PTGS2 shared the highest centrality among all target genes. KEGG pathway analysis found that PI3K-Akt signaling pathway may occupy core status in the anti-OLK system. Molecular docking results showed that the main active components of SBG had a strong binding affinity to the hub genes. In vitro experiments showed that the leading component baicalein may inhibit proliferation, block cells in the S phase, induce DOK cell apoptosis, and downregulate the mRNA expression of 5 hub genes by inhibiting PI3K/Akt signaling pathway activation. CONCLUSION: The most predominant component of SBG against OLK was baicalein and the key pathway was PI3K/Akt. The main components and hub genes had robust binding abilities. In vitro experiments showed that baicalein could inhibit the proliferation of DOK cells, induce apoptosis, block the cell cycle, and inhibit the mRNA expression level of the hub genes by inhibiting the PI3K/Akt pathway.

Habitual Fish Oil Supplementation and Incident Chronic Kidney Disease in the UK Biobank.

BACKGROUND: To explore the relation of habitual fish oil use with the risk of chronic kidney diseases (CKD). METHODS: 408,023 participants (54.2% female) without prior CKD and with completed information regarding their consumption of major food groups and fish oil in the UK Biobank were enrolled. Fish oil use and dietary intakes were assessed by touch screen questionnaire and food frequency questionnaire, respectively. Incident CKD was recorded from hospital inpatient records. RESULTS: At baseline, 128,843 (31.6%) participants reported taking fish oil supplements. During a median follow-up period of 12.0 years, a total of 10,782 (2.6%) participants developed CKD. With adjustments for important confounders, habitual fish oil use was associated with a significantly lower hazard of incident CKD (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.87-0.95), compared with non-use. Consistently, participants reporting ≥2 servings/week of oily fish (HR, 0.86; 95% CI, 0.79-0.94) and nonoily fish (HR, 0.86; 95% CI, 0.77-0.97) consumption had a lower hazard of incident CKD compared to those reporting no consumption ever. Additionally, among the 97,914 participants with data on plasma fatty acid, there were significant inverse relationships of plasma omega-3 polyunsaturated fatty acid (PUFA) (per SD increment, HR, 0.89, 95% CI, 0.84-0.94) and eicosatetraenoic acid (per SD increment, HR, 0.91, 95% CI, 0.87-0.96) with incident CKD. CONCLUSIONS: Habitual fish oil use was associated with a lower hazard of CKD, which was further confirmed by the consistent inverse relations between fish consumption and circulating omega-3 PUFA concentration with incident CKD.

Exploring the Mechanism of Scutellaria baicalensis Georgi Efficacy against Oral Squamous Cell Carcinoma Based on Network Pharmacology and Molecular Docking Analysis.

BACKGROUND: Scutellaria baicalensis Georgi (SBG) has been widely shown to induce apoptosis and inhibit invasion and migration of various cancer cells. Increased evidence shows that SBG may be useful to treat oral squamous cell carcinoma (OSCC). However, the biological activity and possible mechanisms of SBG in the treatment of OSCC have not been fully elucidated. This study aimed to clarify the bioactive component and multitarget mechanisms of SBG against OSCC using network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to predict the active components in SBG, and putative molecular targets of SBG were identified using the Swiss Target Prediction database. OSCC-related targets were screened by GeneCards, Online Mendelian Inheritance in Man (OMIM), and Therapeutic Target Database (TTD). Then, we established protein-protein interaction (PPI), compound-target-disease (C-T-D), and compound-target-pathway (C-T-P) networks by Cytoscape to identify the main components, core targets, and pharmacological pathways of SBG against OSCC via applying data mining techniques and topological parameters. Metascape database was utilized for Gene Ontology (GO) and pathway enrichment analysis. The potential interaction of the main components with core targets was revealed by molecular docking simulation, and for the correlation between core targets and OSCC prognosis analysis, the Kaplan-Meier Plotter online database was used. RESULTS: There were 25 active compounds in SBG and 86 genes targeted by OSCC. A total of 141 signaling pathways were identified, and it was found that the PI3K-Akt signaling pathway may occupy core status in the anti-OSCC system. GO analysis revealed that the primary biological processes were related to apoptosis, proliferation, and migration. Molecular docking results confirmed that core targets of OSCC had a high affinity with the main compounds of SBG. CONCLUSION: Our study demonstrated multicomponent, multitarget, and multipathway characteristics of SBG in the treatment of OSCC and provided a foundation for further drug development research.

Quantitative reduction in short-chain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease.

Chronic kidney disease (CKD) affects 10-15% of the population worldwide, results in high morbidity and mortality, and requires costly treatment and renal replacement therapy. Glomerulosclerosis, tubulointerstitial fibrosis, and persistent intestinal flora disturbance are common in CKD. Short-chain fatty acids (SCFAs), produced by the intestinal microbiota, have been previously reported to ameliorate kidney injury; however, the specific concentrations and types that are required to improve renal function remain unknown. The present study aims to evaluate the levels of SCFAs in healthy and CKD patients, and to test the hypothesis that SCFAs play a critical role in delaying CKD progression. One hundred and twenty-seven patients with CKD and 63 healthy controls from China were enrolled in the present study. Butyrate, which is considered beneficial to humans, was almost three-times higher in healthy volunteers than that in CKD5 subjects (P=0.001). Moreover, the serum SCFA levels in controls were significantly higher than that in CKD patients (P<0.05), and the butyrate level among CKD5 patients (1.48 ± 0.60 µmol/l) was less than half of that in controls (3.44 ± 2.12 µmol/l, P<0.001). In addition, we observed an inverse correlation between butyrate level and renal function (P<0.05). A CKD rat model transplanted with microbiota obtained from CKD patients exhibited accelerated CKD progression via increased production of trimethylamine N-oxide (TMAO), which was reversed by supplementation with extra butyrate. Our results showed that SCFA levels were reduced in CKD patients and that butyrate supplementation might delay CKD progression.

Association Between Folic Acid Supplementation and Retinal Atherosclerosis in Chinese Adults With Hypertension Complicated by Diabetes Mellitus.

Background: This cross-section investigation included 2,199 participants with hypertension complicated by diabetes mellitus, a cohort of the China Stroke Primary Prevention Trial in which 20,702 patients with essential hypertension were given enalapril with folic acid or enalapril-only double-blind treatment for 5 years. This study aimed to explore the correlation between folic acid supplementation and retinal atherosclerosis (RA) in adults with hypertension complicated by diabetes mellitus. Methods: The diagnosis of RA was determined by non-mydriatic fundus photography and classified by the Keith-Wagener-Barker system. The statistical correlation of folic acid supplementation with RA prevalence and severity was assessed. Results: Of our cohort, 1,698 (77.6%) participants were diagnosed with RA, and the prevalence in males and females was 78.0 and 75.6%, respectively. Participants in the enalapril group had higher total homocysteine (tHcy) levels than those in enalapril-folic acid group. Compared with the enalapril group in the tHcy > 15 µmol/L group of females, the odds ratio for the enalapril-folic acid group was 0.28 (95% confidence interval, 0.11-0.67, P = 0.0061). Conclusions: The prevalence of RA was high (77.6%) in our cohort of adults with hypertension complicated by diabetes mellitus. Folic acid supplementation was significantly associated with reduced risk of RA in females with hyperhomocysteinemia. No significant association were seen in males.

Lingzhilactones from Ganoderma lingzhi ameliorate adriamycin-induced nephropathy in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Several Ganoderma fungi are well-known for their medical uses to treat cancer, insomnia and kidney disease in East Asia. Triperpenoids and polysaccharides have been considered for a long time to be the major active components of the genus Ganoderma. The present study is to examine the effects of lingzhilactones from G. lingzhi on adriamycin-induced nephropathy in mice. MATERIALS AND METHODS: A combination of various chromatography led to the isolation of lingzhilactones A-C, their structures were identified by spectroscopic and computational methods. The intracellular reactive oxygen species (ROS) was detected with the carboxymethyl-H2-dichlorofluorescein diacetate fluoroprobe. The fibrotic markers were analyzed by real-time RT-PCR and Western blot analyses. Detection of SEAP was conducted with the chemiluminescent. Urine albumin was measured using an ELISA assay. Histology and immunohistochemical staining was used to assess fibrotic lesions in mice. RESULTS: Three new lingzhilactones A-C (1-3) containing a fused lactone moiety were isolated from G. lingzhi. We found that 2 could inhibit ROS generation in a dose-dependent manner, inhibit mRNA expression of collagen IV, fibronectin, IL-6 and increase expression of Nrf2 in rat tubular epithelial cells. Furthermore, we found that 2 could reduce urinary albumin levels, abrogate myofibroblastic activation and inhibit the phosphorylation of Smad3 in adriamycin-induced mice. CONCLUSIONS: The in vitro and in vivo results suggested that lingzhilactone B could protect against renal injuries by increasing the activities of antioxidants and inhibiting inflammation. The inhibition of Smad3 phosphorylation suggested that this substance displays in vivo antifibrotic activity by a mechanism that is dependent on disruption of Smad3. These results promote understanding of the traditional usage of G. lingzhi and provide promising findings which may be beneficial for anti-kidney disease drug design.

Sevelamer carbonate lowers serum phosphorus effectively in haemodialysis patients: a randomized, double-blind, placebo-controlled, dose-titration study.

BACKGROUND: Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder. METHODS: This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start. RESULTS: In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease. CONCLUSIONS: This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.

Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The efficacy of homocysteine-lowering therapy with folic acid to lower homocysteine levels in an effort to reduce cardiovascular disease (CVD) risk in patients with kidney disease remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. METHODS: This meta-analysis included 8234 patients with kidney disease from nine qualified randomized trials using folic acid therapy, and with CVD reported as one of the endpoints. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of CVD using a random effects model. RESULTS: When pooling the nine randomized trials, folic acid therapy reduced the risk of CVD by 10%（RR = 0.90; 95% CI:0.81-1.00, P = 0.046). A greater beneficial effect was observed among those trials without a history of grain fortification with folic acid (0.82; 0.70-0.96, P = 0.01), with lower percent baseline diabetes (<30% (median), 0.80; 0.65-0.99, P = 0.04), and in patients with end-stage renal disease (ESRD) or advanced chronic kidney disease (ACKD) (0.85; 0.77-0.94, P = 0.002). Furthermore, a meta-regression analysis suggested a positive dose-response relationship between percent baseline diabetes and log-RR for CVD risk associated with folic acid supplementation (P = 0.007). Most importantly, even the inclusion of three subgroup results did not substantially affect the results (n = 11032, RR: 0.93; 95% CI:0.87-0.99, P = 0.03). CONCLUSIONS: Our meta-analysis indicates that folic acid supplementation may be effective for CVD prevention in patients with kidney disease, particularly in trials among patients without a history of grain fortification with folic acid, with lower percent baseline diabetes, and in patients with ESRD or ACKD.

Mineral and bone disorder in Chinese dialysis patients: a multicenter study.

BACKGROUND: Mineral and bone disorder (MBD) in patients with chronic kidney disease is associated with increased morbidity and mortality. Studies regarding the status of MBD treatment in developing countries, especially in Chinese dialysis patients are extremely limited. METHODS: A cross-sectional study of 1711 haemodialysis (HD) patients and 363 peritoneal dialysis (PD) patients were enrolled. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) were analyzed. The achievement of MBD targets was compared with the results from the Dialysis Outcomes and Practice Study (DOPPS) 3 and DOPPS 4. Factors associated with hyperphosphatemia were examined. RESULTS: Total 2074 dialysis patients from 28 hospitals were involved in this study. Only 38.5%, 39.6% and 26.6% of them met the Kidney Disease Outcomes Quality Initiative (K/DOQI) defined targets for serum P, Ca and iPTH levels. Serum P and Ca levels were statistically higher (P < 0.05) in the HD patients compared with those of PD patients, which was (6.3 ± 2.1) mg/dL vs (5.7 ± 2.0) mg/dL and (9.3 ± 1.1) mg/dL vs (9.2 ± 1.1) mg/dL, respectively. Serum iPTH level were statistically higher in the PD patients compared with those of HD patients (P = 0.03). The percentage of patients reached the K/DOQI targets for P (37.6% vs 49.8% vs 54.5%, P < 0.01), Ca (38.6% vs 50.4% vs 56.0%, P < 0.01) and iPTH (26.5% vs 31.4% vs 32.1%, P < 0.01) were lower among HD patients, compared with the data from DOPPS 3 and DOPPS 4. The percentage of patients with serum phosphorus level above 5.5 mg/dL was 57.4% in HD patients and 47.4% in PD patients. Age, dialysis patterns and region of residency were independently associated with hyperphosphatemia. CONCLUSIONS: Status of MBD is sub-optimal among Chinese patients receiving dialysis. The issue of hyperphosphatemia is prominent and needs further attention.

Diabetic nephropathy-related active cyclic peptides from the roots of Brachystemma calycinum.

Three new cyclic peptides, namely duanbanhuains A-C (1-3), were isolated from the roots of Brachystemma calycinum which is a traditional medicine used to treat rheumatic diseases. Their structures were identified by means of a suite of MS and NMR experiments. These compounds were purposely evaluated for their inhibitory effects on the release of MCP-1, IL-6, collagen IV and reactive oxygen species (ROS) against high-glucose-stimulated mesangial cells. The results showed that compounds 1 and 2 exhibited potent inhibition on the production of IL-6, collagen IV and ROS at the concentration of 10 µM.

Bioactive compounds from the aerial parts of Brachystemma calycinum and structural revision of an octacyclopeptide.

Four new cyclic peptides, brachystemins F-I (1-4), and 11 known compounds were isolated from the aerial parts of Brachystemma calycinum. The absolute configurations of compounds 1-4 were assigned using Marfey's method. The structure of compound 5 was revised from cyclo(Pro¹-Phe²-Leu³-Ala4-Thr5-Pro6-Ala7-Gly8) to cyclo(Pro¹-Pro²-Ala³-Gly4-Leu5-Ala6-Thr7-Phe8) with QTOF/MS and X-ray diffraction analysis. The N-containing compounds were assessed for their inhibitory effects on the secretion of monocyte chemokine ligand 2 (CCL-2), interleukin 6 (IL-6), and collagen IV against high-glucose-stimulated mesangial cells. Compound 5 was evaluated for its effects on collagen I, reactive oxygen species (ROS), superoxide anion (O2(•⁻)) production, and cell viability in mesangial cells, and on nitric oxide (NO) production in macrophage cells.

Isolation and identification of compounds responsible for antioxidant capacity of Euryale ferox seeds.

Euryale ferox seed is consumed medicinally or for food in China. The present study revealed it to contain significant antioxidant activity, which may be associated with its medical applications as a proteinuria inhibitor of diabetic nephropathy. This study resulted in the identification of 3 new sesquineolignans, named euryalins A-C (1-3), and 16 known compounds, which were all first isolated from this plant apart from 5,7,4-trihydroxy-flavanone. The antioxidant potential of the partial isolates was evaluated using the DPPH radical scavenging assay and mesangial cellular assay. Compounds 2, rel-(2α,3ß)-7-O-methylcedrusin (4), syringylglycerol-8-O-4-(sinapyl alcohol) ether (5), and (+)-syringaresinol (7) were found to be most active on DPPH assay, whereas compounds 2, 4, 7, (1R,2R,5R,6S)-2-(3,4-dimethoxyphenyl)-6-(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3.3.0]octane, and buddlenol E could significantly inhibit high glucose-stimulated reactive oxygen species production in mesangial cells. The results suggested that E. ferox seed could be considered as an excellent source of natural antioxidants and is useful in the prevention of diabetic nephropathy.

Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney disease: a meta-analysis.

BACKGROUND AND OBJECTIVES: The efficacy of folic acid therapy to lower homocysteine (Hcy) levels in an effort to reduce cardiovascular disease (CVD) risk in patients with ESRD or advanced chronic kidney disease (ACKD; creatinine clearance, <30 ml/min) remains inconclusive. We conducted a meta-analysis of relevant randomized trials to further examine this issue. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This meta-analysis included 3886 patients with ESRD/ACKD from seven qualified randomized trials using folic acid therapy and with CVD reported as one of the end points. RESULTS: When pooling the seven trials, folic acid therapy reduced the risk of CVD by 15% (RR, 0.85; 95% CI, 0.76 to 0.96; P = 0.009). A greater beneficial effect was observed among those trials with a treatment duration >24 months (RR, 0.84; 95% CI, 0.72 to 0.98; P = 0.02), a decrease in Hcy level >20% (RR, 0.83; 95% CI, 0.73 to 0.95; P = 0.007), and no or partial folic acid fortification (RR, 0.80; 95% CI, 0.65 to 0.99; P = 0.04). The beneficial effect also was seen when Hcy levels decreased >20%, even in the presence of folic acid fortification (RR, 0.85; 95% CI, 0.73 to 0.99; P = 0.04). In the corresponding comparison groups, the estimated RRs were attenuated and insignificant. CONCLUSIONS: Folic acid therapy can reduce CVD risk in patients with ESRD/ACKD by 15%. A greater beneficial effect was observed among those trials with no or partial folic acid fortification or a decrease in Hcy level >20% regardless of folic acid fortification.

Comparisons between oral pulse alfacalcidol therapy and daily therapy in maintenance hemodialysis patients with secondary hyperparathyroidism: a randomized, controlled, and multicenter study.

OBJECTIVE: To investigate the efficacy and safety of 1alpha-(OH)-D3 high-dose pulse therapy or daily low-dose therapy in secondary hyperthyroidism in maintenance hemodialysis patients in China. METHODS: Maintenance hemodialysis patients of both gender with intact parathyroid hormone (iPTH) level above 200 pg/mL were randomly divided into a pulse group and a daily group. They were treated for 20 weeks, with 2 microg oral Alfacalcidol twice weekly or thrice weekly in the pulse group, and 0.5 microg oral Alfacalcidol per day in the daily group. The therapeutic end point was parathyroid hormone level < 200 pg/ mL. The iPTH levels during the study were monitored, and parameters representative of calcium and phosphate metabolism and side effects were also observed. RESULTS: One hundred and fifty-eight patients were initially enrolled, 91 in the pulse therapy group and 67 in the daily therapy group. There was no significant difference in age, hemodialysis duration, proportion of diabetic nephropathy and systemic diseases, proportion of patients who had received active vitamin D therapy previously, mean initial iPTH level (pulse group 570.47 +/- 295.86 pg/mL; daily group 498.33 +/- 207.84 pg/mL), serum calcium, serum phosphate, alkaline phosphatase (AKP), and albumin between two groups. In the pulse therapy group there were more patients with iPTH levels of 500 to approximately 1,000 pg/mL and > 1,000 pg/mL, so stratified analysis according to iPTH level was used. In therapeutic end point, iPTH levels in both groups were significantly lower compared with those before therapy (pulse group 261.29 +/- 234.97 pg/mL, P < .01; daily group 262.17 +/- 274.82 pg/mL, P < .01). After 4 weeks, the ratio of reaching end point in the pulse group was 35.2%, which was significantly higher than that (19.4%) in the daily group (P < .05). More obvious change was seen in the 200 to approximately 500 pg/mL subgroup by stratified analysis (P < .05), whereas there was no significant difference between the 500 to approximately 1,000 pg/mL and > 1,000 pg/mL subgroup (P > .05). At therapeutic end point, the total ratio of reaching end point did not differ between the two groups, and there were no obvious differences between each subgroup. In the iPTH 200 to approximately 500 pg/mL subgroup, mean iPTH%/week in the pulse group was significantly higher than that in the daily group, and no obvious difference was seen in other subgroups. AKP levels decreased significantly in both groups at therapeutic end point (pulse group 98.42 +/- 54.52 vs. 74.21 +/- 30.68 IU/L, P < .01; daily group 103.3 +/- 68.04 vs. 75.40 +/- 34.12 IU/L, P < .01). On the 4th week, AKP level in pulse group (82.39 +/- 35.23 IU/L) was significantly lower than the initial level (98.42 +/- 54.52 IU/L, P < .05), whereas in the daily group there was no difference between each week. The mean serum calcium, phosphate, and [Ca2+] x [P3+] levels in both groups did not change greatly. Nine patients in the pulse group (9.9%) and 8 patients in the daily group (11.9%) suffered hypercalcemia at least once. Persistent hypercalcemia occurred in 8 patients in the pulse group (8.8%) and 9 patients in the daily group (13.4%), but the difference in proportion did not show statistical significance. The serum phosphate in the daily group was higher after the therapy (1.74 +/- 0.36 vs. 1.89 +/- 0.36 mmol/L, P < .05), whereas that in the pulse group remained unchanged. At therapeutic end point, [Ca2+] x [P3+] level in the daily group was higher than that before the therapy (48.04 +/- 11.71 vs. 55.46 +/- 12.66, P < .05), whereas in the pulse group there was no significant difference. Side effects for both groups were minimal and well tolerated. CONCLUSIONS: Alfacalcidol [1alpha-(OH)-D3] has good and safe effects on secondary hyperparathyroidism in maintenance hemodialysis patients. The efficacy and early effects of pulse therapy are superior to those of daily therapy in moderate hyperparathyroidism patients.

[Effects of flavone from leaves of Diospyros kaki on adventitial fibroblasts proliferation by advanced oxidation protein products in vitro].

OBJECTIVE: To observe the effects of flavone from leaves of Diospyros kaki on adventitial fibroblasts proliferation by advanced oxidation protein products (AOPP) in vitro. METHODS: NIH-3T3 cells were cultured in vitro and treated with AOPP and flavone from leaves of Diospyros kaki, respectively, and observed in comparison with the control group. The ratio of cell proliferation was determined by non-radioactive MTS/PES assay. RESULTS: The ratio of cell proliferation was 1.789 +/- 0.299 in the control group, and 2.064 +/- 0.141, 2.149 +/- 0.218, 2.108 +/- 0.165, 2.124 +/- 0.131 and 2.087 +/- 0.125 in AOPP groups corresponding to AOPP concentrations of 100, 50, 10, 1 and 0.1 microg/ml, respectively. It showed that AOPP significantly induced the fibroblasts proliferation when the concentration was above 100 ng/ml (P < 0.05). The ratio of cell proliferation was 1.714 +/- 0.179 in flavone from leaves of Diospyros kaki group corresponding to concentration of 50 microg/ml. It also showed that flavone from leaves of Diospyros kaki alone had no effect on fibroblasts proliferation (P > 0.05). With AOPP stimulation, flavone from leaves of Diospyros kaki significantly inhibited fibroblasts proliferation (P < 0.05). CONCLUSIONS: Flavone from leaves of Diospyros kaki can significantly inhibit the adventitial fibroblasts proliferation stimulated by AOPP in vitro.