Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Salidroside ameliorates pathological cardiac hypertrophy via TLR4-TAK1-dependent signaling.

Salidroside, a prominent active ingredient in traditional Chinese medicines, is garnering increased attention because of its unique pharmacological effects against ischemic heart disease via MAPK signaling, which plays a critical role in regulating the evolution of ventricular hypertrophy. However, the function of Salidroside on myocardial hypertrophy has not yet been elucidated. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with Salidroside (100 mg kg-1  day-1 ) by oral gavage for 3 weeks starting 1 week after surgery. Four weeks after TAC surgery, the mice were subjected to echocardiography and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes were used to validate the protective effects of Salidroside in response to Angiotensin II (Ang II, 1 µM) stimulation. Here, we proved that Salidroside dramatically inhibited hypertrophic reactions generated by pressure overload and isoproterenol (ISO) injection. Salidroside prevented the activation of the TAK1-JNK/p38 axis. Salidroside pretreatment of TAK1-inhibited cardiomyocytes shows no additional attenuation of Ang II-induced cardiomyocytes hypertrophy and signaling pathway activation. The overexpression of constitutively active TAK1 removed the protective effects of Salidroside on myocardial hypertrophy. TAC-induced increase of TLR4 protein expression was reduced considerably in the Salidroside treated mice. Transient transfection of small interfering RNA targeting TLR4 (siTLR4) in cardiomyocytes did not further decrease the activation of the TAK1/JNK-p38 axis. In conclusion, Salidroside functioned as a TLR4 inhibitor and displayed anti-hypertrophic action via the TAK1/JNK-p38 pathway.

Micronutrient Supplementation to Reduce Cardiovascular Risk.

BACKGROUND: Healthy dietary patterns are rich in micronutrients, but their influence on cardiovascular disease (CVD) risks has not been systematically quantified. OBJECTIVES: The goal of this study was to provide a comprehensive and most up-to-date evidence-based map that systematically quantifies the impact of micronutrients on CVD outcomes. METHODS: This study comprised a systematic review and meta-analysis of randomized controlled intervention trials of micronutrients on CVD risk factors and clinical events. RESULTS: A total of 884 randomized controlled intervention trials evaluating 27 types of micronutrients among 883,627 participants (4,895,544 person-years) were identified. Supplementation with n-3 fatty acid, n-6 fatty acid, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate- to high-quality evidence for reducing CVD risk factors. Specifically, n-3 fatty acid supplementation decreased CVD mortality (relative risk [RR]: 0.93; 95% CI: 0.88-0.97), myocardial infarction (RR: 0.85; 95% CI: 0.78-0.92), and coronary heart disease events (RR: 0.86; 95% CI: 0.80-0.93). Folic acid supplementation decreased stroke risk (RR: 0.84; 95% CI: 0.72-0.97), and coenzyme Q10 supplementation decreased all-cause mortality events (RR: 0.68; 95% CI: 0.49-0.94). Vitamin C, vitamin D, vitamin E, and selenium showed no effect on CVD or type 2 diabetes risk. ß-carotene supplementation increased all-cause mortality (RR: 1.10; 95% CI: 1.05-1.15), CVD mortality events (RR: 1.12; 95% CI: 1.06-1.18), and stroke risk (RR: 1.09; 95% CI: 1.01-1.17). CONCLUSIONS: Supplementation of some but not all micronutrients may benefit cardiometabolic health. This study highlights the importance of micronutrient diversity and the balance of benefits and risks to promote and maintain cardiovascular health in diverse populations. (Antioxidant Supplementation in the Prevention and Treatment of Cardiovascular Diseases; CRD42022315165).

Fucoidan Protects against Doxorubicin-Induced Cardiotoxicity by Reducing Oxidative Stress and Preventing Mitochondrial Function Injury.

Doxorubicin (DOXO) is a potent chemotherapeutic drug widely used to treat various cancers. However, its clinical application is limited due to serious adverse effects on dose-dependent cardiotoxicity. Although the underlying mechanism has not been fully clarified, DOXO-induced cardiotoxicity has been mainly attributed to the accumulation of reactive oxygen species (ROS) in cardiomyocytes. Fucoidan, as a kind of sulphated polysaccharide existing in numerous brown seaweed, has potent anti-oxidant, immune-regulatory, anti-tumor, anti-coagulate and anti-viral activities. Here, we explore the potential protective role and mechanism of fucoidan in DOXO-induced cardiotoxicity in mice. Our results show that oral fucoidan supplement exerts potent protective effects against DOXO-induced cardiotoxicity by reducing oxidative stress and preventing mitochondrial function injury. The improved effect of fucoidan on DOXO-induced cardiotoxicity was evaluated by echocardiography, cardiac myocytes size and cardiac fibrosis analysis, and the expression of genes related to cardiac dysfunction and remodeling. Fucoidan reduced the ROS content and the MDA levels but enhanced the activity of antioxidant enzymes GSH-PX and SOD in the mouse serum in a DOXO-induced cardiotoxicity model. In addition, fucoidan also increased the ATP production capacity and restored the levels of a mitochondrial respiratory chain complex in heart tissue. Collectively, this study highlights fucoidan as a potential polysaccharide for protecting against DOXO-induced cardiovascular diseases.

Prognostic Prediction Using the Clinical Data and Ultrasomics-Based Model in Acute Respiratory Distress Syndrome (ARDS) Combined with Acute Kidney Injury (AKI).

Objective: A model was constructed based on clinical and ultrasomics features to predict the prognosis of patients in the respiratory intensive unit (RICU) who had acute respiratory distress syndrome (ARDS) combined with acute kidney injury (AKI). AKI ensues after ARDS in RICU ordinarily. The prognostic prediction tool was further developed on this basis. Methods: We collected clinical and ultrasonic data from 145 patients who had ARDS combined with AKI and received continuous renal replacement therapy (CRRT) in the RICU of Xiangyang Hospital of Traditional Chinese Medicine from March 2016 to November 2019. The patients were divided into the survival group (n = 51) and the death group (n = 94), depending on the treatment outcome. The training set (n = 102) and the testing set (n = 43) were established based on patient data. The clinical and ultrasomics features and the CRRT parameters were compared between the two groups. The influence factors of death were analyzed by logistic regression, and four predictive models were established. The predictive performance of 4 models was compared using the R Software 4.1.3. The decision curve analysis graphs were drawn using the R language to determine the net benefit of each. Result: Univariate analysis was conducted in the training set. The following risk factors for poor prognosis were identified: age, concurrent cancers, sequential organ failure assessment score (SOFA), number of organ dysfunctions, positive cumulative fluid balance at 72 h, time from ICU admission to CRRT, mean arterial pressure, oxygenation index, and gray-level size zone matrix, GLSZM (SumEntropy.239/SmallDependenceHighGrayLevelEmphasis.314/Maximum.327/Variance.338) (P < 0.05). Four models were built based on the above factors: clinical model, CRRT model, ultrasomics-based model, and combination model. Comparison using the MedCalc software indicated that the best predictive performance achieved with the combination model. The decision curve analysis also suggested that the combination model had the highest net benefit. Similar results were reported after validation on the testing set. Conclusion: The prognosis of ARDS patients combined with AKI is usually poor. The combination model based on clinical and ultrasomics features had the highest predictive performance. This model can be used to improve the clinical outcome and prognosis.

Aqueous Extract and Polysaccharide of Aconiti Lateralis Radix Induce Apoptosis and G0/G1 Phase Cell Cycle Arrest by PI3K/AKT/mTOR Signaling Pathway in Mesangial Cells.

Mesangial proliferative glomerulonephritis (MesPGN) is a common renal disease that lacks effective drug intervention. Aconiti Lateralis Radix (Fuzi), a natural Chinese medical herb, is found with significant therapeutic effects on various diseases in the clinic. However, its effects on MesPGN have not been reported. This study is aimed to discuss the therapeutic effects of the aqueous extract of Aconiti Lateralis Radix (ALR) and the polysaccharides of Aconiti Lateralis Radix (PALR) on MesPGN as well as the underlying mechanism. In this study, we, firstly, studied the anti-MesPGN mechanism of ALR and PALR. ALR and PALR inhibit the proliferation of the mesangial cells through the PI3K/AKT/mTOR pathway, induce the G0/G1 phase of block and apoptosis, inhibit the activity of Cyclin E and CDK2, increase the expression of Bax, cleaved caspase-8/caspase-8, and cleaved caspase-3/caspase-3 proteins, and effectively inhibit the growth of the mesangial cells. Overall, our data suggest that ALR and PALR may be potential candidates for MesPGN and that PALR is more effective than ALR.

Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials.

Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.

Effects of dietary polyphenol supplementation on iron status and erythropoiesis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The iron-chelating activities of polyphenols raise concern whether there is a risk of iron deficiency or anemia induced by polyphenol supplementation. Results from clinical trials regarding the effects of polyphenol supplementation on iron status and erythropoiesis are inconclusive. OBJECTIVE: We performed a systematic review and meta-analysis of randomized controlled trials to determine the effects of polyphenol supplementation on iron status and erythropoiesis. METHODS: Published articles were searched between May 1988 and 7 December, 2020. Finally, we identified 34 randomized controlled trials. Random-effects meta-analyses were performed to obtain the weighted mean difference of serum iron (SI), transferrin saturation (TS), ferritin, and hemoglobin concentration. Funnel plots and Egger's test were used to determine the risk of bias. The robustness of the effect sizes was examined by sensitivity analysis. RESULTS: Polyphenol supplementation had an inhibitory effect on the SI concentration (-13.72 µg/dL; 95% CI: -20.74, -6.71) and TS (-3.10%; 95% CI: -4.93, -1.27), with no effect on ferritin (-9.34 ng/mL; 95% CI: -28.55, 9.87). Polyphenols increased the hemoglobin concentration (8.53 g/L; 95% CI: 3.33, 13.73). In healthy participants, polyphenol reduced the TS (-3.83%; 95% CI: -7.47, -0.19) and increased the hemoglobin concentration (12.87 g/L; 95% CI: 1.61, 24.14). Similarly, polyphenol reduced the SI concentration (-8.60 µg/dL; 95% CI: -16.10, -1.10) and increased the hemoglobin concentration (8.50 g/L; 95% CI: 0.86, 16.15) in patients with metabolic diseases. In patients with ß-thalassemia, polyphenol decreased the SI concentration (-23.19 µg/dL; 95% CI: -35.84, -10.55), TS (-3.23%; 95% CI: -5.54, -0.91), and ferritin concentration (-223.62 ng/mL; 95% CI: -359.32, -87.91), but had no effect on the hemoglobin concentration. CONCLUSION: Healthy individuals and patients with metabolic diseases may benefit from the positive impact of polyphenols on erythropoiesis. Patients with ß-thalassemia may benefit from the effect of polyphenols on reducing SI. This trial was registered at PROSPERO (International prospective register of systematic reviews) as CRD42020161983.

6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway.

6-Gingerol, a pungent ingredient of ginger, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of 6-gingerol on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of 6-gingerol on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms. C57BL/6 mice were subjected to transverse aortic constriction (TAC), and treated with 6-gingerol (20 mg/kg, ig) three times a week (1 week in advance and continued until the end of the experiment). Four weeks after TAC surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of 6-gingerol in response to phenylephrine (PE) and transforming growth factor-ß (TGF-ß) challenge. We showed that 6-gingerol administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in TAC mice. In the in vitro study, we showed that treatment with 6-gingerol (20 µM) blocked PE-induced-cardiomyocyte hypertrophy and TGF-ß-induced cardiac fibroblast activation. Furthermore, 6-gingerol treatment significantly decreased mitogen-activated protein kinase p38 (p38) phosphorylation in response to pressure overload in vivo and extracellular stimuli in vitro, which was upregulated in the absence of 6-gingerol treatment. Moreover, transfection with mitogen-activated protein kinase kinase 6 expressing adenoviruses (Ad-MKK6), which specifically activated p38, abolished the protective effects of 6-gingerol in both in vitro and in vivo models. In conclusion, 6-gingerol improves cardiac function and alleviates cardiac remodeling induced by pressure overload in a p38-dependent manner. The present study demonstrates that 6-gingerol is a promising agent for the intervention of pathological cardiac remodeling.

[Effect of electroacupuncture at different stages on the expression of Fas and FasL in brain tissue of rats with traumatic brain injury].

OBJECTIVE: To investigate the expression of apoptosis-related proteins Fas and FasL in the brain tissue of rats with traumatic brain injury and the effect of electroacupuncture on the expression of Fas and FasL, so as to explore the effective time window of electroacupuncture in the treatment of traumatic brain injury. METHODS: Sprague-Dawley rats were randomly divided into blank group, sham-operation group, model group, and electroacupuncture treatment groups 1, 2, and 3. Traumatic brain injury was induced by the modified Feeney free-fall impact device, and for the rats in the electroacupuncture treatment groups 1, 2, and 3, electroacupuncture started at 4 hours and on days 3 and 7, respectively, after modeling and lasted to day 14. The Morris water maze test was used to evaluate learning and memory ability, and immunofluorescence assay and Western blot were used to observe the changes in the expression of Fas and FasL in traumatic brain tissue. RESULTS: Compared with the blank group and the sham-operation group, the model group had a lower percentage of time spent in the target quadrant from the 3rd day folowing modeling; after electroacupuncture intervention, the electroacupuncture treatment groups showed a gradual increase in the time spent in the target quadrant, and on day 7,10 and 14, electroacupuncture treatment group 1 had a significantly higher percentage than the model group (P<0.05). On day 14, electroacupuncture treatment group 2 had a significantly higher percentage than the model group (P<0.05). After electroacupuncture intervention, all groups except the blank group and the sham-operation group had increases in the expression of Fas and FasL in brain tissue, which reached the highest level on day 7 after modeling and then tended to decrease; compared with electroacupuncture treatment groups 2 and 3 and the model group, electroacupuncture treatment group 1 had significant reductions in the expression of Fas and FasL (P<0.05, P<0.01); compared with electroacupuncture treatment group 3 and the model group, electroacupuncture treatment group 2 had significant decreases in the expression of Fas and FasL (P<0.05) on day 14 after modeling; compared with the model group, electroacupuncture treatment group 3 had significant reductions in the expression of Fas and FasL in brain tissue on day 14 after modeling (P<0.05). CONCLUSION: Early electroacupuncture intervention can regulate the apoptosis receptor pathway by down-regulating Fas and FasL to exert a therapeutic effect on traumatic brain injury and help with the recovery of cognition and memory ability after traumatic brain injury.

Wenyang Huazhuo Fang exerts transient receptor potential cation channel subfamily C member-dependent nephroprotection in a rat model of doxorubicin-induced nephropathy.

OBJECTIVE: To determine the effect of Wenyang Huazhuo Fang (WHF), a Traditional Chinese Medicine decoction, on renal function in a rat model of doxorubicin-induced nephropathy, and to elucidate the underlying mechanism. METHODS: Sprague-Dawley rats were randomly divided into six groups: control, doxorubicin-nephropathy, and prednisone-treated (6.45 mg·kg-1·d－1) doxorubicin nephropathy groups, as well as high- (7.26 g·kg-1·d－1, medium- (2.42 g·kg-1·d－1, and low-dose (0.81 g·kg-1·d－1 WHF-treated doxorubicin-nephropathy groups. The nephropathy rat model was established by two tail vein injections of doxorubicin, followed by prednisone or WHF treatment for 8 weeks. Body weights were monitored and urinary protein was measured every 2 weeks. After the end of the treatment period, the rats were euthanized. Serum biochemical indicators were determined and renal morphological alterations were assessed using histological staining. The expression of transient receptor potential cation channel subfamily C member 6 (TRPC6), stromal interaction molecule 1 (STIM1), and calcium release-activated calcium channel protein 1 (Orai1) was detected using western blotting, and their mRNA levels were examined using quantitative real-time reverse transcription-polymerase chain reaction. RESULTS: WHF treatment was found to significantly ameliorate weight loss, proteinuria, hypoalbuminemia, and dyslipidemia in doxorubicin-nephropathy rats. The protein and mRNA levels of TRPC6, STIM1, and Orai1 were partially, but significantly suppressed by prednisone or WHF treatment. CONCLUSION: Treatment with WHF significantly ameliorates renal injury in a rat model of doxorubicin-induced nephropathy, which could be at least partially related to repression of the TRPC6 pathway.

Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms.

Iron homeostasis is essential for health; moreover, hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia. Here, we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells. We validated the results in C57BL/6J mice and a mouse model of hemochromatosis (Hfe-/- mice). Our screen revealed that the anti-rheumatoid arthritis drug auranofin (AUR) potently upregulates hepcidin expression. Interestingly, we found that canonical signaling pathways that regulate iron, including the Bmp/Smad and IL-6/Jak2/Stat3 pathways, play indispensable roles in mediating AUR's effects. In addition, AUR induces IL-6 via the NF-κB pathway. In C57BL/6J mice, acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation. Whereas chronically treating male Hfe-/- mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling, decreasing systemic iron overload, but less effective in females. Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells, providing a mechanistic explanation for ineffectiveness of AUR in female Hfe-/- mice. Notably, high-dose AUR (25 mg/kg) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity. We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by high-dose AUR without comprising its beneficial effect on iron metabolism. In conclusion, our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.

Substrate Metabolism-Driven Assembly of High-Quality CdS xSe1- x Quantum Dots in Escherichia coli: Molecular Mechanisms and Bioimaging Application.

Biosynthesis offers opportunities for cost-effective and sustainable production of semiconductor quantum dots (QDs), but is currently restricted by poor controllability on the synthesis process, resulting from limited knowledge on the assembly mechanisms and the lack of effective control strategies. In this work, we provide molecular-level insights into the formation mechanism of biogenic QDs (Bio-QDs) and its connection with the cellular substrate metabolism in Escherichia coli. Strengthening the substrate metabolism for producing more reducing power was found to stimulate the production of several reduced thiol-containing proteins (including glutaredoxin and thioredoxin) that play key roles in Bio-QDs assembly. This effectively diverted the transformation route of the selenium (Se) and cadmium (Cd) metabolic from Cd3(PO4)2 formation to CdS xSe1- x QDs assembly, yielding fine-sized (2.0 ± 0.4 nm), high-quality Bio-QDs with quantum yield (5.2%) and fluorescence lifetime (99.19 ns) far exceeding the existing counterparts. The underlying mechanisms of Bio-QDs crystallization and development were elucidated by density functional theory calculations and molecular dynamics simulation. The resulting Bio-QDs were successfully used for bioimaging of cancer cells and tumor tissue of mice without extra modification. Our work provides fundamental knowledge on the Bio-QDs assembly mechanisms and proposes an effective, facile regulation strategy, which may inspire advances in controlled synthesis and practical applications of Bio-QDs as well as other bionanomaterials.

Artemisinin ameliorated proteinuria in rats with adriamycin-induced nephropathy through regulating nephrin and podocin expressions.

OBJECTIVE: To investigate the effects of artemisinin against proteinuria and glomerular filtration barrier damage in rats with adriamycin-induced nephropathy, and the potential mechanism underpinned the action. METHODS: Forty adriamycin rats were randomly divided into two groups with the ratio of 1 : 3; the small-number group served as control group (n = 10), and the rats in the large-number group were treated with adriamycin to induce nephropathy; then they were further randomly assigned into 3 subgroups: benazepril group (n = 10), artemisinin group (n = 10), and adriamycin group (n = 10). The benazepril group and artemisinin group were treated with benazepril suspl (5.0 mg/kg daily) and artemisinin suspl (150 mg/kg daily) respectively after being modeled; those in the control group and adriamycin group were intragastrically administered an equivalent volume of distilled water every day. The treatment after model establishment lasted for a total of 4 weeks. The 24 h uric protein, blood biochemicals, renal pathological changes, renal ultrastrutural changes, Nephrin and Podocin proteins and gene expressions were measured by Coomassie brilliant blue assay, completely automatic biochemical analyzer, light microscope, electron microscopy, Western blot and reverse transcription polymerase chain reaction, respectively. RESULTS: The rats in adriamycin group showed a significant increase in 24 h uric protein excretion, serum total cholesterol (TC), triglyceride (TG), blood urea nitrogen (BUN), serum creatinine (Scr) and decrease in albumin (Alb) (P < 0.05 or P < 0.01). Compared with adriamycin group, artemisinin could reduce uric protein excretion, decrease the serum TC, TG elevation, increase the serum Alb level, up-regulate the expressions of Nephrin and Podocin (P < 0.05 or P < 0.01), but no statistical significance effects on the levels of BUN, Scr in artemisinin group (P > 0.05). The renal pathological and ultrastrutural observation indicate that artemisinin could attenuate the severity of foot process effacement and fusion in the nephropathic rats. CONCLUSION: Artemisinin might have an effect on the nephropathy in rats caused by adriamycin, which may be at least partly correlated with attenu- ation of the severity of foot process effacement and fusion, up-regulation of the expressions of Nephrin and Podocin in the glomeruli in the rats.

"Qufeng Tongluo" acupuncture prevents the progression of glomerulonephritis by decreasing renal sympathetic nerve activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Although the exact mechanism(s) underlying acupuncture remain unknown, acupuncture and acupuncture-like somatic nerve stimulation have been used to treat different kidney diseases and several complications related to them.The aim of this preliminary study was to assess the effectiveness of acupuncture on glomerulonephritis (GN) according to the theory of "Wind-hided renal collaterals" previously proposed. MATERIAL AND METHODS: We used a New Zealand white rabbit model of cationized bovine serum albumin (cBSA)-induced glomerulonephritis and then administered them metoprolol, irbesartan or acupuncture to evaluate the effectiveness of acupuncture treatment and preliminarily explore its potential mechanism. RESULTS: After immunization, our results showed that compared to the cBSA+MET and cBSA+IRB medication groups, "Qufeng Tongluo" significantly lowered parameters of renal function and improved podocyte injury in the 3rd, 6th and 8th weeks of treatment. Moreover, acupuncture increased the protein expression of phosphorylated ERK1/2. CONCLUSIONS: Our study suggests that a potential mechanism by which acupuncture has an antihypertensive effect and can significantly halt deteriorating renal function due to cBSA GN might be mediated by inhibiting the Erk1/2 MAPK pathway to reduce renal sympathetic nerve activity (RSNA).

[Effect of Qufeng Tongluo Recipe on the expressions of connexin 36 protein and gene in rat mesangial cells].

OBJECTIVE: To determine the effect of Qufeng Tongluo Recipe (QFTLR) on the expressions of connexin 36 (Cx36) protein and gene in rat mesangial cells (MCs) and the proliferation of the MCs. METHODS: Serum samples containing Benazepril (Bena) and QFTLR were prepared in line with serum pharmacology methodology. The MCs cultured in vitro were divided into normal control and Lipopolysaccharide (LPS), Bena and QFTLR treated groups. The expressions of Cx36 protein and gene were detected by laser scanning confocal microscope (LSCM), Western blot, immunohistochemical assay and quantitative real time polymerase chain reaction (QRT-PCR) respectively. RESULTS: Compared with the control, higher level of Cx36 protein expression was found in the MCs than treated with LPS (P < 0.01). Both Bena and QFTLR lowered the level of Cx36 protein expression in the MCs treated with LPS significantly (P < 0.01 or P < 0.05). Similar results were found with the expression of Cx36 mRNA. CONCLUSION: QFTLR inhibits the proliferation of rat MCs, possibly through down-regulating the expressions of Cx36 protein and gene.

Black soyabean seed coat extract regulates iron metabolism by inhibiting the expression of hepcidin.

Hepcidin, a key regulator of Fe homeostasis, is an ideal drug target for treating patients with Fe disorders such as haemochromatosis, anaemia of chronic inflammation and Fe-deficiency anaemia. However, whether (and how) traditional Chinese black foods (e.g., black soyabeans) target hepcidin and improve Fe-deficiency anaemia remains unclear. Herein, we report that black soyabean seed coat extract (BSSCE) can potently inhibit the in vitro and in vivo expression of hepcidin. In the present study, in cells treated with 200 µg/ml BSSCE, hepcidin expression was found to be reduced to only 6% of the control levels (P<0.01). An AIN-76A diet containing 2% BSSCE was fed to 8-week-old male C57BL/6 mice for 0, 1, 7, 15 or 30 d; importantly, compared with the day 0 group, the day 7 group exhibited nearly a 50% decrease in hepatic hepcidin expression (P<0.01), a 35% decrease in splenic Fe concentrations (P<0.05) and a 135% increase in serum Fe concentrations (P<0.05). Mechanistically, the effect of BSSCE on hepcidin expression was mediated via a reduction in the phosphorylation levels of mothers against decapentaplegic homolog proteins (Smad)1/5/8. Consequently, the mice in the day 30 group exhibited large increases in erythrocyte counts (111% v. day 0, P<0.01), Hb concentrations (109%, P<0.01) and haematocrit values (108%, P<0.01). In conclusion, these results indicate that black soyabean extract regulates Fe metabolism by inhibiting the expression of hepcidin. This finding can be used to optimise the intervention of patients with hepcidin-related diseases, including Fe-deficiency anaemia.

Qufeng Tongluo Prescription () inhibits mesangial cell proliferation and promotes apoptosis through regulating cell cycle progression.

OBJECTIVE: To study the effects and possible underlying mechanism of Qufeng Tongluo Prescription (, QFTL) on the regulation of mesangial cells (MCs) proliferation and apoptosis. METHODS: The MCs used in this experiment have undergone five passages induced by lipopolysaccharide (LPS). Changes in the proliferation, apoptosis, cell cycle regulatory proteins and mRNA expression levels of the MCs after administration of Benazepril or QFTL were measured by methyl thiazolyl tetrazolium (MTT) reduction assay, flow cytometry, Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. RESULTS: The addition of Benazepril or QFTL serum inhibited LPS-induced MC proliferation after treatment for 24, 48 and 72 h, respectively (P<0.05 or P<0.01). Moreover, the inhibitory effect is more significant in the QFTL group at 48 h (P<0.05). Compared with the control group, LPS-induced cell proliferation decreased the number of cells in G1 phase versus cells in S and G2/M phases, while the addition of QFTL and Benazepril serum increased the ratio of cells at G1 phase (P<0.05 or P<0.01) to cells at S phase (P<0.01), implicating the cell cycle inhibition effect exerted by QFTL. LPS decreased the level of MC apoptosis, compared with the control group (P<0.05), while QFTL and Benazepril serum increased the level of MC apoptosis (P<0.01). Moreover, the difference between the QFTL group and the Benazepril group was statistically significant (P<0.01). Compared with the control group, the protein and mRNA expression levels of cylinD1, cyclin dependent kinase 2 (CDK2) and p21 were significantly increased (P<0.05 or P<0.01), p27 was decreased but with no statistical significance (P>0.05); After being treated with QFTL and Benazepril serum, the protein and mRNA expression levels of cylinD1, CDK2, p21 were decreased and p27 increased significantly (P<0.05 or P<0.01); Compared with the Benazepril group, QFTL show better effects on protein and mRNA expression levels of cylinD1, CDK2 (P<0.05 or P<0.01) and p21 protein expression (P<0.05). CONCLUSION: QFTL inhibits MCs proliferation, promotes MCs apoptosis through an underlying mechanism of down-regulating the protein and mRNA expression levels of cylinD1, CDK2, p21 and up-regulation of the expression level of p27.

Baicalein inhibits the invasion and metastatic capabilities of hepatocellular carcinoma cells via down-regulation of the ERK pathway.

Baicalein, a widely used Chinese herbal medicine, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain poorly understood. Therefore, the purpose of this study was to assess the anti-metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays utilized in both HCC cell lines and in an animal model, we found that baicalein inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after treatment with baicalein for 24 hours, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen activator (u-PA) expression as well as proteinase activity in hepatocellular carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent fashion. Moreover, baicalein treatment dramatically decreased the levels of the phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked the anti-metastatic effects of baicalein. Combined treatment with an ERK inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP-9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the invasive capabilities of MHCC97H cells were also inhibited. In conclusion, baicalein inhibits tumor cell invasion and metastasis by reducing cell motility and migration via the suppression of the ERK pathway, suggesting that baicalein is a potential therapeutic agent for HCC.

Traditional herbal medicine: a review of potential of inhibitory hepatocellular carcinoma in basic research and clinical trial.

Although significantly develops in hepatocellular carcinoma (HCC), features of HCC remain an aggressive cancer with a dismal outcome. Traditional Chinese medicine (TCM), specifically Chinese herbal medicine (CHM), is one of the most popular complementary and alternative medicine modalities worldwide. The use of heat-clearing and detoxicating (Chinese named qingre jiedu) CHM has attracted great attention as an alternative antitumor including HCC considering its low toxicity and high activity. Together these reports indicate that CHM is a promising anti-HCC herbal remedy in basic research. For patients with advanced HCC, CHM including formula and single combined with transcatheter arterial chemoembolization or chemotherapy is able to decrease tumor growth and the side effect of toxicity and improve overall survival, quality of life, and immune function. Due to its abundance, low cost, and safety in consumption, CHM remains a species with tremendous potential for further investigation in HCC.