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Biomedical subjects

Haiyan Wang

Publications and source records attributed to Haiyan Wang.

At least 37 records · Page 2Linked to original sources

Chinese herbal medicine in the treatment of chronic kidney disease.

Chronic kidney disease (CKD) is a worldwide public health issue with poor outcomes and high cost. There is growing evidence that some of the adverse outcomes of CKD can be prevented or delayed by early treatment using angiotensin II-converting enzyme inhibitors and angiotensin II-receptor blockers. A great amount of the world's population has been using traditional Chinese herbal medicine (TCHM) for treatment of CKD and has accumulated their experience for years. In this article, the knowledge and the therapeutic principles of traditional Chinese medicine in the treatment of CKD are briefly reviewed. The efficacy of several TCHMs, supported by either clinical evidence or experimental studies, is presented. The future direction for the study of Chinese herbal medicines in CKD is discussed.

Angelica↗

The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.

Animals↗

Does chasing selected 'Fox' to the nucleus prevent diabetes?

Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates gene expression in the liver, pancreatic islets and adipocytes. It is required for the maintenance of glucose and lipid homeostasis. Hyperinsulinemia-mediated inactivation of Foxa2 by nuclear exclusion has recently been implicated in the development of liver steatosis and insulin resistance in three animal models of diabetes. These abnormalities were cured by adenovirus-mediated expression of a constitutively active form of Foxa2 containing a mutated T156 phosphorylation site, which increases fatty acid oxidation and reduces its biosynthesis. Accordingly, the prevention of phosphorylation of Foxa2 was suggested as a pharmacological target for the treatment of obesity and diabetes.

Animals↗

A report with consensus statements of the International Society of Nephrology 2004 Consensus Workshop on Prevention of Progression of Renal Disease, Hong Kong, June 29, 2004.

This report summarizes the discussions of the International Society of Nephrology (ISN) 2004 Consensus Workshop on Prevention of Progression of Renal Disease, which was held in Hong Kong on June 29, 2004. Three key areas were discussed during the workshop: (1) screening for chronic kidney disease; (2) evaluation and estimating progression of chronic kidney disease; and (3) measures to prevent the progression of chronic kidney disease. Fifteen consensus statements were made in these three areas, as endorsed by the participants of the workshop. The ISN can make use of and take reference to these statements in formulating its policy for tackling chronic kidney disease, a disease with significant global impact.

Hong Kong↗

Prevention of the progression of chronic kidney disease: practice in China.

With the epidemic rise of end-stage renal disease (ESRD) in many countries of the world, there is an urgent need to develop and implement strategies aiming at preventing the development and progression of chronic kidney disease (CKD), and the situation is the same in China. Glomerulonephritis is still the most common cause of ESRD in China; however, epidemiologic studies have revealed that the prevalence of diabetes and hypertension, which both are major causes of ESRD in many developed countries, are increasing dramatically. Additional studies about the prevalence of albuminuria in diabetes mellitus (DM) patients, and the prevalence of kidney lesion in certain high-risk population (e.g., hypertension and atherosclerosis) are undergoing. According to a questionnaire survey and some reports, education program for Chinese nephrologists and practitioners should to be strengthened.

China↗

periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype.

Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (peri(lacZ)) embryos are grossly normal. Postnatally, however, approximately 14% of the nulls die before weaning and all of the remaining peri(lacZ) nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the peri(lacZ) nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses.

Animals↗

Adrenomedullin impairs the profibrotic effects of transforming growth factor-beta1 through recruiting Smad6 protein in human renal tubular cells.

Adrenomedullin (AM) was originally identified as a vasodilator peptide, and has recently been shown to be an antiproliferative factor in renal mesangial cells, suggesting that adrenomedullin may impair the progression of glomerulosclerosis. This study was to investigate the effect of adrenomedullin on transforming growth factor-beta1 (TGF-beta1)-stimulated cell growth, synthesis of extracellular matrix (ECM) components and the related molecular mechanism in a human tubular epithelial cell line HK-2. TGF-beta1 inhibited cell proliferation induced by fetal bovine serum, but neither AM itself affectted cell proliferation, nor did AM influence TGF-beta1-caused cell growth arrest. However, AM beginning at 10(-8) M alleviated the action of TGF-beta1-stimulated cellular collagen synthesis and secretion of fibronectin into cell culture supernatant. Activation of Smad proteins is known to be the key signaling pathway of the profibrotic effect of TGF-beta1, AM at 10(-8) M exerted no effect on TGF-beta1-induced Smad2 phosphorylation, but prevented the suppression of the inhibitory Smad6 protein by TGF-beta1 and restored Smad2-Samd6 complex formation. Our results suggest that AM can attenuate TGF-beta1-mediated renal tubulointerstitial ECM turnover via an antagonistic mechanism of inhibitory Smad in TGF-beta1-elicited signaling.

Adrenomedullin↗

A new initiative in nephrology: 'Kidney disease: improving global outcomes'.

The burden of kidney disease: Improving global outcomes. Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence of patients requiring replacement therapy. There is an even higher prevalence of patients in earlier stages of CKD, with adverse outcomes such as kidney failure, cardiovascular disease, and premature death. Patients at earlier stages of CKD can be detected through laboratory testing and their treatment is effective in slowing the progression to kidney failure and reducing cardiovascular events. The evidence-based care of these patients are universal and independent of their geographic location. This paper describes the need to develop a uniform and global public health approach to the worldwide epidemic of CKD. It is to this end that a new initiative Kidney Disease: Improving Global Outcomes' has been established. Some current and future activities of this initiative are described. They include among others modification of the classification of CKD, the development of guidelines on hepatitis C, the organisation of consensus conferences like on Renal Osteodystrophy, and the creation of a website allowing the comparison of the five main English language clinical practice guidelines in kidney disease worldwide.

Chronic Disease↗

ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta1 stimulated glomerular podocytes.

The unregulated synthesis of glomerular basement membrane (GBM) components, extracelluar matrix (ECM) proteins, or the secretion of ECM-degradation enzymes, matrix metalloproteinases (MMPs), by podocytes under pathological conditions might be major factors in GBM damage. The present study examined the effects and the underlying molecular mechanism of transforming growth factor beta1 (TGFbeta1) on the production of gelatinase in cultured murine podocytes. Our results showed that TGFbeta1 is the most potent inducer of MMP-9 secretion in both a dose- and time-dependent manner, but has very little effect on MMP-2 secretion. TGFbeta1 upregulated MMP-9 mRNA levels, but did not affect the expression of matrix mettaloproteinases TIMP-1 mRNA. TGFbeta1 induced activation of both Smad2 and extracellular signal-regulated kinases (ERK1/2). However, blockade of Smad2 signaling pathway by Staurosporine did not affect the TGFbeta1-stimulated secretion of MMP-9, whereas inhibition of activation of ERK1/2 by PD98059 abolished TGFbeta1-stimulated secretion of MMP-9 and expression of MMP-9 mRNA. Protein levels of the transcriptional factor Ets-1 increased and were sustained for 12 h by TGFbeta1-stimulation. Our data also showed that blockage of ERK1/2 activation by PD98059 led to a reduction in the level of Ets-1 protein and to a consequent decrease in MMP-9 mRNA levels. These results demonstrate that TGFbeta1 can induce the production of MMP-9 in podocytes through the ERK1/2 MAPK pathway, and suggested that an increase in MMP-9 enzymatic activities may be involved in the damage of the GBM in response to inflammatory factors, ultimately leading to glomerulosclerosis.

Animals↗

Tyrosine phosphorylation of the LDL receptor-related protein (LRP) and activation of the ERK pathway are required for connective tissue growth factor to potentiate myofibroblast differentiation.

Renal myofibroblasts play a crucial role in the accumulation of excess extracellular matrix during renal fibrosis. Both transforming growth factor-beta1 (TGFbeta1) and connective tissue growth factor (CTGF) are important profibrotic growth factors, which interact in the pathogenesis of fibrosis. In this study, we demonstrate that CTGF alone has no influence on myofibroblast transformation and fibronectin secretion in kidney interstitial fibroblasts, whereas incubation of CTGF in combination with TGFbeta1 enhanced TGFbeta1 responses, including myofibroblast activation, de novo expression of alpha-SMA, and extracellular accumulation of fibronectin. CTGF induced tryrosine phosphorylation of the cytoplasmic domain of the low-density lipoprotein receptor-associated protein (LRP) in fibroblasts, and the LRP-antagonist, receptor-associated protein (RAP) inhibited CTGF-induced tryrosine phosphorylation of LRP. Inhibition of LRP signaling reduced CTGF-mediated synergistic induction of alpha-SMA protein. Furthermore, the potentiating action of CTGF was neither dependent on modulation of TGFbeta1-induced Smad2 phosphorylation and its association with Smad4, nor did it result from nuclear accumulation of activated Smad2. When TGFbeta1-pretreated fibroblasts were incubated with CTGF, activation of ERK1/2 MAPK signaling was observed. Inhibition of ERK activation by the MEK1 inhibitor PD98059 was associated with a reduction of CTGF-promoted alpha-SMA protein expression. Our in vitro studies provide evidence that CTGF potentiates TGFbeta1-mediated myofibroblast differentiation and activates differentiated myofibroblasts.

Actins↗

Molecular modeling of B-DNA site recognition by Ru intercalators: molecular shape selection.

In this work, molecular modeling methods have been applied to the interaction characterization of polypyridyl transitional-metal complexes with the oligonucleotide (B-DNA fragment). In order to explore the factors governing the groove recognition and intercalative depth, we establish a simple and practical docking method (step-by-step docking operation) to obtain potential curves while making complexes inset into B-DNA along an assigned path. Energy values in the potential curve are obtained from energy minimization of binding geometries. Modeling results clearly show that the optimum binding conformation corresponding to the global minimum in the potential curve for each complex is found to correlate well with the experimental results. Our results also confirm that minor changes of the ligand structure can lead to profound influences on binding geometries, so the molecular shape of the complexes is a predominant factor in governing the binding mode. Moreover, we find that the vdW force and "water molecular effect" are strongly associated with molecular-shape selection in our model. These results complement and extend the knowledge of the nature of these complexes binding to B-DNA.

Computer Simulation↗

Antifibrotic effect of the Chinese herbs, Astragalus mongholicus and Angelica sinensis, in a rat model of chronic puromycin aminonucleoside nephrosis.

UNLABELLED: Nephrotic syndrome has long been treated in China with two herbs, Astragalus mongholicus and Angelica sinensis, which may have antifibrotic effects. METHODS: Rats with chronic puromycin-induced nephrosis were treated with Astragalus and Angelica 3 mL/d (n = 7) or enalapril 10 mg/kg/d (n = 7). Normal control rats (n = 7) received saline rather than puromycin, and an untreated control group (n = 7) received puromycin but no treatment. After 12 weeks, stained sections of the glomerulus and tubulointerstitium were evaluated for injury. Immunohistochemistry staining measured extracellular matrix components, transforming growth factor-beta1 (TGFbeta1), osteopontin, ED-1-positive cells, and alpha-actin. TGFbeta1 mRNA was assessed by in situ hybridization. Renin, ACE activity, angiotensin, and aldosterone were measured by radioimmunoassay or colorimetry. In the untreated rats, chronic renal injury progressed to marked fibrosis at 12 weeks. Astragalus and Angelica significantly reduced deterioration of renal function and histologic damage. Expressions of type III and IV collagen, fibronectin, and laminin also decreased significantly. This anti-fibrotic effect was similar to that of enalapril. The herbs had no effect on the renin-angiotensin system but did reduce the number of ED-1-positive, and alpha-actin positive cells and expression of osteopontin compared to untreated controls. The combination of Astragalus and Angelica retarded the progression of renal fibrosis and deterioration of renal function with comparable effects of enalapril. These effects were not caused by blocking the intrarenal renin-angiotensin system, but associated with suppression of the overexpression of TGFbeta1 and osteopontin, reduction of infiltrating macrophages, and less activation of renal intrinsic cells [corrected].

Angelica sinensis↗

Photocatalysis enhancement by electric field: TiO2 thin film for degradation of dye X-3B.

According to the theory of photocatalysis, the efficiency of photocatalysis decreases mostly due to the recombination of photo-generated electron-hole pairs. An electric field across a photocatalyst can promote the separation of photo-generated electrons and holes and prevent them from recombination so as to enhance the efficiency of photocatalysis. And the synergetic decomposition efficiency of photocatalysis and an electric field is greater than that of the simple combine of their single efficiency. The performance of photocatalysis enhanced by electric field (PEEF) and operating conditions such as the direction of the electric field, the voltages between the two electrodes, the material of the electrodes, which may affect the efficiency of PEEF, were investigated in this paper. The results indicate that the system of PEEF abides the established theory of photocatalysis.

Catalysis↗

Anti-inflammatory effect of PPARgamma in cultured human mesangial cells.

Our aim is to investigate whether peroxisome proliferator-activator receptor-gamma (PPARgamma) expression was altered in human mesangial cells under inflammatory stress and whether PPARgamma could retard the inflammatory responses. Based on cultured human mesangial cell lines (HMCLs), PPARgamma expressions at protein and mRNA levels were observed by Western blot analysis and reverse transcriptase polymerase chain reaction. Informatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay. Our results demonstrated that PPARgamma protein expression was dramatically increased in HMCLs stimulated by IL-1beta (10 ng/mL). The levels of IL-6 and TNF-alpha in HMCL supernatants, protein, and mRNA expressions of PPARgamma in IL-1beta challenge cells were significantly increased more than those in untreated cells. Importantly, PPARgamma agonists troglitazone, rosiglitazone, and 15-deoxy-delta(12, 14)-prosglandin J2 significantly decreased the up expression of TNF-alpha and IL-6 in HMCL supernatants stimulated by IL-1beta. Furthermore, troglitazone downregulated TNF-alpha and IL-6 mRNA expression from IL-1beta challenge HMCLs. Our data suggest that PPARgamma plays an important role in mesangial cells responding to inflammatory stress. PPARgamma may prove to be a pharmacological target in glomerulonephritis.

Anti-Inflammatory Agents↗

The burden of kidney disease: improving global outcomes.

Chronic kidney disease (CKD) is a worldwide public health problem. There is an increasing incidence and prevalence of patients with kidney failure requiring replacement therapy, with poor outcomes and high cost. There is an even higher prevalence of patients in earlier stages of CKD, with adverse outcomes such as kidney failure, cardiovascular disease, and premature death. Patients at earlier stages of CKD can be detected through laboratory testing and their treatment is effective in slowing the progression to kidney failure and reducing cardiovascular events. The science and evidence-based care of these patients are universal and independent of their geographic location. There is a clear need to develop a uniform and global public health approach to the worldwide epidemic of CKD. It is to this end that a new initiative "Kidney Disease: Improving Global Outcomes" has been established. Its stated mission is "Improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines."

Global Health↗

Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study.

Mycophenolate mofetil (MMF) is a potential new treatment for diffuse proliferative lupus nephritis. This study examines the clinical and histopathological effects, and potential mechanisms, of combination MMF/prednisone therapy in diffuse proliferative lupus nephritis. Nine patients with diffuse proliferative lupus nephritis confirmed by renal biopsy received MMF/prednisone for six months when repeat biopsies were performed. Clinical and histopathological parameters of activity and chronicity were studied. Collagens were detected by Sirus red staining; leucocyte phenotype, osteopontin (OPN), fibrinectin (FN), alpha-smooth muscle actin (alpha-SMA) and TGF-beta1 were detected by immunohistochemistry. The changes of clinical and histopathologic parameters were assessed and compared to histopathologic indicators. Eight of the nine patients achieved clinical remission; renal function deteriorated in one. Histopathological activity indices reduced significantly (9.56 +/- 2.83 versus 5.22 +/- 1.86, P < 0.01); however, the chronicity indices did not change (3.56 +/- 1.42 versus 3.22 +/- 1.20). T-cell and monocyte/macrophage infiltration. OPN expression and the percentage of proliferative cells in both glomerulus and tubulo-interstitium decreased significantly. Other features of chronic lesions, except for glomerular collagen deposition, did not change. In conclusion, MMF/prednisone therapy was effective for our patients with proliferative lupus nephritis. The active inflammatory lesions could be ameliorated through reduction of lymphocyte and monocyte/macrophage infiltration, inhibition of cell proliferation and downregulation of adhesive molecules. However, the chronic fibrotic lesions could not be significantly reduced.

Actins↗

[Impact of nutritional status, inflammation and cardiovascular disease on the mortality of 90 Chinese peritoneal dialysis patients].

OBJECTIVE: To investigate the impact of nutritional status, inflammation and cardiovascular disease on the mortality of 90 patients with continuous ambulatory peritoneal dialysis (CAPD). METHODS: A cross-sectional study was performed in 90 clinically stable CAPD patients. Patients' nutritional status (by SGA), chronic inflammation (by CRP), cardiovascular disease (CVD) were evaluated. All patients were followed for 24 months. RESULTS: Thirty-three of the 90 (36.67%) patients died during the follow-up, five patients transferred to hemodialysis and 3 patients received transplantation. The causes of death were CVD in 12, infection in 13 and other causes in 7. Seventeen patients who died were malnourished. Malnourished patients had significantly higher mortality than well nourished patients (P<0.05). Patients with high serum CRP had higher mortality (P<0.01). CVD patients had also significantly higher mortality (P<0.01). The patients with malnutrition-inflammation-CVD (MIA) syndrome had significantly lower survival rate as compared with those with one or two components of MIA (P<0.01). CONCLUSION: During 2-year follow up, 45 percent of 90 CAPD patients left the program. The most common causes of death were CVD and infection. Half of the patients who died were malnourished. Inflammation, malnutrition and CVD may have aggravated each other, and contributed to the poor outcome of this patient population.

Cardiovascular Diseases↗