-
Chaofeng Yang,
Weiqin Lu,
Tao Lin,
Pan You,
Min Ye,
Yanqing Huang,
Xianhan Jiang,
Cong Wang, Fen Wang,
Mong-Hong Lee,
Sai-Ching J Yeung,
Randy L Johnson,
Chongjuan Wei,
Robert Y Tsai,
Marsha L Frazier,
Wallace L McKeehan,
Yongde Luo
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: FGF21 is a promising intervention therapy for metabolic diseases as fatty liver, obesity and diabetes. Recent results suggest that FGF21 is highly expressed in hepatocytes under metabolic stress caused by starvation, hepatosteatosis, obesity and diabetes. Hepatic FGF21 elicits metabolic benefits by targeting adipocytes of the peripheral adipose tissue through the transmembrane FGFR1-KLB complex. Ablation of adipose FGFR1 resulted in increased hepatosteatosis under starvation conditions and abrogation of the anti-obesogenic action of FGF21. These results indicate that FGF21 may be a stress responsive hepatokine that targets adipocytes and adipose tissue for alleviating the damaging effects of stress on the liver. However, it is unclear whether hepatic induction of FGF21 is limited to only metabolic stress, or to a more general hepatic stress resulting from liver pathogenesis and injury. METHODS: In this survey-based study, we examine the nature of hepatic FGF21 activation in liver tissues and tissue sections from several mouse liver disease models and human patients, by quantitative PCR, immunohistochemistry, protein chemistry, and reporter and CHIP assays. The liver diseases include genetic and chemical-induced HCC, liver injury and regeneration, cirrhosis, and other types of liver diseases. RESULTS: We found that mouse FGF21 is induced in response to chemical (DEN treatment) and genetic-induced hepatocarcinogenesis (disruptions in LKB1, p53, MST1/2, SAV1 and PTEN). It is also induced in response to loss of liver mass due to partial hepatectomy followed by regeneration. The induction of FGF21 expression is potentially under the control of stress responsive transcription factors p53 and STAT3. Serum FGF21 levels correlate with FGF21 expression in hepatocytes. In patients with hepatitis, fatty degeneration, cirrhosis and liver tumors, FGF21 levels in hepatocytes or phenotypically normal hepatocytes are invariably elevated compared to normal health subjects. CONCLUSION: FGF21 is an inducible hepatokine and could be a biomarker for normal hepatocyte function. Activation of its expression is a response of functional hepatocytes to a broad spectrum of pathological changes that impose both cellular and metabolic stress on the liver. Taken together with our recent data, we suggest that hepatic FGF21 is a general stress responsive factor that targets adipose tissue for normalizing local and systemic metabolic parameters while alleviating the overload and damaging effects imposed by the pathogenic stress on the liver. This study therefore provides a rationale for clinical biomarker studies in humans.
BMC Gastroenterology 04/2013; 13(1):67. · 2.42 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The fibroblast growth factor receptor FGFR1 is ectopically expressed in prostate carcinoma cells, but its functional contributions are undefined. In this study, we report the evalulation of a tissue-specific conditional deletion mutant generated in an ARR2PBi(Pbsn)-Cre/TRAMP/fgfr1loxP/loxP transgenic mouse model of prostate cancer. Mice lacking fgfr1 in prostate cells developed smaller tumors that also included distinct cancer foci still expressing fgfr1 indicating focal escape from gene excision. Tumors with confirmed fgfr1 deletion exhibited increased foci of early, well-differentiated cancer and phyllodes-type tumors, and tumors that escaped fgfr1 deletion primarily exhibited a poorly differentiated phenotype. Consistent with these phenotypes, mice carrying the fgfr1 null allele survived significantly longer than those without fgfr1 deletion. Most interestingly, all metastases were primarily negative for the fgfr1 null allele, exhibited high FgfR1 expression and a neuroendocrine phenotype regardless of fgfr1 status in the primary tumors. Together, these results suggest a critical and permissive role of ectopic FGFR1 signaling in prostate tumorigenesis and particularly in mechanisms of metastasis.
Cancer Research 04/2013; · 7.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AgOTf can catalyze an addition-cyclization tandem between alkyne-azomethine and a nucleophile such as ketone, nitroalkane, water, and terminal alkyne to give a polycyclic amide via six-exo-trig selectivity.
Organic Letters 02/2013; · 5.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Jun is a highly conserved member of the multimeric activator protein 1 transcription factor complex and plays an important role in human cancer where it is known to be critical for proliferation, cell cycle regulation, differentiation, and cell death. All of these biological functions are also crucial for embryonic development. Although all Jun null mouse embryos die at mid-gestation with persistent truncus arteriosus, a severe cardiac outflow tract defect also seen in human congenital heart disease, the developmental mechanisms are poorly understood. Here we show that murine Jun is expressed in a restricted pattern in several cell populations important for cardiovascular development, including the second heart field, pharyngeal endoderm, outflow tract and atrioventricular endocardial cushions and post-migratory neural crest derivatives. Several genes, including Isl1, molecularly mark the second heart field. Isl1 lineages include myocardium, smooth muscle, neural crest, endocardium, and endothelium. We demonstrate that conditional knockout mouse embryos lacking Jun in Isl1-expressing progenitors display ventricular septal defects, double outlet right ventricle, semilunar valve hyperplasia and aortic arch artery patterning defects. In contrast, we show that conditional deletion of Jun in Tie2-expressing endothelial and endocardial precursors does not result in aortic arch artery patterning defects or embryonic death, but does result in ventricular septal defects and a low incidence of semilunar valve defects, atrioventricular valve defects and double outlet right ventricle. Our results demonstrate that Jun is required in Isl1-expressing progenitors and, to a lesser extent, in endothelial cells and endothelial-derived endocardium for cardiovascular development but is dispensable in both cell types for embryonic survival. These data provide a cellular framework for understanding the role of Jun in the pathogenesis of congenital heart disease.
PLoS ONE 01/2013; 8(2):e57032. · 4.09 Impact Factor
-
Zhongcheng Shi,
Zhenyu Cai,
Jingcui Yu,
Tingting Zhang,
Shu Zhao,
Emanuel Smeds,
Qingyuan Zhang, Fen Wang,
Changhong Zhao,
Songbin Fu,
Sankar Ghosh,
Dekai Zhang
[show abstract]
[hide abstract]
ABSTRACT: Toll-like receptors (TLRs) are key molecular sensors used by the mammalian innate immune system to detect microorganisms. Although TLR functions in colonic immune homeostasis and tolerance to commensal bacteria have been intensively researched, the precise roles of different TLRs in response to pathogen infection in the gut remain elusive. Peyer patches are the major entrance of Salmonella infection and antigen transportation in intestine. Here, we report that, in contrast to TLR5 as a carrier of Salmonella, TLR11 works as a blocker of Salmonella to prevent highly invasive Salmonella from penetrating into the murine Peyer patches and spreading systemically. TLR11 plays an important role in mediating TNF-alpha induction and systemic inflammation in response to Salmonella infection. Remarkably, mice lacking TLR11 are induced apparent hemorrhage at Peyer patches by highly invasive Salmonella, a phenotype resembling human Salmonella infection. Therefore, our results indicate a potentially important role for TLR11 in preventing murine intestinal infection and modulating antigen transportation in the gut and imply an important role for various TLRs in cooperation to tightly control of pathogens penetrating into Peyer patches. TLR11 knockout mouse can serve as a good animal model to study Salmonella infection.
Journal of Biological Chemistry 11/2012; · 4.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: Endocrine FGF19 and FGF21 exert their effects on metabolic homeostasis through fibroblast growth factor receptor (FGFR) and co-factor betaKlotho (KLB). Ileal FGF19 regulates bile acid metabolism through specifically FGFR4-KLB in hepatocytes where FGFR1 is not significant. Both FGF19 and FGF21 activate FGFR1-KLB whose function predominates in adipocytes. Recent studies using administration of FGF19 and FGF21 and genetic ablation of KLB or adipocyte FGFR1 indicate that FGFR1-KLB mediates the response of adipocytes to both FGF21 and FGF19. Here we show that adipose FGFR1 regulates lipid metabolism through direct effect on adipose tissue and indirect effects on liver under starvation conditions that cause hepatic stress. METHODS: We employed adipocyte-specific ablations of FGFR1 and FGFR2 genes in mice, and analyzed metabolic consequences in adipose tissue, liver and systemic parameters under normal, fasting and starvation conditions. RESULTS: Under normal conditions, the ablation of adipose FGFR1 had little effect on adipocytes, but caused shifts in expression of hepatic genes involved in lipid metabolism. Starvation conditions precipitated a concurrent elevation of serum triglycerides and non-esterified fatty acids, and increased hepatic steatosis and adipose lipolysis in the FGFR1-deficient mice. Little effect on glucose or ketone bodies due to the FGFR1 deficiency was observed. CONCLUSIONS: Our results suggest an adipocyte-hepatocyte communication network mediated by adipocyte FGFR1 that concurrently dampens hepatic lipogenesis and adipocyte lipolysis. We propose that this serves overall to mete out and extend lipid reserves for neural fuels (glucose and ketone bodies), while at the same time governing extent of hepatosteatosis during metabolic extremes and other conditions causing hepatic stress.
Nutrition & Metabolism 10/2012; 9(1):94. · 2.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Olefinic CH activation of N-allyl sulfonamides in the presence of [{RhCp*Cl(2) }(2) ] (Cp*=Me(5) C(5) ) enabled their oxidative coupling with alkynes to generate 1,2-dihydropyridines, pyridines, and cyclopentenones (see scheme; Ts=p-toluenesulfonyl). The type of highly substituted product formed was controlled by the substitution of the allyl group and the reaction conditions.
Angewandte Chemie International Edition 10/2012; · 13.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Put it on a ring: A rhodium(III) complex can catalyze the oxidative coupling of azomethine imines with olefins, leading to the synthesis of 1,2-dihydrophthalazines, olefinated aldehydes, or fused pyridines, depending on the conditions used.
Angewandte Chemie International Edition 10/2012; · 13.45 Impact Factor
-
Yi Xing,
Cuibai Wei,
Changbiao Chu,
Aihong Zhou,
Fang Li,
Liyong Wu,
Haiqing Song,
Xiumei Zuo, Fen Wang,
Wei Qin,
Dan Li,
Yi Tang,
Xiang-Fei Jia,
Jianping Jia
[show abstract]
[hide abstract]
ABSTRACT: Studies on gender differences in the clinical manifestations of vascular dementia (VaD) are still lacking. In the present study, gender comparisons of cognitive and neuropsychiatric profiles were conducted separately for mild and moderate-to-severe VaD in a total of 467 patients with VaD. There were no significant gender differences in cognitive manifestations, except that females performed better on immediate verbal recall than males in mild stage. Women were more likely to exhibit delusions (15.5% vs 7.4%), hallucinations (9.5% vs 3.4%), and depression (43.1% vs 27.3%) in mild stage. The predominance of male patients was observed in apathy at moderate-to-severe stage (50.5% vs 34.8%). To conclude, gender differences existed in neuropsychiatric symptoms of VaD and were especially pronounced in mild stage. Delusions, hallucinations, and depression were more prevalent in females in mild VaD, with the male predominance only in apathy in the later stage.
American Journal of Alzheimer s Disease and Other Dementias 09/2012; 27(6):433-8. · 1.45 Impact Factor
-
Daniel J Klionsky,
Fabio C Abdalla,
Hagai Abeliovich,
Robert T Abraham,
Abraham Acevedo-Arozena,
Khosrow Adeli,
Lotta Agholme,
Maria Agnello,
Patrizia Agostinis,
Julio A Aguirre-Ghiso, [......],
Changlian Zhu,
Wei-Guo Zhu,
Xiao-Feng Zhu,
Xiongwei Zhu,
Yuangang Zhu,
Teresa Zoladek,
Wei-Xing Zong,
Antonio Zorzano,
Jürgen Zschocke,
Brian Zuckerbraun
[show abstract]
[hide abstract]
ABSTRACT: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
Autophagy 04/2012; 8(4):445-544. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The fibroblast growth factor (FGF) signaling axis plays important roles in heart development. Yet, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Using genetically engineered mouse and in vitro cultured embryoid body (EB) models, we demonstrate that FGF signaling suppresses premature differentiation of heart progenitor cells, as well as autophagy in outflow tract (OFT) myocardiac cells. The FGF also promotes mesoderm differentiation in embryonic stem cells (ESCs) but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, inhibition of FGF signaling increases myocardial differentiation and autophagy in both ex vivo cultured embryos and EBs, whereas activation of autophagy promotes myocardial differentiation. Thus, a link between FGF signals preventing premature differentiation of heart progenitor cells and suppression of autophagy has been established. These findings provide the first evidence that autophagy plays a role in heart progenitor differentiation, and suggest a new venue to regulate stem/progenitor cell differentiation.
Autophagy 04/2012; 8(4):690-1. · 7.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although functionally similar proteins across species have been widely studied, functionally similar proteins within species showing low sequence similarity have not been examined in detail. Identification of these proteins is of significant importance for understanding biological functions, evolution of protein families, progression of co-evolution, and convergent evolution and others which cannot be obtained by detection of functionally similar proteins across species. Here, we explored a method of detecting functionally similar proteins within species based on graph theory. After denoting protein-protein interaction networks using graphs, we split the graphs into subgraphs using the 1-hop method. Proteins with functional similarities in a species were detected using a method of modified shortest path to compare these subgraphs and to find the eligible optimal results. Using seven protein-protein interaction networks and this method, some functionally similar proteins with low sequence similarity that cannot detected by sequence alignment were identified. By analyzing the results, we found that, sometimes, it is difficult to separate homologous from convergent evolution. Evaluation of the performance of our method by gene ontology term overlap showed that the precision of our method was excellent.
Proteins Structure Function and Bioinformatics 03/2012; 80(7):1736-43. · 3.39 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Rhodium(III)-catalyzed direct functionalization of C-H bonds under oxidative conditions leading to C-C, C-N, and C-O bond formation is reviewed. Various arene substrates bearing nitrogen and oxygen directing groups are covered in their coupling with unsaturated partners such as alkenes and alkynes. The facile construction of C-E (E = C, N, S, or O) bonds makes Rh(III) catalysis an attractive step-economic approach to value-added molecules from readily available starting materials. Comparisons and contrasts between rhodium(III) and palladium(II)-catalyzed oxidative coupling are made. The remarkable diversity of structures accessible is demonstrated with various recent examples, with a proposed mechanism for each transformation being briefly summarized (critical review, 138 references).
Chemical Society Reviews 02/2012; 41(9):3651-78. · 28.76 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Tetrasubstituted pyrroles have been synthesized via the cross-dehydrogenative coupling between enamino esters and acetone. Silver carbonate proved to be an effective oxidant, and no transition metal catalyst is necessary.
Organic Letters 02/2012; 14(6):1412-5. · 5.86 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Microtubule-associated protein 1 small form (MAP1S; originally named C19ORF5) was identified as serving as linkers to connect mitochondria with microtubules for trafficking, and to bridge the autophagy machinery with microtubules and mitochondria to affect autophagosomal biogenesis and degradation. We found that MAP1S levels become elevated immediately in response to diethylnitrosamine-induced or genome instability-driven metabolic stress in a murine model of hepatocarcinoma. Elevation of MAP1S enhances autophagy to remove p62-associated aggresomes and dysfunctional organelles that trigger DNA double-strand (DSB) breaks and genome instability. The early accumulation of an unstable genome prior to signs of tumorigenesis suggested that genome instability causes tumorigenesis. After tumorigenesis, tumor development then triggers the activation of autophagy to reduce genome instability in tumor foci. We concluded that an increase in MAP1S levels triggers autophagy in order to suppress genome instability so that both the incidence of diethylnitrosamine-induced hepatocarcinogenesis and malignant progression are suppressed. Thus, a link between MAP1S-enhanced autophagy and suppression of genomic instability and tumorigenesis has been established.
Autophagy 02/2012; 8(2):278-80. · 7.45 Impact Factor
-
Xiangsheng Yang,
Qi Li,
Xi Lin,
Yanlin Ma,
Xiaojing Yue,
Zhenyin Tao, Fen Wang,
Wallace L Mckeehan,
Lei Wei,
Robert J Schwartz,
Jiang Chang
[show abstract]
[hide abstract]
ABSTRACT: We have previously found that in failing human hearts, Rho-associated coiled-coil protein kinase 1 (ROCK1) is processed by caspase-3 into an active isoform, ROCKΔ1. The purpose of the current investigation was to elucidate the pathological consequences of truncated ROCK1 accumulation in the heart, the associated molecular mechanism of ROCKΔ1-mediated cardiac phenotype, and the molecular signaling between Rho kinase activation in cardiomyocytes and extracellular matrix response. We generated transgenic mice expressing ROCKΔ1 in cardiomyocytes to mimic the situation observed in human heart disease, whereas an additional kinase-deficient mouse was generated as a control. The ROCKΔ1 transgenic mice developed fibrotic cardiomyopathy with diastolic dysfunction. Transgenic hearts displayed activated TGFβ1 and NF-κB signaling and a release of a subset of cytokines and were susceptible to angiotensin II stress. Treatment with a Rho kinase inhibitor attenuated the fibrotic phenotype. Cardiac fibroblasts differentiated into myofibroblasts when cocultured with transgenic cardiomyocytes but not with wild-type cardiomyocytes. Inhibitors of Rho kinase as well as TGFβR1 and NF-κB decreased these effects. The serum response factor-dependent TGFβ1 regulation was shown to be responsible for the Rho kinase-mediated activation of TGFβ1 signaling. We conclude that ROCKΔ1 is a novel fibrotic factor. Activation of TGFβ1 and NF-κB signaling contributes to the Rho kinase-mediated pathological fibrosis.
The FASEB Journal 01/2012; 26(5):2105-16. · 5.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Studying the large-scale protein-protein interaction (PPI) network is important in understanding biological processes. The current research presents the first PPI map of swine, which aims to give new insights into understanding their biological processes.
We used three methods, Interolog-based prediction of porcine PPI network, domain-motif interactions from structural topology-based prediction of porcine PPI network and motif-motif interactions from structural topology-based prediction of porcine PPI network, to predict porcine protein interactions among 25,767 porcine proteins. We predicted 20,213, 331,484, and 218,705 porcine PPIs respectively, merged the three results into 567,441 PPIs, constructed four PPI networks, and analyzed the topological properties of the porcine PPI networks. Our predictions were validated with Pfam domain annotations and GO annotations. Averages of 70, 10,495, and 863 interactions were related to the Pfam domain-interacting pairs in iPfam database. For comparison, randomized networks were generated, and averages of only 4.24, 66.79, and 44.26 interactions were associated with Pfam domain-interacting pairs in iPfam database. In GO annotations, we found 52.68%, 75.54%, 27.20% of the predicted PPIs sharing GO terms respectively. However, the number of PPI pairs sharing GO terms in the 10,000 randomized networks reached 52.68%, 75.54%, 27.20% is 0. Finally, we determined the accuracy and precision of the methods. The methods yielded accuracies of 0.92, 0.53, and 0.50 at precisions of about 0.93, 0.74, and 0.75, respectively.
The results reveal that the predicted PPI networks are considerably reliable. The present research is an important pioneering work on protein function research. The porcine PPI data set, the confidence score of each interaction and a list of related data are available at (http://pppid.biositemap.com/).
Proteome Science 01/2012; 10(1):2. · 2.33 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent studies suggest that betaKlotho (KLB) and endocrine FGF19 and FGF21 redirect FGFR signaling to regulation of metabolic homeostasis and suppression of obesity and diabetes. However, the identity of the predominant metabolic tissue in which a major FGFR-KLB resides that critically mediates the differential actions and metabolism effects of FGF19 and FGF21 remain unclear.
We determined the receptor and tissue specificity of FGF21 in comparison to FGF19 by using direct, sensitive and quantitative binding kinetics, and downstream signal transduction and expression of early response gene upon administration of FGF19 and FGF21 in mice. We found that FGF21 binds FGFR1 with much higher affinity than FGFR4 in presence of KLB; while FGF19 binds both FGFR1 and FGFR4 in presence of KLB with comparable affinity. The interaction of FGF21 with FGFR4-KLB is very weak even at high concentration and could be negligible at physiological concentration. Both FGF19 and FGF21 but not FGF1 exhibit binding affinity to KLB. The binding of FGF1 is dependent on where FGFRs are present. Both FGF19 and FGF21 are unable to displace the FGF1 binding, and conversely FGF1 cannot displace FGF19 and FGF21 binding. These results indicate that KLB is an indispensable mediator for the binding of FGF19 and FGF21 to FGFRs that is not required for FGF1. Although FGF19 can predominantly activate the responses of the liver and to a less extent the adipose tissue, FGF21 can do so significantly only in the adipose tissue and adipocytes. Among several metabolic and endocrine tissues, the response of adipose tissue to FGF21 is predominant, and can be blunted by the ablation of KLB or FGFR1.
Our results indicate that unlike FGF19, FGF21 is unable to bind FGFR4-KLB complex with affinity comparable to FGFR1-KLB, and therefore, at physiological concentration less likely to directly and significantly target the liver where FGFR4-KLB predominantly resides. However, both FGF21 and FGF19 have the potential to activate responses of primarily the adipose tissue where FGFR1-KLB resides.
PLoS ONE 01/2012; 7(3):e33870. · 4.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The innovated needling methods of "warm reinforcing technique" and "cold reducing technique" by professor ZHENG Kui-shan was analyzed. The discussion on these methods was done in comparison with the techniques of "setting the mountain on fire" and "penetrating the heaven coolness". The innovations and the clinical application advantages were explored. ZHENG's "warm reinforcing technique" and "cold reducing technique" were based on the techniques of setting the mountain on fire" and "penetrating the heaven coolness". These techniques were the complex of the simple techniques of reinforcing and reducing, such as rotating, lifting and thrusting, assistant reinforcing and reducing, as well as reinforcing and reducing by keeping the acupoint open or not. Of those different techniques, reinforcing and reducing by rotating needling and the assistant method are recommended by prof. ZHENG and they are the characteristics of ZHENG's needling technique. Compared with the techniques of "setting the mountain on fire" and "penetrating the heaven coolness", "warm reinforcing technique" and "cold reducing technique" are simple in operation and widely applied in clinical practice. Moreover, these techniques have the same efficacy as the techniques of "setting the mountain on fire" and "penetrating the heaven coolness".
Zhongguo zhen jiu = Chinese acupuncture & moxibustion 01/2012; 32(1):35-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Although the fibroblast growth factor (FGF) signaling axis plays important roles in heart development, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood.
To investigate the mechanism by which FGF signaling regulates cardiac progenitor cell differentiation.
Using mice with tissue-specific ablation of FGF receptors and FGF receptor substrate 2α (Frs2α) in heart progenitor cells, we demonstrate that disruption of FGF signaling leads to premature differentiation of cardiac progenitor cells in mice. Using embryoid body cultures of mouse embryonic stem cells, we reveal that FGF signaling promotes mesoderm differentiation in embryonic stem cells but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, we also report that inhibiting FRS2α-mediated signals increases autophagy and that activating autophagy promotes myocardial differentiation and vice versa.
The results indicate that the FGF/FRS2α-mediated signals prevent premature differentiation of heart progenitor cells through suppressing autophagy. The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation.
Circulation Research 12/2011; 110(4):e29-39. · 9.49 Impact Factor
