Wnt/β-catenin Signaling Cascades in Cardiovascular Diseases

Cardiovascular diseases are a group of disorders of the heart and blood vessels,primarily including coronary heart disease,stroke,and other diseases.It is the world’s leading cause of death,and its incidence is increasing yearly.Hypertension is a major risk factor for cardiovascular disease.Wnt signaling comprises a series of highly conservative cascading events controlling fundamental biological processes.Wnt signaling pathways include the canonical Wnt pathway(or Wnt/β-catenin pathway),the non canonical planar cell-polarity pathway,and the non-canonical calcium-dependent pathways.Abnormal Wnt signaling promotes cell proliferation and differentiation,cardiac malformations,various malignancies,so drugs targeting Wnt signaling play a great therapeutic potential.Wnt/β-catenin pathway is involved in the occurrence and development of cardiovascular diseases such as atherosclerosis and stroke by regulating cell proliferation,migration,apoptosis,blood-brain barrier permeability,inflammation,oxidative stress,and immune response.Based on the latest research progress,this review summarizes the role of Wnt/β-catenin signaling in cardiovascular diseases,in order to provide new ideas for the prevention and treatment of cardiovascular diseases.

Argonaute protein as a linker to command center of physiological processes

MicroRNAs （miRNAs） post-transcriptionally regulate gene expression by binding to target mRNAs with perfect or imperfect complementarity, recruiting an Argonaute （AGO） protein complex that usually results in degradation or translational repression of the target mRNA. AGO proteins function as the Slicer enzyme in miRNA and small interfering RNA （siRNA） pathways involved in human physiological and pathophysiological processes, such as antiviral responses and disease formation. Although the past decade has witnessed rapid advancement in studies of AGO protein functions, to further elucidate the molecular mechanism of AGO proteins in cellular function and biochemical process is really a challenging area for researchers. In order to understand the molecular causes underlying the pathological processes, we mainly focus on five fundamental problems of AGO proteins, including evolution, functional domain, subcellular location, post-translational modification and protein-protein interactions. Our discussion highlight their roles in early diagnosis, disease prevention, drug target identification, drug response, etc.

An Experimental Study of Pathogenesis of Steroid-induced Avascular Necrosis of Femoral Head

Objective: To explore the pathogenesis of avascular necrosis of femoral head(ANFH) and search an effective method for clinical practice. Methods: Twenty-four Japanese rabbitswere divided into 2 groups of models and controls. ANFH models were produced byintramuscular-injection of large dosage of steroid to rabbits for 8 weeks. From the 4th, 8th and12th week after production of models, 2 rabbits of each group were sacrificed to observe thestructure of femoral head through light microscope and scanning electron microscope. The contents ofNitric Oxide (NO), tissue-type plasminogen activator (t-PA) and -plasminogen activator inhibitor(PAI) in plasma of the 4 rabbits in each group were estimated at the same time. Results: Comparedwith control group, the rabbits of model group exhibited many differences: such as osteoporosis offemoral head, the presence of more bone lacuna and fat cell through light microscope observing; thebroken and sunk bone trabecula, the loosen and broken collagen fibers on the surface of bone matrixthrough scanning electron microscope observing. Compared with control group, the Concentration ofNO and t-PA in plasma of the model rabbits decreased obviously, but the Concentration of the PAIincreased obviously. Conclusion: The steroid-induced ANFH might be related to the lower level of NOand the descent of fibrinolytic activity.

Experimental study of changes of TNF-α in rabbits with steroid-induced avascular necrosis of femoral head

Objective: To explore the effect of tumor necrosis factor-α(TNF-α)on the occurrence of steroid-induced avascular necrosis of femoral head(SANFH). Methods: Twenty-four rabbits were firstly divided into void group (n=12) and model group (n=12) at random. Prednisone Acetate was injected to the model group(0.32 mg·kg^(-1)·d^(-1)). In the 6 th and 8 th week, two rabbits of the two groups were killed respectively to observe whether the model was successful. The level of TNF-α in serum of the residual rabbits of the two groups was examined in Radioimmunoassay method. Results: The level of TNF-α in model group is significantly higher than that in void group(P<0.001) under the premise of the model of SANFH success by histological observation. Conclusion: The rise of level of TNF-α may be one of the most important factors in the occurrence of SANFH.

SAFETY MARGIN IN ANUS-SAVING RESECTION FOR LOW RECTAL CANCER

The length and method of measurement of the safety-margin below the rectal cancer, being of the utmost importance for its prognosis, is still under debate.The following study was designed and done for its solution.Light microscopic examination was done on 83 resected rectal cancer specimens to assess the extent of intramural invasion towards the anus.By use of a ruler,the distance between the lower tumour margin and the resection line or the dentate line was measured when the specimen was:l. freshly resected,2.after fixing in 10% formalin, and 3.after being mounted in sections. The measurements were compared. By the same method,the distance between the lower tumor margin and the intended resectyion line was measured immediately before resection.It was compared with the measurement immediately after the resection.In 83 rectal cancer specimens, the extent of intramural infiltration toward the anus was:≤0.5 cm in 75 cases (90.4%).≥l cm in 2 cases which showed highly malignant carcinomas.These 2 cases, however,should not have been indicated for anus-saving resection.In 46 fresh specimens,the tumor-resection line distances gave an average of 2.7 cm.After fixing in 10% formalin, they became shortened by 0.7 cm. And, mouting in sections further shortened them by another 0.5 cm,giving a total shortening of l.2 cm.The tumor-resection line distance in 7 of the 11 fresh specimens resected by the Dixon's operation was shortened,though never more than o.5 cm immediately the operation.In performin ganus-saving resection for the low rectal cancer, after full isolation the rectum and stretching it slightly,≥3 cm of the rectum distal to the lower tumor margin should be resected.A safety margin of more than 2.5 cm is necessary in the fresh specimen.If formalin fixed specimen is measured, the safety margin should be ≥2 cm.

Long non-coding RNA-guided regulation in organisms

It is clear that RNA is more than just a messenger between gene and protein.The mammalian genome is pervasively transcribed,giving rise to tens of thousands of non-coding transcripts.Whether all of these transcripts are functional remains to be elucidated,but it is evident that there are many functional long non-coding RNAs(lncRNAs).Recent studies have set out to decode the regulatory role and functional diversity of lncRNAs.Here we organize these studies to highlight the significant involvements of lncRNAs in regulation of gene expression and human physiological and pathological processes,which are achieved by their interaction with DNA,RNA or protein.