In Alzheimers disease and other degenerative brain diseases, some types of nerve cells are more vulnerable to degeneration than others. Nerve cells known as the basal forebrain cholinergic neurons (BFCN) are especially vulnerable. These cells are known to be important for memory and attention, both of which decline in patients with Alzheimers disease. Calbindin is a protein found inside nerve cells that binds to calcium. It protects nerve cells from abnormal increases in calcium, which can cause degeneration of the cell. Changiz Geula, Ph.D., and colleagues have found that the levels of calbindin decline in BFCN cells during normal aging. They theorize that such declines may leave the cells vulnerable to degeneration caused by abnormally high calcium levels.. Dr. Geula and colleagues plan to study the role of calbinin in Alzheimers disease using two approaches. In the first approach, they will study the levels of calbindin in the BFCN cells that remain in individuals affected by Alzheimers ...

The CRELD1 gene currently has no well-established disease association; however, there is preliminary evidence supporting a correlation with autosomal dominant atrioventricular septal defects (PMID: 15857420, 21080147).

The adaptive evolution of BMP3 is consistent with the rapid evolution of the human skeletal system, although we do not have data that explains the mechanism for the selective advantage of the BMP3 variant. BMP3, is an antagonist of several osteogenic BMPs, and is a negative determinant of bone density [19]. Lacking the BMP3, mice have increased bone mass [19]. Potentially, the antagonistic activity of human BMP3 to osteogenic acting factors, and even the level of BMP signal, was adaptively changed via many amino acid substitutions during human evolution, which may diverge functionally from chimpanzee accounting for the skeletal differences [2], [30]. It still needs test by further functional experiment. The targets of selection operated on the BMP3 are different between European and East Asian evidenced by long-range haplotype test (Fig. 2). Within modern human populations, BMP3 may also diverge in the activity, expression level, accounting for the skeletal variation, such as body mass, because ...

The TGF-β superfamily is a large family of growth and differentiation factors that regulate a wide variety of cellular processes in many different cell types and biological contexts. Different family members regulate cell proliferation (both positively and negatively), migration, extracellular matrix elaboration, adhesion, survival and differentiation, in both developing embryos and adult organisms, ranging from worms to humans (Whitman, 1998; Massagué and Chen, 2000; Massagué et al., 2000). Aberrant signaling by TGF-β, the prototype of the family, has been implicated in a number of human diseases, including cancer, hereditary hemorrhagic telangiectasia, atherosclerosis, and fibrotic disease of the kidney, liver, and lung (Blobe et al., 2000). In addition, low levels of TGF-β signaling have been implicated in compromised wound healing, and inappropriately high levels of TGF-β signaling are associated with excessive scarring (Roberts and Sporn, 1993).. The mechanism of signaling by TGF-β ...

A fresh water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. HO8910 tumor cells, with inhibition percentages of Tasquinimod supplier 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon- (IFN-), increased the activity of murine […]. ...

TY - JOUR. T1 - Bone marrow-derived mesenchymal progenitor cells.. AU - Johnstone, Brian. AU - Yoo, Jung. PY - 2000. Y1 - 2000. UR - http://www.scopus.com/inward/record.url?scp=0033656936&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0033656936&partnerID=8YFLogxK. M3 - Article. C2 - 10948547. AN - SCOPUS:0033656936. VL - 137. SP - 313. EP - 315. JO - Methods in molecular biology (Clifton, N.J.). JF - Methods in molecular biology (Clifton, N.J.). SN - 1064-3745. ER - ...

In the present experiments, AP has been measured in Alk1+/− and in Alk1+/+ mice by both tail-cuff and radiotelemetry methods. We have used both methods to measure AP because movement restriction necessary for tail-cuff measurement can modify vasoactive responses, especially when the sympathetic nervous system is involved, and because acute (minutes) effects can be difficult to assess by the tail-cuff method. Besides, both acute and prolonged effects of the vasoactive substances have been recorded because the acute and the long-standing consequences of inhibiting or stimulating these regulatory pathways can be different (Emanueli et al., 1997). Measurements of AP by the tail-cuff method and by telemetry showed consistently higher SAP in Alk1+/− than in Alk1+/+ mice, with no significant differences in HR. It should be noted that arterial hypertension has not been reported as a common sign in individuals with hereditary hemorrhagic telangiectasia type 2, a fact that can be explained by the ...

Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is a key m

DICER1 RNAi inhibits osteogenic differentiation and proliferation of hADSCs. (a) DICER1 mRNA levels were determined in control-(si-cont) or DICER1 oligonucleoti

|p|Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins. BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is involved also in cardiac cell differentiation and epithelial to mesenchymal transition. BMP-2 and BMP-7 are osteogenic BMPs: they have been demonstrated to potently induce osteoblast differentiation in a variety of cell types.|/p||p|Bone morphogenetic protein 2 is shown to stimulate the production of bone and recombinant human protein (rhBMP-2) and is currently available for orthopaedic usage in the United States.|/p|

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MicroRNAs (miRNAs) are small noncoding RNAs that have important roles in gene regulation. We have previously reported that activin receptor-like kinase 7 (ALK7) and its ligand, Nodal, induce apoptosis in human epithelial ovarian cancer cells. In this study, we examined the regulation of ALK7 by miRNAs and demonstrate that miR-376c targets ALK7. Ectopic expression of miR-376c significantly increased cell proliferation and survival, enhanced spheroid formation and blocked Nodal-induced apoptosis. Interestingly, overexpression of miR-376c blocked cisplatin-induced cell death, whereas anti-miR-376c enhanced the effect of cisplatin. These effects of miR-376c were partially compensated by the overexpression of ALK7. Moreover, in serous carcinoma samples taken from ovarian cancer patients who responded well to chemotherapy, strong ALK7 staining and low miR-376c expression was detected. By contrast, ALK7 expression was weak and miR-376c levels were high in samples from patients who responded poorly to ...

In the present study, we investigated the effect of Notch signaling on BMP9-induced osteogenic differentiation in MSCs, and the possible mechanism underlying this process. Our findings suggested that Notch signaling can enhance the activity of BMP9 to induce osteogenic differentiation in MSCs, and this effect may be partly mediated by upregulation of ALK2.. BMP9, also called GDF-2, is one of the least studied BMPs (44). Numerous studies have indicated that BMP9 has pivotal biological functions in the areas of liver fibrosis, iron metabolism, cartilage formation and angiopoiesis, and recent studies have shown that BMP9 is the strongest inducer of osteogenic differentiation, which has been regarded as a potential factor in tissue engineering (45). The studies concerning BMP9-induced osteogenesis mechanism are conducive to its application in bone-related diseases. Previous research has indicated that fibroblast growth factor 2 (FGF2) inhibits BMP9-induced osteogenic differentiation by blocking ...

Previously reported that that FTO-knock out mice display postnatal growth retardation, which manifests as reduced body weight and bone mineral density (Guo et al., 2011); however, the molecular mechanism by which FTO stimulates osteogenic differentiation remains unknown. Here, we demonstrate for the first time that FTO stimulates osteogenic differentiation by inducing mild ER stress. The results of the current study illustrate one mechanism underlying the role of FTO in osteogenic differentiation. A relationship between FTO and AMPK has been previously reported (Pitman et al., 2013; Wu et al., 2017). One study demonstrated that AMPK decreases lipid accumulation in skeletal muscle cells by suppressing FTO expression (Wu et al., 2017). Another study revealed that knockdown of FTO reduces phosphorylation of AMPK in Alzheimers disease (Pitman et al., 2013). The current study demonstrated that activation of AMPK markedly increased expression of FTO and that a positive feedback loop existed between ...

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