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排序方式: 共有1405条查询结果,搜索用时 78 毫秒
1.
So Jeong Park Doo Ri Park Deepak Bhattarai Kyeong Lee Jaesang Kim Yun Soo Bae Soo Young Lee 《Molecules and cells》2014,37(8):628-635
2-(Trimethylammonium) ethyl (R)-3-methoxy-3-oxo-2-stearamidopropyl phosphate [(R)-TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient megakaryopoiesis. Here, we show that (R)-TEMOSPho blocks osteoclast maturation from progenitor cells of hematopoietic origin, as well as blocking the resorptive function of mature osteoclasts. The inhibitory effect of (R)-TEMOSPho on osteoclasts was due to a disruption of the actin cytoskeleton, resulting from impaired downstream signaling of c-Fms, a receptor for macrophage-colony stimulating factor linked to c-Cbl, phosphoinositol-3-kinase (PI3K), Vav3, and Rac1. In addition, (R)-TEMOSPho blocked inflammation-induced bone destruction by reducing the numbers of osteoclasts produced in mice. Thus, (R)-TEMOSPho may represent a promising new class of antiresorptive drugs for the treatment of bone loss associated with increased osteoclast maturation and activity. 相似文献
2.
Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones. 相似文献
3.
Intestinal iron absorption during suckling in mammals 总被引:1,自引:0,他引:1
The maintenance of appropriate iron levels is important for mammalian health, particularly during the rapid growth period
following birth. Too little iron can lead to irreversible damage to the developing central nervous system and too much iron
at this point can have adverse long term consequences, possibly due to excessive free radical production. In order to maintain
iron levels, intestinal iron absorption is very efficient in young mammals, such that almost all of the iron in breast milk
is utilized. However this high level of absorption is unable to be down regulated in response to excess iron as it can be
in adults, implying that different regulatory processes are involved during suckling. Various mechanisms have been proposed
to explain this high absorption, including enhanced expression of the proteins involved in iron absorption in adults (particularly
DMT1 and ferroportin), non-specific uptake via pinocytosis, and the uptake of lactoferrin bound iron by the lactoferrin receptor.
However, at present the precise mechanism is unclear. It is possible that all of these components contribute to the high intestinal
iron absorption seen during suckling, or a novel, as yet undescribed, mechanism could be involved. This review summarises
the evidence for and against each of the mechanisms described above and highlights how little is known about iron homeostasis
in this vital stage of development. 相似文献
4.
5.
Bornali Chakrabarti Hridoy R Bairagya Deepak Kr Mishra Pradip Kumar Chatterjee Bishnu P Mukhopadhyay 《Bioinformation》2013,9(3):126-133
Human matrix metalloproteinase-8 (hMMP-8) plays a important role in the progression of colorectal cancer, metastasis, multiple
sclerosis and rheumetoid arthritis. Extensive MD-simulation of the PDB and solvated structures of hMMP-8 has revealed the
presence of few conserved water molecules around the catalytic and structural zinc (ZnC and ZnS) ions. The coordination of two
conserved water molecules (W and WS) to ZnS and the H-bonding interaction of WS to S151 have indicated the plausible involvement
of that metal ion in the catalytic process. Beside this the coupling of ZnC and ZnS metal ions (ZnC – WH (W1)…..W2 ….H162 - ZnS)
through two conserved hydrophilic centers (occupied by water molecules) may also provide some rational on the recognition of
two zinc ions which were separated by ~13 Å in their X-ray structures. This unique recognition of both the Zn+2 ions in the enzyme
through conserved water molecules may be implemented/ exploited for the design of antiproteolytic agent using water mimic
drug design protocol. 相似文献
6.
Deepak Balasubramanian Lisa Schneper Hansi Kumari Kalai Mathee 《Nucleic acids research》2013,41(1):1-20
Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a ‘birds-eye’ view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies. 相似文献
7.
Singh Manisha Sharma Deepak Chauhan Rajni Goel Gunjan 《Probiotics and antimicrobial proteins》2019,11(3):850-856
Probiotics and Antimicrobial Proteins - The present study investigated skimmed milk and alginate-based encapsulation for protection of a probiotic strain, Lactobacillus gastricus BTM7 during... 相似文献
8.
9.
Birong Zhang James R. Kiefer Robert A. Blake Jae H. Chang Steven Hartman Ellen Rei Ingalla Tracy Kleinheinz Vidhi Mody Michelle Nannini Daniel F. Ortwine Yingqing Ran Amy Sambrone Deepak Sampath Maia Vinogradova Yu Zhong Jerome C. Nwachukwu Kendall W. Nettles Tommy Lai Jun Liang 《Bioorganic & medicinal chemistry letters》2019,29(7):905-911
Despite tremendous progress made in the understanding of the ERα signaling pathway and the approval of many therapeutic agents, ER+?breast cancer continues to be a leading cause of cancer death in women. We set out to discover compounds with a dual mechanism of action in which they not only compete with estradiol for binding with ERα, but also can induce the degradation of the ERα protein itself. We were attracted to the constrained chromenes containing a tetracyclic benzopyranobenzoxepine scaffold, which were reported as potent selective estrogen receptor modulators (SERMs). Incorporation of a fluoromethyl azetidine side chain yielded highly potent and efficacious selective estrogen receptor degraders (SERDs), such as 16aa and surprisingly, also its enantiomeric pair 16ab. Co-crystal structures of the enantiomeric pair 16aa and 16ab in complex with ERα revealed default (mimics the A-D rings of endogenous ligand estradiol) and core-flipped binding modes, rationalizing the equivalent potency observed for these enantiomers in the ERα degradation and MCF-7 anti-proliferation assays. 相似文献
10.
Mukherjee Somnath Sharma Deepak Upadhyaya Kailash C. 《Journal of plant biochemistry and biotechnology.》2022,31(4):915-924
Journal of Plant Biochemistry and Biotechnology - Plant genomes contain a sizeable fraction, ranging from 14 to 75% of retrotransposons (class I elements), predominantly comprising LTR (Long... 相似文献