排序方式: 共有41条查询结果,搜索用时 15 毫秒
11.
Zeyuan Song Tao Wu Jinpeng Sun Haoran Wang Feng Hua Yap San Min Nicolas Rupesh KC Kun Chen Zhen Jin Jun Liu Mingshun Zhang 《Journal of cellular and molecular medicine》2021,25(7):3272-3283
Excessive post-epidural fibrosis is a common cause of recurrent back pain after spinal surgery. Though various treatment methods have been conducted, the safe and effective drug for alleviating post-epidural fibrosis remains largely unknown. Metformin, a medicine used in the treatment of type 2 diabetes, has been noted to relieve fibrosis in various organs. In the present study, we aimed to explore the roles and mechanisms of metformin in scar formation in a mouse model of laminectomy. Post-epidural fibrosis developed in a mouse model of laminectomy by spinous process and the T12-L2 vertebral plate with a rongeur. With the administration of metformin, post-epidural fibrosis was reduced, accompanied with decreased collagen and fibronectin in the scar tissues. Mechanistically, metformin decreased fibronectin and collagen deposition in fibroblast cells, and this effect was dependent on the HMGB1/TLR4 and TGF-β1/Smad3 signalling pathways. In addition, metformin influenced the metabolomics of the fibroblast cells. Taken together, our study suggests that metformin may be a potential option to mitigate epidural fibrosis after laminectomy. 相似文献
12.
Andrew MF Liu Rico KH Lo Emily X Guo Maurice KC Ho Richard D Ye Yung H Wong 《BMC structural biology》2011,11(1):17
Background
G protein-coupled receptors constitute the largest family of cell surface receptors in the mammalian genome. As the core of the G protein signal transduction machinery, the Gα subunits are required to interact with multiple partners. The GTP-bound active state of many Gα subunits can bind a multitude of effectors and regulatory proteins. Yet it remains unclear if the different proteins utilize distinct or common structural motifs on the Gα subunit for binding. Using Gα16 as a model, we asked if its recently discovered adaptor protein tetratricopeptide repeat 1 (TPR1) binds to the same region as its canonical effector, phospholipase Cβ (PLCβ). 相似文献13.
Jae‐Sung Kim Michael B. Ellman Dongyao Yan Howard S. An Ranjan KC Xin Li Di Chen Guozhi Xiao Gabriella Cs‐Szabo David W. Hoskin Doug D. Buechter Andre J. Van Wijnen Hee‐Jeong Im 《Journal of cellular physiology》2013,228(9):1884-1896
The catabolic cytokine interleukin‐1 (IL‐1) and endotoxin lipopolysaccharide (LPS) are well‐known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL‐1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti‐catabolic and anti‐inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL‐1 and LPS‐mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL‐1 and LPS‐mediated proteoglycan (PG) depletion, matrix‐degrading enzyme production, and enzyme activity in long‐term (alginate beads) and short‐term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL‐1 and LPS‐mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage‐degrading enzymes, including MMP‐1, MMP‐3, MMP‐13, ADAMTS‐4, and ADAMTS‐5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor‐induced stimulation of oxidative and inflammatory factors such as iNOS, IL‐6, and toll‐like receptor‐2 (TLR‐2) and TLR‐4. Finally, the ability of LfcinB to antagonize IL‐1 and LPS‐mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. J. Cell. Physiol. 228: 1884–1896, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
14.
Jessica L. Thornton Vaskar Nepal KC Leslie D. Frankland Craig R. Jansen Jana Hirst Robert E. Colombo 《Zeitschrift fur angewandte Ichthyologie》2019,35(1):360-369
Shovelnose sturgeon (Scaphirhynchus platorynchus, Rafinesque, 1820) in the Wabash River, Illinois/Indiana, USA, provide an important recreational sport and commercial caviar fishery. In fact, it is one of the last commercially viable populations for sturgeon roe harvest. Due to increased demand in the caviar trade and endangered species legislation that protect shovelnose sturgeon in only a portion of their range, efforts of the roe harvest market may continue to divert toward unprotected populations like the shovelnose sturgeon in the Wabash River. Previous studies have shown that increased harvest pressure in this species can affect the age‐at‐maturation and result in recruitment overfishing. Therefore, it is important to closely and continuously monitor commercially exploited populations. Over the past decade (2007–2016), 13,170 shovelnose sturgeon were sampled with boat electroshocking, hoop nets, drift nets, trotlines, and benthic electrified trawls. Captured fish ranged from 61 to 910 mm fork length (FL; mean = 668 mm), with very few fish less than 550 mm FL. Although fish were found to be in a healthy condition (mean relative weight = 87), there was a decrease in the mean condition over time. In addition, we saw declines in mean FL, weight of roe‐per‐fish, and size‐at‐maturity for female fish directly impacted by harvest. The decline of these population parameters, coupled with an increase in total annual mortality and a truncated age frequency distribution, suggest that harvest is negatively impacting the demographics and recruitment of shovelnose sturgeon in the Wabash River. Considering the downward trajectory of population dynamics and high estimates of mortality, their resiliency to continued harvest and environmental changes will be limited. 相似文献
15.
Frankenswine,or bringing home the bacon: How close are we to clinical trials in xenotransplantation?
David KC Cooper 《Organogenesis》2008,4(1):1-10
Xenotransplantation—specifically from pig into human—could resolve the critical shortage of organs, tissues and cells for clinical transplantation. Genetic engineering techniques in pigs are relatively well-developed and to date have largely been aimed at producing pigs that either (1) express high levels of one or more human complement-regulatory protein(s), such as decay-accelerating factor or membrane cofactor protein, or (2) have deletion of the gene responsible for the expression of the oligosaccharide, Galα1,3Gal (Gal), the major target for human anti-pig antibodies, or (3) have both manipulations. Currently the transplantation of pig organs in adequately-immunosuppressed baboons results in graft function for periods of 2–6 months (auxiliary hearts) and 2–3 months (life-supporting kidneys). Pig islets have maintained normoglycemia in diabetic monkeys for >6 months. The remaining immunologic barriers to successful xenotransplantation are discussed, and brief reviews made of (1) the potential risk of the transmission of an infectious microorganism from pig to patient and possibly to the public at large, (2) the potential physiologic incompatibilities between a pig organ and its human counterpart, (3) the major ethical considerations of clinical xenotransplantation, and (4) the possible alternatives that compete with xenotransplantation in the field of organ or cell replacement, such as mechanical devices, tissue engineering, stem cell biology and organogenesis. Finally, the proximity of clinical trials is discussed. Islet xenotransplantation is already at the stage where clinical trials are actively being considered, but the transplantation of pig organs will probably require further genetic modifications to be made to the organ-source pigs to protect their tissues from the coagulation/anticoagulation dysfunction that plays a significant role in pig graft failure after transplantation in primates.Key words: islets, pancreatic, genetic engineering, organogenesis, pig, xenotransplantation 相似文献
16.
17.
18.
Background
Environmental pH stress constitutes a limiting factor for S. meliloti survival and development. The response to acidic pH stress in S. meliloti is versatile and characterized by the differential expression of genes associated with various cellular functions. The purpose of this study was to gain detailed insight into the participation of sigma factors in the complex stress response system of S. meliloti 1021 using pH stress as an effector. 相似文献19.
Stephen W Schaffer Chian Ju Jong Ramila KC Junichi Azuma 《Journal of biomedical science》2010,17(Z1):S2
Taurine (aminoethane sulfonic acid) is an ubiquitous compound, found in very high concentrations in heart and muscle. Although taurine is classified as an amino acid, it does not participate in peptide bond formation. Nonetheless, the amino group of taurine is involved in a number of important conjugation reactions as well as in the scavenging of hypochlorous acid. Because taurine is a fairly inert compound, it is an ideal modulator of basic processes, such as osmotic pressure, cation homeostasis, enzyme activity, receptor regulation, cell development and cell signalling. The present review discusses several physiological functions of taurine. First, the observation that taurine depletion leads to the development of a cardiomyopathy indicates a role for taurine in the maintenance of normal contractile function. Evidence is provided that this function of taurine is mediated by changes in the activity of key Ca2+ transporters and the modulation Ca2+ sensitivity of the myofibrils. Second, in some species, taurine is an established osmoregulator, however, in mammalian heart the osmoregulatory function of taurine has recently been questioned. Third, taurine functions as an indirect regulator of oxidative stress. Although this action of taurine has been widely discussed, its mechanism of action is unclear. A potential mechanism for the antioxidant activity of taurine is discussed. Fourth, taurine stabilizes membranes through direct interactions with phospholipids. However, its inhibition of the enzyme, phospholipid N-methyltransferase, alters the phosphatidylcholine and phosphatidylethanolamine content of membranes, which in turn affects the function of key proteins within the membrane. Finally, taurine serves as a modulator of protein kinases and phosphatases within the cardiomyocyte. The mechanism of this action has not been studied. Taurine is a chemically simple compound, but it has profound effects on cells. This has led to the suggestion that taurine is an essential or semi-essential nutrient for many mammals. 相似文献
20.
Julia Bolsinger Andrzej Pronczuk KC Hayes 《The Journal of nutritional biochemistry》2013,24(11):1945-1952
Amount and type of dietary carbohydrate (CHO), as well as the CHO:fat ratio, are thought to be critical for both the rate of development and severity of Type 2 diabetes mellitus. Thus, these nutritional considerations were examined in the previously described “spontaneous” model of diabetes and metabolic syndrome, the Nile rat. Weanling male Nile rats (n=92) were fed semipurified diets, modifying glycemic index and load by changing the amount of fiber or altering the CHO:fat ratio. Random and fasting blood glucose and body weight were assessed, and diabetes was characterized in terms of blood glucose, relevant plasma and liver parameters, food and water intake and terminal organ weights. Nile rats fed with hiCHO became more hyperglycemic than rats fed with modCHO (P<.05), while loCHO and hiCHO+hiFiber rats remained essentially normoglycemic. Liver lipid and glycogen accumulation was associated with severe hyperlipemia in diabetic rats, analogous to metabolic syndrome in humans. Advanced diabetes was linked to liver and kidney damage and elevated blood urea nitrogen with weight loss. Dispersing dietary CHO by fiber or replacing it by moderate fat (reducing the glycemic index and load) delayed the onset of diabetes but did not prevent signs of insulin resistance. A very low content of dietary CHO (high fat) seemed to prevent even these early indicators of insulin resistance. Thus, the Nile rat represents a novel CHO-sensitive model for study of Type 2 diabetes that reliably follows the course of disease in humans. 相似文献