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Roles of four feedback loops in mitochondrial permeability transition pore opening induced by Ca^{2+} and reactive oxygen species.
Qi, H, Xu, G, Peng, XL, Li, X, Shuai, J, Xu, R
Physical review. E. 2020;(6-1):062422
Abstract
Transient or sustained permeability transition pore (PTP) opening is important in normal physiology or cell death, respectively. These are closely linked to Ca^{2+} and reactive oxygen species (ROS). The entry of Ca^{2+} into mitochondria regulates ROS production, and both Ca^{2+} and ROS trigger PTP opening. In addition to this feedforward loop, there exist four feedback loops in the Ca^{2+}-ROS-PTP system. ROS promotes Ca^{2+} entering (F1) and induces further ROS generation (F2), forming two positive feedback loops. PTP opening results in the efflux of Ca^{2+} (F3) and ROS (F4) from the mitochondria, forming two negative feedback loops. Owing to these complexities, we construct a mathematical model to dissect the roles of these feedback loops in the dynamics of PTP opening. The qualitative agreement between simulation results and recent experimental observations supports our hypothesis that under physiological conditions the PTP opens in an oscillatory state, while under pathological conditions it opens in a high steady state. We clarify that the negative feedback loops are responsible for producing oscillations, wherein F3 plays a more prominent role than F4; whereas the positive feedback loops are beneficial for maintaining oscillation robustness, wherein F1 has a more dominant role than F2. Furthermore, we manifest that the proper increase in negative feedback strength or decrease in positive feedback strength not only facilitates the occurrence of oscillations and thus protects the system against a high steady state, but also assists in lowering the oscillation peak. This study may provide potential therapeutic strategies in treating neurodegenerative diseases due to PTP dysfunction.
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2.
Zinc-Calcium-Fluoride Bioglass-Based Innovative Multifunctional Dental Adhesive with Thick Adhesive Resin Film Thickness.
Yao, C, Ahmed, MH, Li, X, Nedeljkovic, I, Vandooren, J, Mercelis, B, Zhang, F, Van Landuyt, KL, Huang, C, Van Meerbeek, B
ACS applied materials & interfaces. 2020;(27):30120-30135
Abstract
Apart from producing high bond strength to tooth enamel and dentin, a dental adhesive with biotherapeutic potential is clinically desirable, aiming to further improve tooth restoration longevity. In this laboratory study, an experimental two-step universal adhesive, referred to as Exp_2UA, applicable in both the etch-and-rinse (E&R) and self-etch (SE) modes and combining a primer, containing 10-methacryloyloxydecyldihydrogen phosphate as a functional monomer with chemical binding potential to hydroxyapatite, with a bioglass-containing hydrophobic adhesive resin, was multifactorially investigated. In addition to primary property assessment, including measurement of bond strength, water sorption, solubility, and polymerization efficiency, the resultant adhesive-dentin interface was characterized by transmission electron microscopy (TEM), the filler composition was analyzed by energy-dispersive X-ray spectroscopy, and the bioactive potential of the adhesive was estimated by measuring the long-term ion release and assessing its antienzymatic and antibacterial potential. Four representative commercial adhesives were used as reference/controls. Application in both the E&R and SE modes resulted in a durable bonding performance to dentin, as evidenced by favorable 1 year aged bond strength data and a tight interfacial ultrastructure that, as examined by TEM, remained ultramorphologically unaltered upon 1 year of water storage aging. TEM revealed a 20 μm thick hydrophobic adhesive layer with a homogeneous bioglass filler distribution. Adequate polymerization conversion resulted in extremely low water sorption and solubility. In situ zymography revealed reduced endogenous proteolytic activity, while Streptococcus mutans biofilm formation was inhibited. In conclusion, the three-/two-step E&R/SE Exp_2UA combines the high bonding potential and bond degradation resistance with long-term ion release, rendering the adhesive antienzymatic and antibacterial potential.
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3.
Comparison of fracture risk using different supplemental doses of vitamin D, calcium or their combination: a network meta-analysis of randomised controlled trials.
Hu, ZC, Tang, Q, Sang, CM, Tang, L, Li, X, Zheng, G, Feng, ZH, Xuan, JW, Shen, ZH, Shen, LY, et al
BMJ open. 2019;(10):e024595
Abstract
OBJECTIVE Inconsistent findings in regard to association between different concentrations of vitamin D, calcium or their combination and the risk of fracture have been reported during the past decade in community-dwelling older people. This study was designed to compare the fracture risk using different concentrations of vitamin D, calcium or their combination. DESIGN A systematic review and network meta-analysis. DATA SOURCES Randomised controlled trials in PubMed, Cochrane library and Embase databases were systematically searched from the inception dates to 31 December 2017. OUTCOMES Total fracture was defined as the primary outcome. Secondary outcomes were hip fracture and vertebral fracture. Due to the consistency of the original studies, a consistency model was adopted. RESULTS A total of 25 randomised controlled trials involving 43 510 participants fulfilled the inclusion criteria. There was no evidence that the risk of total fracture was reduced using different concentrations of vitamin D, calcium or their combination compared with placebo or no treatment. No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of hip or vertebral fractures. CONCLUSIONS The use of supplements that included calcium, vitamin D or both was not found to be better than placebo or no treatment in terms of risk of fractures among community-dwelling older adults. It means the routine use of these supplements in community-dwelling older people should be treated more carefully. PROSPERO REGISTRATION NUMBER CRD42017079624.
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4.
The Significance of Calcium in Photosynthesis.
Wang, Q, Yang, S, Wan, S, Li, X
International journal of molecular sciences. 2019;(6)
Abstract
As a secondary messenger, calcium participates in various physiological and biochemical reactions in plants. Photosynthesis is the most extensive biosynthesis process on Earth. To date, researchers have found that some chloroplast proteins have Ca2+-binding sites, and the structure and function of some of these proteins have been discussed in detail. Although the roles of Ca2+ signal transduction related to photosynthesis have been discussed, the relationship between calcium and photosynthesis is seldom systematically summarized. In this review, we provide an overview of current knowledge of calcium's role in photosynthesis.
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5.
A Complex Role for Calcium Signaling in Colorectal Cancer Development and Progression.
Wang, W, Yu, S, Huang, S, Deng, R, Ding, Y, Wu, Y, Li, X, Wang, A, Wang, S, Chen, W, et al
Molecular cancer research : MCR. 2019;(11):2145-2153
Abstract
Clinical data suggest that many malignant cancers are associated with hypercalcemia. Hypercalcemia can facilitate the proliferation and metastasis of gastric and colon tumors, and has been considered a hallmark of end-stage disease. However, it has also been reported that dietary calcium or vitamin D supplementation could reduce the risk of many types of cancers. In particular, the intestines can absorb considerable amounts of calcium via Ca2+-permeable ion channels, and hypercalcemia is common in patients with colorectal cancer. Thus, this review considers the role of calcium signaling in the context of colorectal cancer and summarizes the functions of specific regulators of cellular calcium levels in the proliferation, invasion, metastasis, cell death, and drug resistance of colorectal cancer cells. The data reveal that even a slight upregulation of intracellular Ca2+ signaling can facilitate the onset and progression of colorectal cancer, while continuous Ca2+ influx and Ca2+ overload may cause tumor cell death. This dual function of Ca2+ signaling adds nuance to the debate over the hallmarks of colorectal cancer, and may even provide new directions and strategies for clinical interventions.
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6.
Evaluation of anemia and serum iPTH, calcium, and phosphorus in patients with primary glomerulonephritis.
Li, Y, Zhang, W, Ren, H, Wang, W, Shi, H, Li, X, Chen, X, Shen, P, Wu, X, Xie, J, et al
Contributions to nephrology. 2013;:31-40
Abstract
Glomerulonephritis (GN) remains a major cause of morbidity and mortality in chronic kidney disease (CKD). Our study aimed to investigate the prevalence of anemia, abnormal serum intact parathyroid hormone (iPTH), calcium, and phosphorus in a Chinese patient population with primary GN. Medical histories and laboratory test results were collected from 2,924 patients with primary GN hospitalized in Ruijin Hospital of Shanghai between January 2003 and August 2009. The leading cause of CKD was primary glomerular diseases, which were responsible for up to 53.5% of all cases. IgA nephropathy was the most common cause, accounting for 38.7%, followed by focal segmental glomerulosclerosis (FSGS). The anemia rate of GN patients in early stages of CKD (stages 1-2 and 3) was 16-36%, and rapidly accelerated to 65.8 and 80.2% in advanced CKD stage 4 and stage 5, respectively. There was no significant decline observed in the level of serum calcium in patients with CKD stages 1-4 (p > 0.05). However, in patients with CKD stage 5 the prevalence of hypocalcaemia increased significantly (13.7%, p = 0.000). The prevalence of hyperphosphatemia did not significantly increase in patients with CKD stages 1-3 (p < 0.05), but was much higher in patients with CKD stages 4 and 5 (p = 0.001 and p = 0.021, respectively) and showed a negative correlation with renal function. Serum iPTH levels did not increase significantly in GN patients with CKD stages 1-2. The median iPTH levels were 54.7, 88.6, and 289.2 pg/ml (p = 0.000) for CKD stages 3-5, respectively, all of which showed negative correlation with renal function. The proportion of vitamin D insufficiency and deficiency increased to 29.3 and 11.2%, respectively, as the glomerular filtration rate fell below 15 ml/min/1.73 m(2). Primary glomerular disease remains the major cause of CKD in China, and complications such as anemia and metabolic bone disease are frequently present in GN patients.