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Calcium-calcineurin signaling pathway in Candida albicans: A potential drug target.
Li, W, Shrivastava, M, Lu, H, Jiang, Y
Microbiological research. 2021;:126786
Abstract
Increased morbidity and mortality of candidiasis are a notable threat to the immunocompromised patients. At present, the types of drugs available to treat C. albicans infection are relatively limited. Moreover, the emergence of antifungal drug resistance of C. albicans makes the treatment of C. albicans infection more difficult. The calcium-calcineurin signaling pathway plays a crucial role in the survival and pathogenicity of C. albicans and may act as a potential target against C. albicans. In this review, we summarized functions of the calcium-calcineurin signaling pathway in several biological processes, compared the differences of this signaling pathway between C. albicans and humans, and described anti-C. albicans activity of inhibitors of this signaling pathway. We believe that targeting the calcium-calcineurin signaling pathway is a promising strategy to cope with C. albicans infection.
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Enhanced SA and Ca2+ signaling results in PCD-mediated spontaneous leaf necrosis in wheat mutant wsl.
Li, H, Jiao, Z, Zhang, P, Ni, Y, Wang, T, Zhang, J, Li, J, Jiang, Y, Yang, X, Li, L, et al
Molecular genetics and genomics : MGG. 2021;(6):1249-1262
Abstract
Leaf is the major photosynthesis organ and the key source of wheat (Triticum aestivum L.) grain. Spotted leaf (spl) mutant is a kind of leaf lesion mimic mutants (LMMs) in plants, which is an ideal material for studying the mechanisms of leaf development. In this study, we report the leaf abnormal development molecular mechanism of a spl mutant named white stripe leaf (wsl) derived from wheat cultivar Guomai 301 (WT). Histochemical observation indicated that the leaf mesophyll cells of the wsl were destroyed in the necrosis regions. To explore the molecular regulatory network of the leaf development in mutant wsl, we employed transcriptome analysis, histochemistry, quantitative real-time PCR (qRT-PCR), and observations of the key metabolites and photosynthesis parameters. Compared to WT, the expressions of the chlorophyll synthesis and photosynthesis-related homeotic genes were repressed; many genes in the WRKY transcription factor (TF) families were highly expressed; the salicylic acid (SA) and Ca2+ signal transductions were enhanced in wsl. Both the chlorophyll contents and the photosynthesis rate were lower in wsl. The contents of SA and reactive oxygen species (ROS) were significantly higher, and the leaf rust resistance was enhanced in wsl. Based on the experimental data, a primary molecular regulatory model for leaf development in wsl was established. The results indicated that the SA accumulation and enhanced Ca2+ signaling led to programmed cell death (PCD), and ultimately resulted in spontaneous leaf necrosis of wsl. These results laid a solid foundation for further research on the molecular mechanism of leaf development in wheat.
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Calcium: magnesium intake ratio and colorectal carcinogenesis, results from the prostate, lung, colorectal, and ovarian cancer screening trial.
Zhao, J, Giri, A, Zhu, X, Shrubsole, MJ, Jiang, Y, Guo, X, Ness, R, Seidner, DL, Giovannucci, E, Edwards, TL, et al
British journal of cancer. 2019;(9):796-804
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Abstract
BACKGROUND We aimed to evaluate the associations between calcium and various stages of colorectal carcinogenesis and whether these associations are modified by the calcium to magnesium (Ca:Mg) ratio. METHODS We tested our hypotheses in the prostate lung, colorectal and ovarian cancer screening trial. RESULTS Calcium intake did not show a dose-response association with incident adenoma of any size/stage (P-trend = 0.17), but followed an inverse trend when restricted to synchronous/advanced adenoma cases (P-trend = 0.05). This inverse trend was mainly in participants with Ca:Mg ratios between 1.7 and 2.5 (P-trend = 0.05). No significant associations were observed for metachronous adenoma. Calcium intake was inversely associated with CRC (P-trend = 0.03); the association was primarily present for distal CRC (P-trend = 0.01). The inverse association between calcium and distal CRC was further modified by the Ca:Mg ratio (P-interaction < 0.01); significant dose-response associations were found only in participants with a Ca:Mg ratio between 1.7 and 2.5 (P-trend = 0.04). No associations for calcium were found in the Ca:Mg ratio above 2.5 or below 1.7. CONCLUSION Higher calcium intake may be related to reduced risks of incident advanced and/or synchronous adenoma and incident distal CRC among subjects with Ca:Mg intake ratios between 1.7 and 2.5.
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Effects of Enhanced Exercise and Combined Vitamin D and Calcium Supplementation on Muscle Strength and Fracture Risk in Postmenopausal Chinese Women.
Xue, Y, Hu, Y, Wang, O, Wang, C, Han, G, Shen, Q, Deng, H, Jiang, Y, Li, M, Xia, W, et al
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae. 2017;(3):345-351
Abstract
Objective To observe the effects of enhanced exercise and combined vitamin D and calcium supplementation on muscular strength and fracture occurrence in postmenopausal women with a high risk of osteoporosis.Methods Totally 614 postmenopausal women at high risk factors of osteoporosis were enrolled in Dongcheng district of Beijing and randomized into four groups:group A(control group,n=173),group B(regular Tai Chi exercise,n=171),group C(calcium 600 mg/d+VitD3 800 U/d,n=139),and group D[calcium 600 mg/d+25 hydroxyl vitamin D(25OHD) 0.25 μg/d,n=131].Muscular strength was measured at baseline and one and two years after intervention.Bone turnover markers were measured at baseline and during the two-year follow-up.Falls and fractures were recorded.Results The incidence of 25OHD<50 nmol/L was approximately 92.6%.During the follow-up,the left grip strength decreased significantly two years after intervention(t=-3.252,P=0.001)in group A.Right grip strength decreased significantly in group B(t=2.460,P=0.015)while left grip strength improved significantly in group C(t=-2.051,P=0.043)one year after intervention.In group D,muscular strength in both 12-month and 24-month did not change compared with baseline(both P>0.05).Furthermore,serum procollagen type I N-terminal propeptide elevated significantly in group A(t=-2.962,P=0.004),group B(t=-2.888,P=0.005),and group C(t=-2.441,P=0.016),whereas β-C-terminal telopeptide of type I collagen decreased significantly in group B(t=2.285,P=0.024)and group D(t=2.596,P=0.011)two years after intervention.Conclusion Enhanced exercise and combined calcium vitamin D supplementation may help sustain muscle strength in postmenopausal women,while calcium and vitamin D supplementation may improve muscular strength within a short period of time.
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New insights into the effect of rapid transfusion of fresh frozen plasma on ionized calcium.
Sulemanji, DS, Bloom, JD, Dzik, WH, Jiang, Y
Journal of clinical anesthesia. 2012;(5):364-9
Abstract
STUDY OBJECTIVES 1) To develop an in vitro system to simulate the kinetics of ionized calcium in mixed venous blood during rapid transfusion of fresh frozen plasma (FFP) and 2) to use the in vitro data to estimate the effect of the transfusion rate relative to cardiac output (CO) on ionized calcium. DESIGN Experimental study. SETTING Research laboratory of an academic hospital. MEASUREMENTS Citrated FFP was mixed with compatible heparinized whole blood at various volume ratios in vitro to simulate the mixed venous blood obtained at various flow ratios of FFP transfusion to the recipient's venous system in vivo. Ionized calcium was measured after each mixture. MAIN RESULTS Mixing FFP and whole blood at volume ratios of 0:100, 5:95, 10:90, and 15:85 yielded ionized calcium levels (mean ± SD, mmol/L) of 1.23, 0.81 ± 0.02, 0.54 ± 0.08, and 0.34 ± 0.02, respectively. The 50% reduction in ionized calcium occurred at a volume ratio of 7:93. CONCLUSIONS An instantaneous 50% reduction in ionized calcium occurs in vitro at a proportion equivalent to a transfusion rate of FFP representing 7% of CO.
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Activating mutations of the calcium-sensing receptor: management of hypocalcemia.
Lienhardt, A, Bai, M, Lagarde, JP, Rigaud, M, Zhang, Z, Jiang, Y, Kottler, ML, Brown, EM, Garabédian, M
The Journal of clinical endocrinology and metabolism. 2001;(11):5313-23
Abstract
Activating mutations of the calcium-sensing receptor (CaR) can cause isolated hypoparathyroidism. Treatment of hypocalcemia in these patients remains to be optimized, because the use of 1-hydroxylated vitamin D3 derivatives can cause hypercalciuria and nephrocalcinosis. We identified activating CaR mutations in 8 (42%) of 19 unrelated probands with isolated hypoparathyroidism. The severity of hypocalcemic symptoms at diagnosis was independent of age, mutation type, or mode of inheritance but was related to the degree of hypocalcemia; serum Ca was 1.97 +/- 0.08, 1.82 +/- 0.14, and 1.54 +/- 0.22 mmol/liter, respectively, in asymptomatic (n = 7), mildly symptomatic (n = 8), and severely symptomatic patients (n = 6). Hypocalcemia segregated with the CaR mutation, but no phenotype-genotype relationships were identified. Fourteen patients received regular 1-hydroxylated vitamin D3 treatment (mean duration, 7.2 +/- 4.9 yr). Nine had hypercalciuric episodes, which were associated with nephrocalcinosis in eight cases. Serum Ca during treatment predicted hypercalciuria and nephrocalcinosis poorly, because either or both of the latter could develop in hypocalcemic patients. Thus, mutational analysis of the CaR gene should be considered early in the work-up of isolated hypoparathyroidism. Treatment options should be weighed carefully in patients with serum Ca below 1.95 mmol/liter. The risk of nephrocalcinosis during treatment can be minimized by carefully monitoring urinary Ca excretion.