Paricalcitol in hemodialysis patients with secondary hyperparathyroidism and its potential benefits.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication in patients with end-stage renal disease and it is also common in hemodialysis patients. SHPT can increase bone fragility and calcification of blood vessels and soft tissues, which greatly increases the risk of death. AIM: To discuss the outcome, safety and other potential benefits of paricalcitol injection in hemodialysis patients with SHPT. METHODS: We recruited 40 patients who received hemodialysis at our hospital for chronic renal failure with SHPT between March and December 2019. They received paricalcitol injection for 24 wk (starting dose, 0.06-0.08 µg/kg), three times per week. They were followed up at the baseline (week 0), week 4, week 12 and week 24. The primary outcome indicator was the percentage of patients with a > 30% decrease in intact parathyroid hormone (iPTH) levels at week 24 compared with the baseline. The secondary outcome indicators included percentage decrease in iPTH levels at week 24, standard-reaching rate of iPTH (percentage of patients with iPTH down to 130-585 pg/mL), changes in serum levels of calcium (Ca), phosphate (P), Ca × P product, alkaline phosphatase (ALP), creatinine (Cre), hemoglobin (Hb), and C-reactive protein (CRP), and incidence of adverse events (AEs). RESULTS: After 24 wk of treatment, iPTH levels decreased significantly (598.88 ± 381.29 pg/mL vs 888.84 ± 376.88 pg/mL, P < 0.05). More than 30% decrease of iPTH was found in 21 of 36 (58.33%) patients. The average decrease in iPTH levels was 32.16 ± 4.33%; the standard-reaching rate of iPTH levels was 66.67% (24/36); and ALP levels decreased significantly compared with the baseline (113.72 ± 41.73 IU/L vs 133.45 ± 56.86 IU/L) (t = 2.798, P < 0.05). There were no significant differences in the serum levels of calcium, Hb, Cre and CRP compared with the baseline (P > 0.05). After 24 wk of treatment, serum P levels decreased compared with the baseline (1.91 ± 0.40 mmol/L vs 2.16 ± 0.66 mmol/L) (t = 2.830, P < 0.05). Ca × P product decreased significantly compared with the baseline (56.38 ± 13.22 mg2/dL2 vs 63.97 ± 20.30 mg2/dL2) (t = 2.717, P < 0.05). No serious adverse events occurred. CONCLUSION: Paricalcitol was a safe and effective treatment for hemodialysis patients with SHPT. It decreased serum levels of iPTH, ALP and P and maintained stability of serum Ca levels.

FBW7 targets KLF10 for ubiquitin-dependent degradation.

FBW7, a key component of SCFFBW7 E3 ubiquitin ligase, targets various proteins for degradation via the conserved Cdc4 phosphodegron (CPD) in substrates. In this study, we report that KLF10 is degraded by FBW7 via a conserved CPD. Through systematic analysis of the degradation of KLF transcription factors by FBW7, we identified KLF10 as a novel degradation target of FBW7. Ectopic expression of FBW7 markedly promoted the degradation of KLF10 while knockdown of endogenous FBW7 increased the protein levels of KLF10. In addition, simultaneous mutations of both threonine 82 (T82) and serine 86 (S86) significantly reduced the FBW7-mediated KLF10 degradation. Moreover, KLF10 containing a conserved putative CPD (TPPXSP) from amino acids 82 to 87, directly interacted with WD40 domain of FBW7 in a phosphorylation-dependent manner. Importantly, FBW7 could reverse the KLF10-mediated inhibition of Smad7 activity. Thus, our study uncovers a novel regulatory mechanism underlying which KLF10 stability and its biological function are mediated by FBW7.

µ-α-Methyl-glutarato-bis-{aqua-[bis-(2-pyridylcarbon-yl)aminato]copper(II)} trihydrate.

In the title compound, [Cu(2)(C(12)H(8)N(3)O(2))(2)(C(6)H(8)O(4))(H(2)O)(2)]·3H(2)O, both crystallographically independent Cu atoms are in similar distorted square-pyramidal coordination environments. The dinuclear complex mol-ecules are assembled into one-dimensional supra-molecular chains extending in the [100] direction by hydrogen bonds. Inter-chain hydrogen bonds further link these chains into layers perpendicular to [001].

A planar cyclic hexamer of water molecules in dichlorido(2,4,6-tri-2-pyridyl-1,3,5-triazine)cadmium(II) trihydrate.

In the title compound, [CdCl2(C(18)H(12)N(6))].3H2O, the Cd atom has a distorted square-pyramidal coordination geometry. The solvent water molecules are hydrogen bonded to each other to form planar cyclic water hexamers, which, together with other hydrogen bonds, interlink the Cd complex molecules to give one-dimensional supramolecular ribbons that extend along the [111] direction. The chains are assembled into two-dimensional layers parallel to (111) by pi-pi stacking interactions. Furthermore, interlayer pi-pi stacking interactions and weak C-H...Cl hydrogen bonds complete the formation of a three-dimensional framework.