IGF and IGFBP as an index for discrimination between vitamin D supplementation responders and nonresponders in overweight Saudi subjects.

Vitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25(OH)D level <50 nmol/L), aged 40.4 ±â€Š11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population.

Proteomics Profiling of CLL Versus Healthy B-cells Identifies Putative Therapeutic Targets and a Subtype-independent Signature of Spliceosome Dysregulation.

Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell cancer exhibiting a wide spectrum of disease courses and treatment responses. Molecular characterization of RNA and DNA from CLL cases has led to the identification of important driver mutations and disease subtypes, but the precise mechanisms of disease progression remain elusive. To further our understanding of CLL biology we performed isobaric labeling and mass spectrometry proteomics on 14 CLL samples, comparing them with B-cells from healthy donors (HDB). Of 8694 identified proteins, ∼6000 were relatively quantitated between all samples (q<0.01). A clear CLL signature, independent of subtype, of 544 significantly overexpressed proteins relative to HDB was identified, highlighting established hallmarks of CLL (e.g. CD5, BCL2, ROR1 and CD23 overexpression). Previously unrecognized surface markers demonstrated overexpression (e.g. CKAP4, PIGR, TMCC3 and CD75) and three of these (LAX1, CLEC17A and ATP2B4) were implicated in B-cell receptor signaling, which plays an important role in CLL pathogenesis. Several other proteins (e.g. Wee1, HMOX1/2, HDAC7 and INPP5F) were identified with significant overexpression that also represent potential targets. Western blotting confirmed overexpression of a selection of these proteins in an independent cohort. mRNA processing machinery were broadly upregulated across the CLL samples. Spliceosome components demonstrated consistent overexpression (p = 1.3 × 10-21) suggesting dysregulation in CLL, independent of SF3B1 mutations. This study highlights the potential of proteomics in the identification of putative CLL therapeutic targets and reveals a subtype-independent protein expression signature in CLL.

Sex-specific expression of apolipoprotein levels following replenishment of vitamin D.

Numerous studies have been done to establish the relationship between vitamin D and lipids, yet a definitive causal link is not found. This interventional study aims to evaluate and compare levels of apolipoproteins among vitamin D deficient subjects at baseline and after they achieved full vitamin D status correction.120 Saudi adults with vitamin D deficiency [25(OH)D < 50nmol/l] were recruited and given 50,000IU cholecalciferol weekly for first 2 months, then twice a month for next 2 months, followed by daily 1000IU until month 6. Blood samples were taken at baseline and after 6 months. Serum 25(OH)D, lipid profile and apolipoproteins (A1, A2, B, C1, C2, C3, E and H) were analyzed using commercially available kits. Overall, serum 25(OH)D increased significantly(63.3 ±â€¯16.5nmol/l at end of study vs. 32.5 ±â€¯10.8 at baseline; p < 0.0001). In parallel, a significant increase in apolipoproteins C1, C2, C3 and E (all p-values < 0.01) and a significant decrease in apolipoprotein B (p = 0.02) was observed. Following, stratification according to sex, apolipoproteins C2 and C3 significantly increased only in males (p-values < 0.01) while apolipoprotein C1 significantly increased only in females (p < 0.01). In addition, apolipoprotein B significantly decreased only in females (p = 0.002). These results suggests role of vitamin D in modulation of circulating levels of lipoproteins. The sexual dimorphism observed in circulating levels of measured apolipoproteins following vitamin D correction may explain, in part, known sexual disparity in the events of cardiometabolic health.