Circulating spexin levels are influenced by the presence or absence of gestational diabetes.

The study aimed to determine whether circulating spexin (SPX) is modified during the course of pregnancy and whether it is affected by the presence of glucose intolerance, i.e., Gestational Diabetes Mellitus (GDM). This prospective study included 102 pregnant women (63 non-GDM and 39 GDM; mean age 29.4 ±â€¯5.1 years; mean BMI 28.0 ±â€¯6.1 kg/m2). Anthropometrics, glycemic and lipid profiles, as well measurements of circulating adipocytokines and SPX were measured at baseline and after 3 and 6 months. In GDM patients, SPX levels increased significantly after 6-months, in parallel with a borderline significant increase in glucose (p = 0.07). In non-GDM patients, however, median SPX level decreased from baseline to 6-months (p < 0.01), and this change was not associated with changes in glucose levels. Change in glucose from baseline to 6-months was positively associated with change in SPX in GDM patients only (R = 0.37; p < 0.05). SPX levels are positively influenced by glucose intolerance in pregnant women with GDM, while they decrease in control women without GDM.

Small-Molecule Inhibition of CBX4/7 Hypersensitises Homologous Recombination-Impaired Cancer to Radiation by Compromising CtIP-Mediated DNA End Resection.

The therapeutic targeting of DNA repair pathways is an emerging concept in cancer treatment. Compounds that target specific DNA repair processes, such as those mending DNA double-strand breaks (DSBs), are therefore of therapeutic interest. UNC3866 is a small molecule that targets CBX4, a chromobox protein, and a SUMO E3 ligase. As a key modulator of DNA end resection-a prerequisite for DSB repair by homologous recombination (HR)-CBX4 promotes the functions of the DNA resection factor CtIP. Here, we show that treatment with UNC3866 markedly sensitises HR-deficient, NHEJ-hyperactive cancer cells to ionising radiation (IR), while it is non-toxic in selected HR-proficient cells. Consistent with UNC3866 targeting CtIP functions, it inhibits end-resection-dependent DNA repair including HR, alternative end joining (alt-EJ), and single-strand annealing (SSA). These findings raise the possibility that the UNC3866-mediated inhibition of end resection processes we define highlights a distinct vulnerability for the selective killing of HR-ineffective cancers.

Favorable Changes in Fasting Glucose in a 6-month Self-Monitored Lifestyle Modification Programme Inversely Affects Spexin Levels in Females with Prediabetes.

Spexin (SPX) is a novel peptide thought to have a role in various metabolic regulations. Given its presumed body-weight regulatory functions, we aimed to determine whether lifestyle intervention programs on weight loss and fasting glucose (FG) improvement among people with impaired glucose regulation also alter levels of circulating SPX. A total of 160 Saudi adult males and females with prediabetes were randomly selected from a larger cohort (N = 294) who underwent a 6-month lifestyle modification program to improve their glycemic status. Participants were split into two groups based on differences in glucose levels post-intervention, with the first 50% (improved group) having the most significant reduction in FG. SPX was measured at baseline and after 6 months. Changes in SPX was significant only in the improved group [baseline: median (Q1-Q3) of 164 pg/ml (136-227) vs follow-up: 176 pg/ml (146-285); p < 0.01]. When stratified by sex, the significant increase was observed only in females [159 pg/ml (127-252) vs 182.5 (152,369.1); p < 0.01]. Furthermore, SPX levels showed a significant inverse association with FG (ß = -0.22, p = 0.003) even after adjustment with age and BMI, again only in females. Circulating SPX levels increase over time in people with prediabetes, particularly women who responded favorably in a 6-month lifestyle intervention program. Whether an unknown mechanism regulating the sexual disparity seen in SPX levels post-intervention exists should be further investigated using a larger sample size.

Spexin Levels Are Associated with Metabolic Syndrome Components.

BACKGROUND: Spexin (SPX) is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in adults' overall cardiometabolic health. The aim of the study was to determine whether circulating levels of spexin (SPX) is associated with components of metabolic syndrome (MetS). METHODS: The present cross-sectional study included 124 participants (41 males and 83 females; aged 42.4 ± 10.3 y) (MetS group) and 136 (21 male and 115 females; aged 33.1 ± 8.7 y) (non-MetS group). SPX was measured using commercially available assays. Anthropometrics were measured, and fasting serum glucose levels as well as lipid profile were quantified routinely. MetS was screened according to common definitions. RESULTS: SPX levels were significantly lower in participants with MetS vs. non-MetS (0.18 ng/ml (0.13-0.24) vs. 0.26 ng/ml (0.17-0.50); p < 0.001). In all MetS definitions used, SPX was significantly lower in the MetS group than the non-MetS group using the WHO definition after adjustment for age and BMI. Stratification according to sex revealed that SPX was associated with MetS only in women, and this significance was lost after adjustment for age and BMI. CONCLUSIONS: Lower circulating levels of SPX in adults are modestly associated with components of MetS and are sex-specific. Further studies are necessary to determine whether SPX is associated with harder outcomes such as atherosclerosis and diabetes in the general population.

Associations of Spexin and cardiometabolic parameters among women with and without gestational diabetes mellitus.

Spexin (SPX) is a novel biomarker abundantly expressed in several animal and human tissues implicated in food intake and glucose control, respectively. As new roles for SPX are emerging, the present study explored for the first time, the associations of SPX to several cardiometabolic indices and inflammatory markers in pregnant women, a demographic not yet investigated with respect to SPX. A total of 117 Saudi women subdivided to those with gestational diabetes mellitus (GDM) (N = 63) and those without (N = 54) were included in this cross-sectional study. Anthropometry, glycemic, lipid, vitamin D, adipocytokines and inflammatory markers were measured consecutively at baseline and after the 2nd and 3rd trimesters. Age- and BMI adjusted comparisons revealed that levels of SPX were not significantly different in pregnant women with and without GDM. In all subjects, circulating levels of SPX showed modest associations with glucose (R = 0.18; p = .08) and HOMA ß (R = -0.19; p = .09) as well as significant positive associations with total cholesterol (R = 0.25; p = .02), LDL-cholesterol (R = 0.25; p = .02), 25(OH)D (R = 0.22; p = .04), albumin (R = 0.30; p < .01) and IL1ß (R = 0.41; p < .01). Stepwise regression analysis also suggested that IL1ß, leptin and albumin were the significant predictors of SPX. In summary, SPX levels modestly affect glucose and insulin sensitivity in pregnant women but is not associated with GDM and obesity. The significant association of SPX to ILß warrants further investigation as to the role of SPX in immune modulation.