A novel tumor-targeted glutathione responsive Glycosylated-Camptothecin nanosupramolecular prodrug (CPT-GL NSp) was designed and fabricated via a disulfide bond. The effects of glycoligand with different polarities on solubility, self-assembly, stability, cellular uptake, and glutathione responsive cleaving were explored, and an optimal glycosylated ligand was selected for nanosupramolecular prodrug. It has been found that CPT-GL NSp exhibited higher drug loading than traditional nanoparticles. Among of which maltose modified NSp had the strongest anti-tumor effects than that of glucose and maltotriose. CPT-SS-Maltose had a similar anti-tumor ability to Irinotecan (IR), but the superior performance in solubility, hemolysis, and uptake of HepG2 cells.

There are few data on pregnancy outcomes in women with pre-diabetes (HbA1c 41-49 mmol/mmol) at pregnancy booking. We aimed to (i) identify the proportion of women in Counties Manukau Health (CMH), South Auckland, New Zealand (NZ), with pre-diabetes at booking and (ii) compare outcomes between women with normal HbA1c and pre-diabetes.
Using data from a multi-ethnic population of 10,869 singleton pregnancies, booked at <20 weeks from January 2017 to December 2018 in CMH, we compared outcomes between those with normal HbA1c (≤40 mmol/mol) and those with pre-diabetes (HbA1c 41-49 mmol/mol). The primary outcomes were gestational diabetes mellitus (GDM) by NZ criteria and large for gestational age (LGA) defined as birthweight >90th customised centile. Logistic regression determined the contribution of HbA1c 41-49 mmol/mol to the development of GDM.
Among 10,869 participants, 193 (1.78%) had an HbA1c 41-49 mmol/mol at <20 weeks\' gestation. Those with HbA1c 41-49 mmol/mol were 11 times more likely to develop GDM (59.6 vs 7.9%; adjusted odds ratio (aOR) 11.16 (7.59, 16.41)) and were more likely to have an LGA baby (47 (24.4%) vs 1436 (13.5%) aOR 1.63 (1.10, 2.41)) versus those with normal HbA1c. They also had significantly higher rates of pre-eclampsia, caesarean sections, preterm births and perinatal deaths.
Nearly two-thirds of women with a booking HbA1c of 41-49 mmol/mmol developed GDM as well as multiple other perinatal complications compared to women with HbA1c ≤40. Trials to evaluate the impact of treatment in early pregnancy on the risk of late-pregnancy complications are required.

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UNASSIGNED: Annonaceous acetogenins (ACGs) are secondary metabolites produced by the Annonaceae family and display potent anticancer activity against various cancer cell lines. Squamocin and bullatacin are two examples of ACGs that show promising antitumor activity; however, preclinical data are not sufficient partly due to their being highly lipophilic and poorly soluble in water. These compounds also display high toxicity to normal cells. Due to these disadvantageous properties, the therapeutic potential of squamocin and bullatacin as antitumor agents has not been fully evaluated.
UNASSIGNED: In order to enhance their water solubility and potentially improve their cancer targeting, squamocin and bullatacin were conjugated to a glucose or galactose to yield glycosylated derivatives by direct glycosylation or the Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction (the click reaction). The synthesized compounds were evaluated for their anticancer property against HeLa, A549 and HepG2 cancer cell lines using MTT assay.
UNASSIGNED: Nine glycosyl derivatives were synthesized and structurally characterized. Most of them show comparable in vitro cytotoxicity against HeLa, A549 and HepG2 cancer cell lines as their parent compounds squamocin and bullatacin. It appears that the type of sugar residue (glucose or galactose), the position at which the sugar residue is attached, and whether or not a linking spacer is present do not affect the potency of these derivatives much. The solubility of galactosylated squamocin 13 in phosphate buffer saline (PBS, pH = 7) is greatly improved (1.37 mg/mL) in comparison to squamocin (not detected in PBS).
UNASSIGNED: The conjugation of a glucose or galactose to squamocin and bullatacin yields glycosyl derivatives with similar level of anticancer activity in tested cell lines. Further studies are needed to demonstrate whether or not these compounds show reduced toxicity to normal cells and their therapeutic potential as antitumor agents.

OBJECTIVE: To evaluate the potential role of glycosylated haemoglobin (HbA1C) as an early biomarker for gestational diabetes.
METHODS: In a retrospective analysis, healthy women who went on to give birth to a singleton newborn in a tertiary medical center in Petach Tikva, Israel, underwent measurement of HbA1C in the first trimester (up to 12 weeks of pregnancy) between August 1, 2007, and December 31, 2014. Women with type 1 or type 2 diabetes, HbA1C ≥6.5%, and/or fasting plasma glucose ≥126 mg/dL were excluded, as were women whose glucose levels had already been tested before 24 weeks of pregnancy. Data were extracted from a maternal and neonatal database. The primary outcome measure was the association between first trimester HbA1C and adverse pregnancy outcome, primarily, gestational diabetes.
RESULTS: The cohort included 142 women. HbA1C concentration was linearly and inversely correlated to length of gestation (r=-0.317, P<0.001). Higher HbA1C was associated with gestational diabetes. An HbA1C concentration of ≥5.45% predicted gestational diabetes with 83.3% sensitivity, 69% specificity, and gave positive and negative predictive values of 53% and 90.8%, respectively.
CONCLUSIONS: Early pregnancy HbA1C could serve as a predictor of gestational diabetes. Ideally, HbA1C should be considered in multi-parameter prediction models to enhance accuracy.

The glycosylated acetylsalicylic acid was prepared with bromo-α-d-galactose and acetylsalicylic acid. It indicated that the glycosylated acetylsalicylic acid had lower cytotoxicity than underivatized acetylsalicylic acid, and might selectively display anticancer activity in this situation that had enzyme or no enzyme.

OBJECTIVE: Diabetes mellitus is an important risk factor for erectile dysfunction (ED). Penile prosthesis implantation surgery is the final solution for diabetic patients with ED, but infections thereof are still a serious risk factor. While some studies suggest that most infections associated with penile prosthesis implantation are associated to high glycated hemoglobin (HbA1c) levels, other research did support such relationship.
METHODS: The current study assessed retrospectively, the association between HbA1c level and penile prosthesis surgery infection. We retrieved and reviewed the records of 300 diabetic patients who had penile prosthesis surgery at our Institution (January 2012-November 2016). Patients\' mean age was 55.26 ± 10.9 years (31% patients were <50 years of age), and mean HbA1c was 7.60 ± 1.90%.
RESULTS: Infection rate among diabetics was 0.67%. Prevalence of prosthesis infection among patients with HbA1c ≤ 9% was 0.9%, compared with 0% among patients with HbA1c > 9%. Prosthesis infection risk did not significantly increase with higher HbA1c levels, with no meaningful difference in the median or mean level of HbA1c in the infected and non-infected diabetic patients.
CONCLUSIONS: Findings do not support the use of HbA1c values among diabetic patients who are candidates for penile prosthesis implantation surgery in order to identify and exclude those who might be prone to increased risk of prosthesis infections. Future studies would benefit from larger sample sizes in order to support or refute our findings.

The carotid intima media thickness (cIMT) and carotid plaque score (cPS) are respective markers of early and late stage subclinical atherosclerosis. Relationships between some laboratory parameters and subclinical atherosclerosis are not yet clear in community dwelling individuals and non-diabetic subjects, so we try to elucidate these relationships and find a model to predict early and late stage subclinical atherosclerosis.
We examined relationships of the cIMT and cPS with different laboratory and demographic data of 331 subjects from a community-based prospective cohort study, using univariate and multivariate analyses.
In regression models and after multiple adjustments, only systolic blood pressure (SBP), age, glycated hemoglobin (HBA1c), and waist circumference (WC) were determinants of the cIMT, and only age, SBP, HBA1c, and blood urea nitrogen (BUN) were determinants of a cPS of > 2 in all individuals. Only HBA1c lost its association with regard to predicting the cIMT in non-diabetic subjects.
HBA1c at > 5.9% can determine early and late stage subclinical atherosclerosis in community dwelling individuals, but only late stage subclinical atherosclerosis in non-diabetic subjects.

Background: Association between poor control of glycemia and the onset of microvascular complications in type 2 diabetes mellitus (T2DM) patients is a hard issue. However, it seems that the impact of pharmacological treatment is important only in early stages of diabetic nephropathy. We sought to examine whether intensive glycemic control is associated with improvement of clinical Chronic Kidney Disease (CKD) outcomes compared to standard glycemic control. Methods: Meta-analysis of published and unpublished randomized controlled trials (RCT) and post-hoc analysis of RCTs comparing anti-diabetic drugs and/or insulin (intensive control) vs. dietary measures (standard control) for relevant outcomes related to progression of CKD clinically manifest was undertaken. Summary estimates obtained by random effects model and funnel plots for assessing reporting bias are presented. Results: Our analysis was based on four RCTs representing 27,391 adult T2DM patients with CKD from around the world. The pooled OR for the outcomes of doubling of serum creatinine and need of dialysis were, respectively, of 0.98 with 95% confidence interval (95% CI) 0.81-1.19, and 0.84 with 95% CI 0.69-1.02. The pooled OR for the outcome of death from kidney failure was 0.62 with 95% CI 0.39-0.98. Clinical differences between studies were not translated in statistical heterogeneity. Reporting bias may be present. Conclusions: Intensive glycemic control has an effect on death from kidney failure compared to standard glycemic control. Better comprehension of glycemic control effects on both T2DM patients with and without CKD is important for individualization of these two treatment modalities.

This sub-analysis of the Iran-AFECT study was to determine the baseline characteristics are predicting the likelihood of attainment of HbA1c goal and changing in HbA1c after initiation of basal insulin glargine in insulin naïve people with type 2 diabetes not adequately controlled with oral glucose-lowering drugs. Iran-AFECT was a 24-week, prospective, multicenter, observational study of people with type 2 diabetes initiated or switched to insulin glargine. In this sub-analysis, we included all insulin naïve people. Glycemic response was defined as HbA1c≤7.0% and/or change in HbA1c at week 24. Data on 433 participants were included. The mean HbA1c was 8.9%±0.9% at baseline which decreased to 7.6%±1.2% (P<0.001). By week 24, 36% of the participants reached HbA1c≤7.0%. In univariate analysis, the strongest association was for the baseline HbA1c (r2=0.32, P<0.001). In multivariate analysis, predictors of change in HbA1c were baseline HbA1c (r2=0.29, P<0.001), and dosing of glargine (r2=0.01, P=0.02). The baseline HbA1c was accounting for 88% of explainable variances in HbA1c. The best cut-off predicting glycemic response for baseline HbA1c was 8.5%. Among factors predicting response to initiating basal insulin therapy with insulin glargine, baseline HbA1c is the strongest predictor explaining most of the variances in HbA1c change.