Translational Metabolic Syndrome Research最新文献

Background

Currently, a new branch of medicine – glycomedicine – is starting to show the important role of carbohydrates and their interaction with macromolecules in the pathogenesis of many diseases. Their roles in respiratory system diseases development are not an exception.

Review aims

In this review we tried to determine current views on the roles of glycans, glycation products and their receptors in the pathogenesis of respiratory system diseases; opportunities of using these biological molecules for diagnostics, verification of risk and severity; feasible usage as therapeutic targets in respiratory disease treatment.

Conclusion

Glycoscience researches show that glycans play an important role in progression of respiratory system disease. Thus, levels of advanced glycation-end products (AGE) and their receptors (RAGE) are independent risk factors for respiratory system diseases. Moreover, elevated expression intensity of RAGE is usually associated with an increased tumor malignancy, severity of chronic obstructive pulmonary disease (COPD) and bronchial asthma.

Sialic acid-binding immunoglobulin-type lectins (Siglecs) can significantly influence severity of COVID-19 and common pulmonary diseases. Listed molecules can be used both for diagnostic and therapeutic goals, opening up new perspectives for pharmacological treatment. It is worthwhile to note that numerous molecular-biological aspects of glycans' and glycation products' effects on respiratory diseases development are unexplored despite tangible progress in glycoscience.

A substantial number of patients with cardiovascular disease do not take their medications as prescribed. This can lead to an increased risk of disease complications, hospitalisations and death. Therefore, it is necessary to determine methods to detect non-adherence in patients accurately to ensure that patients can be identified and engaged with. This will allow adequate support to be provided to these patients to improve adherence rates and thus lead to better disease outcomes.

This review looks at a wide range of methods to establish medication non-adherence. There is a particular focus on chemical adherence testing as this method has gained acceptance in use in many hypertension clinics and has been recommended by European guidelines for use in patients with suspected resistant hypertension.

This review goes onto discuss the use of chemical adherence testing in hypertension clinics currently and also discusses some of the reasons behind non-adherence and provides solutions that can be discussed with the patients to overcome these challenges. The discussion between the clinician and the patient regarding the chemical adherence test result needs to be held in a no-blame environment to ensure that the patient can engage in an open and honest discussion with the clinician. More training is required for clinicians and healthcare professionals to ensure they feel confident to discuss adherence with their patients.

Even though chemical adherence testing is being used increasingly as the first-choice method to determine non-adherence, more research is required to increase uptake of chemical adherence testing in a wider range of settings.

Spondyloarthritis (SpA) is a group of chronic inflammatory arthritic diseases causing inflammatory back pain and stiffness, leading to irreversible damage of joint and spine, seriously affecting the quality of life. However, the exact pathogenesis of SpA is still unknown, although the blockers of tumor necrosis factor (TNF) are a major therapeutic advance. Of interest is the association between SpA and Immunoglobulin G (IgG) N-glycosylation. IgG N-glycosylation is a process of post-translational modification (PTM) that takes part in regulating anti- and pro-inflammatory effects. A relationship between IgG N-glycosylation and the development of inflammatory arthritic diseases exists, in addition this relationship often occurs before the onset of disease. There are studies reporting the association between IgG N-glycosylation and SpA, leading to a significant amount of data being generated. Analysis of this data in a rigorous form is greatly needed, hence this review will focus on identifying the relationships that exist between IgG N-glycosylation in inflammatory arthritis. More specifically, the modification to the structure of IgG N-glycosylation via TNF blockers as a treatment, the link between disease activity and IgG N-glycosylation, and the predictive capacity of IgG N-glycosylation in SpA. Investigation of IgG N-glycosylation has demonstrated that IgG N-galactosylation plays an important role in the development and prognosis of SpA. This association provides a novel pathway to further research to improve early diagnosis and possible biomarkers for treatment of patients with SpA.

Background

Medicinal herbs have received attention as an alternative to prescription medications. Diabetes mellitus is a chronic disease that affects the normal metabolic pathways in several organs. The purpose of this study was to determine the metabolites responsible for the antiglycogenolytic and glycogenic effects of a hydroethanolic extract of Senna alata L in an experimental model of diabetes mellitus; the male albino Wister rat treated with streptozotocin.

Results

The therapeutic effects of Glibenclamide (0.6 mg/kg body weight) and S. alata L (400 mg/kg body weight) extracts were compared. The oral administration of this extract to diabetic rats resulted in a significant decrease in the levels of glycogenolytic factors that included: glycogen phosphorylase, glucose 6 phosphatase, glycosylated haemoglobin, and lactate dehydrogenase, and a significant increase in the levels of glycogenic factors such as plasma insulin, glycogen synthase, liver glycogen, hexokinase, pyruvate kinase After administration of the plant extract, the observed changes in the activities of these factors were found to be statistically significant and returned to near-normal levels. Additionally, the S. alata extract increased muscle and liver glycogen levels, demonstrating S. alata L's anti-diabetic properties. HPLC analysis identified Kaempferol 3–O–gentiobioside, while GCMS analysis showed the presence of phytol, stigmasterol, sitosterol, dimethyl derivatives, methyl esters, and octanoic acid derivatives.

Conclusion

This work provides experimental evidence for the anti-diabetic potential of S. alata extract, which may result from the existence of beneficial bioactive chemicals. The aberrant metabolic enzymes in streptozotocin-induced diabetic rats' livers were restored following regular treatment with S. alata extract. As a result, S. alata leaves can affect blood glucose levels.

Background

Vitamin D deficiency is now very common globally. Although ultraviolet B (UVB) light dermal exposure is an important endogenous source of vitamin D, dietary supplementation and routine food fortification are of benefit for increasing serum 25-hydroxyvitamin D [25(OH)D]. However, there remains a high prevalence of vitamin D deficiency (~40 in Europe and 62% in Iran). We have designed a two-phase study including the production of nano-encapsulated vitamin D3, an assessment of its stability after fortifying dairy products, and a human trial evaluating the effects of fortified dairy products on the physical and mental health of participants.

Methods

and design: We established the optimal nanocapsule structure for vitamin D fortification of the various dairy products. The second phase of the study was performed as a ten-week, quadruple-blind randomized controlled trial, where milk and yogurt were fortified with vitamin D-containing nano-capsules, with active and control products being distributed to adult participants living in the City of Mashhad.

Preliminary results

Among 346 subjects who intended to participate in our study, 306 participants were selected according to inclusion criteria. At the end of the trial, seventeen subjects were excluded (with a dropout rate of 5.5%). The mean age of the eligible participants was 41.82 ± 7.81 (51.8% being women). Waist circumferences were 102.59 ± 7.74 and 89.39 ± 7.0 for men and women, respectively. There were no significant differences for weight, waist circumference, BMI, energy intake, and physical activity between the four groups at baseline assessments.

Discussion

This study will be the first RCT determining the efficacy of vitamin D fortification in dairy products using nano encapsulation technology on several aspects of physical and mental health. The sample size and high quality of methodology of this study demonstrate the feasibility and benefits of nanotechnology in the food fortification industry and general health in the population.

The trial registration details

registry name: The National Institute for Medical Research Development (NIMAD), registration number: IRCT20101130005280N27, date of registration: 3.9.2018 and the trial was prospectively registered.

Aims

To investigate the mechanism of hyperglycaemia in women with Polycystic Ovary Syndrome (PCOS) by modelling physiological insulin secretion.

Methods

45 non-diabetic women with PCOS (defined by Rotterdam criteria) and 47 controls were studied. Insulin secretion was modelled from glucose and C-peptide concentrations during a 6-point oral glucose tolerance test (OGTT) and insulin resistance (IR) was determined by the Matsuda Insulin Sensitivity Index (ISI).

Results

(1). β-Cell Glucose Sensitivity (βCGS) is not intrinsically impaired in PCOS, but IR is increased. (2) However, women with PCOS and 2-hour hyperglycaemia (glucose >7.5 mmol/l]) were characterized by worse βCGS compared with women with 2-hour glucose <7.5 mmol/l (mean [SD]) 43.5 [23.6] versus 109.0 [68.5] pmol/min/ml/mmol; p = 0.04), and had higher waist circumference (116.8 [15.8] vs 93.5 [15.9] cm; p < 0.01) and 120 minute insulin concentrations (964.0 [579.2–1214.7] vs 328.2 [242.2–475.7] pmol/l; p = 0.01). (3). In contrast, lean, insulin sensitive women with PCOS were euglycemic, even in the presence of poor βCGS, and exhibited favourable cardiometabolic risk profiles.

Conclusions

βCGS is not intrinsically impaired in PCOS, but it is the critical determinant of hyperglycaemia. Women with low βCGS, who also have central adiposity and IR exhibit 2-hour hyperglycaemia, whereas women with high βCGS are able to maintain euglycaemia despite central adiposity and IR. These findings show that (i) waist circumference and 2-hour glucose identify women at higher risk of diabetes, and confirm that (ii) obesity and IR are the key reversible targets for diabetes prevention in women with PCOS.

The purpose of the current study was to investigate the differences and correlations between fatigue levels and blood glucose in individuals with and without diabetes, using psychometric and metabolic assessment of participants. The findings of the present study were that individuals with diabetes are susceptible to fatigue as measured by the Fatigue Severity Scale and the Checklist Individual Scale. Additionally, individuals with fatigue were found to be more susceptible to sleepiness and had overall lower poor sleep quality than those without diabetes as measured by the Karolinska Sleepiness Scale, the Epworth Sleepiness Scale and the Pittsburgh Sleep Quality index (<0.05).

Epigenetic modifications including DNA methylation have been shown to be involved in the fetal programming of disease. Previous animal studies have shown that reduced expression of the ILDR2 gene is associated with diabetes, dyslipidaemia and hepatic steatosis. Using fetal cord blood from obese and normal weight mothers, we identified differential methylation of the ILDR2 gene. This was associated with significant changes in ILDR2 mRNA expression, and changes in neonatal body weight. Our findings suggest that the offspring of obese mothers are at increased risk of metabolic consequences, and that epigenetic regulation of the ILDR2 gene may be involved.

In recent decades, a classic recipe in traditional Chinese medicine, Guilu erxian jiao (GEJ), has been used in the prevention and treatment of myelosuppression following cancer chemotherapy. However, the safety and efficacy of GEJ has not been studied. In the present study, we investigated the safety and efficacy of GEJ in the management of myelosuppression in a cohort of advanced lung adenocarcinoma patients who received 4 cycles of chemotherapy. Treatment with GEJ was compared to the conventional treatment with pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF). The GEJ treatment group (38 patients) was orally administered GEJ whilst the control group (25 patients) were treated with PEG-rhG-CSF during the 4 cycles of chemotherapy. We found that GEJ was as safe as the recommended treatment, PEG-rhG-CSF. GEJ patients recovered from suppressed bone marrow in a much steadier approach, compared with the highly fluctuating changes observed in PEG-rhG-CSF treatment. Our data suggests that GEJ may be a better alternative to manage cancer chemotherapy-induced myelosuppression.