Association of amino acid metabolites with osteoporosis, a metabolomic approach: Bushehr elderly health program.

INTRODUCTION AND OBJECTIVES: Amino acids are the most frequently reported metabolites associated with low bone mineral density (BMD) in metabolomics studies. We aimed to evaluate the association between amino acid metabolic profile and bone indices in the elderly population. METHODS: 400 individuals were randomly selected from 2384 elderly men and women over 60 years participating in the second stage of the Bushehr elderly health (BEH) program, a population-based prospective cohort study that is being conducted in Bushehr, a southern province of Iran. Frozen plasma samples were used to measure 29 amino acid and derivatives metabolites using the UPLC-MS/MS-based targeted metabolomics platform. We conducted Elastic net regression analysis to detect the metabolites associated with BMD of different sites and lumbar spine trabecular bone score, and also to examine the ability of the measured metabolites to differentiate osteoporosis. RESULTS: We adjusted the analysis for possible confounders (age, BMI, diabetes, smoking, physical activity, vitamin D level, and sex). Valine, leucine, isoleucine, and alanine in women and tryptophan in men were the most important amino acids inversely associated with osteoporosis (OR range from 0.77 to 0.89). Sarcosine, followed by tyrosine, asparagine, alpha aminobutyric acid, and ADMA in women and glutamine in men and when both women and men were considered together were the most discriminating amino acids detected in individuals with osteoporosis (OR range from 1.15 to 1.31). CONCLUSION: We found several amino acid metabolites associated with possible bone status in elderly individuals. Further studies are required to evaluate the utility of these metabolites as clinical biomarkers for osteoporosis prediction and their effect on bone health as dietary supplements.

Nutrition and Diet Therapy in Diabetes Mellitus: A Roadmap based on available evidence.

BACKGROUND: Nutrition is considered as a primary approach for diabetes management. It needs a comprehensive assessment of evidence to identify nutritional dimensions that should be explored in the future. We aimed to provide a roadmap on diabetes and nutrition and clarify research gaps in this field. METHODS: In the present review, we searched Scopus and PubMed electronic databases to collect eligible publications with English and Farsi languages from 2015 to December 2019 in the field of nutrition and diabetes. Relevant papers were classified into six subgroups including biochemistry/ animal studies, clinical nutrition, food industry, genetic, public health, and dietary supplements. Based on evidence-based pyramid, publications were categorized as well. Publications trend from 2015 to 2019 and frequency of publications in each category were provided. RESULTS: Finally, we reached 438 eligible papers. Most studies (40.86%) were clinical trials and in most human studies (n = 224) patients with type 2 diabetes were considered. Probiotic/prebiotic/ symbiotic, vitamin D, and omega-3/fish oil were the most frequent studied dietary supplements. Low portions of studies were dedicated to diabetic children (n = 3), type 1 diabetes (n = 6), diabetes complications (n = 23) and GDM (n = 25). CONCLUSION: An increasing trend in nutrition publications in the field of diabetes was observed. Publications were mostly dedicated to clinical trials with a focus on dietary supplements. Low portion of studies have been dedicated to children with diabetes, diabetes complications, and GDM. More attention to high quality basic research, product-based projects, and interdisciplinary studies in the field of nutrition and diabetes are needed.

Depinar, a drug that potentially inhibits the binding and entry of COVID-19 into host cells based on computer-aided studies.

BACKGROUND AND PURPOSE: The new coronavirus (Covid-19) has resulted in great global concerns. Due to the mortality of this virus, scientists from all over the world have been trying to employ different strategies to tackle down this concern. This virus enters cells via phagocytosis through binding to the angiotensin-converting enzyme II receptor. After invading the body, it can stay hidden in there for a period of up to 24 days (incubation period). EXPERIMENTAL APPROACH: In this report, by the use of in silico studies we selected several FDA-approved compounds that possess antiviral properties. We chose the viral Spike protein as the target of drug compounds and carried out the screening process for the FDA databank in order to find the most effective ligand. FINDINGS/RESULTS: The results from dock and MD revealed 10 compounds with high affinity to the receptor-binding domain motif of S protein. The best inhibitors were the ingredients of Depinar, which managed to effectively block the interactions between cells and virus. CONCLUSION AND IMPLICATION: The results of this study were approved by in silico studies and due to the lack of time; we did not test the efficiency of these compounds through in vitro and in vivo studies. However, the selected compounds are all FDA approved and some are supplements like vitamin B12 and don't cause any side effects for patients.

Mass spectrometry with derivatization method for concurrent measurement of amino acids and acylcarnitines in plasma of diabetic type 2 patients with diabetic nephropathy.

BACKGROUND: Amino acids (AAs) and acylcarnitines play a key role in metabolic disease and can be used as biomarkers of various diseases such as malignancies, type 2 diabetes (T2D), insulin resistance, and cardiovascular diseases, therefore, designing an accurate and simple laboratory method that simultaneously measure both groups of substances, could improve the process of analytes quantification. In this research, a flow injection tandem mass spectrometry (FI-MS/MS) method for simultaneous measurement of AAs and acylcarnitines in addition to results of validation is explained. METHODS: Samples were mixed with internal standards and after derivatization (with butanolic-HCL), AAs, and acylcarnitines were quantified by tandem mass spectrometry (SCIEX API 3200). Analytical performance studies were designed based on the Clinical and Laboratory Standards Institute (CLSI) guidelines including precision, accuracy, linearity, and limit of detection-quantification (LOD-LOQ) experiments. Samples from patients with T2D in different stages of kidney disease were also analyzed to ensure the clinical usage of the method. RESULTS: Performance evaluation of the method demonstrated adequate results. The mean of estimated inter-assay precision (reported as a coefficient variation) for AAs and acylcarnitines were less than 8.7% and 12.3%, the estimated mean bias was below 8.8% and 10.2% respectively. LOD of analytes ranged between 0.6-10 µmol per liter (µmol/L) for AAs and 0.02-1 µmol/L for acylcarnitines. LOQ analytes showed a range of 2-25 µmol/L and 0.05-5 µmol/L for AAs and carnitine/acylcarnitines respectively. In diabetic patients sample analysis, a significant increase in acylcarnitines (C2, C4, C5DC, C6, C8, C10, C14) and citrulline with a significant decrease in valine were seen in patients with severely increased albuminuria. CONCLUSION: FI-MS/MS method with pre-injection derivatization with butanolic-HCL can be used for concurrent measurement of AAs and carnitine/acylcarnitines in a short time and it satisfies the analytical performance requirements. This method is applied for AAs and carnitine/acylcarnitines measurement in patient with T2DM and results show some of the acylcarnitines and AAs can be involved in diabetic nephropathy development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00786-3.

Association of circulating omega 3, 6 and 9 fatty acids with gestational diabetes mellitus: a systematic review.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with increased risks of disease for mother and child during pregnancy and after that. Early diagnosis of GDM would promote both maternal and fetal health. Metabolomics can simplify and develop our understanding of the etiology, manifestation, or pathophysiology of the disease. This systematic review investigates the association of circulating omega 3, 6, and 9 fatty acids with GDM. METHODS: We conducted a systematic search of PubMed, Scopus, Web of Science, and EMBASE databases up to May 8, 2020, using the key term combinations of all types of omega fatty acids with gestational diabetes mellitus. Additional articles were identified through searching the reference lists of included studies. RESULTS: This systematic review included 15 articles. Five were cohort studies, four included nested case-control studies and four were case-control studies. The results of this study demonstrate an increasing trend in the amount of oleic acid and palmitoleic acid in the second trimester and an increase in decosahexanoic acid in the third trimester of GDM mothers. The changes in other fatty acids of interest are either not significant or if significant, their results are inconsistent with the other existing articles. CONCLUSIONS: Omega fatty acids, as potential biomarkers, are considered to be associated with GDM risk and thus provide useful information regarding the prevention and early diagnosis of GDM. Moreover, existing metabolomic studies on GDM are shown to provide conflicting results about metabolite profile characteristics. This systematic review was registered at PROSPERO ( www.crd.york.ac.uk/PROSPERO ) as CRD42020196122.

Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study.

Chronic low-grade inflammation is the hallmark of type 2 diabetes (T2D). Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects, clinical trials addressing these effects in patients with T2D are limited. Therefore, in the present study, we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a randomized, double-blind, placebo-controlled clinical trial. A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks. Percentage of CD14+CD16+ monocytes, plasma levels of inflammatory cytokines (tumor necrosis factor α, interleukin [IL] 1ß, IL-6, and monocyte chemoattractant protein-1), the expression levels of genes involved in the inflammatory responses (toll-like receptor 2, toll-like receptor 4, and nuclear factor κB), lipopolysaccharide-stimulated cytokine (tumor necrosis factor α, IL-1ß, and IL-6) secretion from peripheral blood mononuclear cells, and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study. Compared with the placebo group, we could not detect any significant difference in the percentage of CD14+CD16+ monocytes, lipopolysaccharide-induced cytokine secretion, plasma levels of inflammatory cytokines, and the expression of inflammatory genes in resveratrol group. Moreover, we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure. In conclusion, 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers.

Effect of calcitriol supplementation and tail suspension on serum biomarkers of bone formation in rats.

BACKGROUND: Calcitriol is documented to cause significant increase in bone mass densitometry counteracting osteoporosis. Promising results of calcitriol supplementation in studies aiming space flight induced osteoporosis is little and the effect of this hormone on biomarkers of bone metabolism is not examined yet in space flight models of osteoporosis in rats. METHODS: This was an interventional animal study being performed in a 1-month period. We included 21 Sprague Dawley strain rats (>200 gr, >6 week) who were randomly assigned to receive daily supplementation of oral 0.03µgr calcitriol and to be submitted to tail suspension model. Rats were followed for 1 month and were tested for serum osteocalcin (OC), alkaline phosphatase (ALP) and serum calcium at the beginning and the end of the study period. The results were analyzed and compared between groups. RESULTS: Although serum levels of osteocalcin and alkaline phosphatase biomarkers and total serum calcium were not significantly different within and between study groups, their levels were increased in tail suspension model compared to control group. The levels of these biomarkers were lower in those who were submitted to tail suspension model and received calcitriol supplementation compared to those who were only submitted to tail suspension (60.14 ± 11.73 ng/mL vs. 58.29 ± 2.69 ng/mL; p = 0.696 for osteocalcin and 381.86 ± 99.16 mU/mL vs. 362.57 ± 27.41 ng/mL; p = 0.635 for alkaline phosphatase). CONCLUSION: Supplementation of daily diet with calcitriol in rats under weightlessness conditions may results in lower values for bone metabolic biomarkers of alkaline phosphatase and osteocalcin and serum calcium. This pattern of change in biomarkers of bone formation, may point to the capacity of calcitriol supplementation in preventing cellular process of osteoporosis. Thus calcitriol supplementation could be an available, economic and effective strategy for preventing bone metabolic changes related to weightlessness commonly encountered in space flight. The outcome of this study needs to be further studied in future trying to find more definite results.

Effect of folic acid on bone metabolism: a randomized double blind clinical trial in postmenopausal osteoporotic women.

BACKGROUND: In spite of several studies, the impact of homocysteine level and folic acid supplementation on bone metabolism is yet to be recognized. In this registered clinical trial (IRCT2014042217385N1), we aimed to find out the power of 6-month folic acid supplementation on homocysteine level and bone metabolism. METHODS: Forty postmenopausal osteoporotic women (50 to 87 years) were enrolled in the study. All participants were randomized to receive folic acid 1 mg (n = 17) or placebo (n = 14). At baseline, 3 months, and finally 6 months post intervention, the level of homocysteine, vitamin B12, and bone biomarkers were measured. RESULTS: Both groups were similar at baseline. The homocysteine decreased in both groups but statistically non-significant (P > 0.05). The changes of the serum level of vitamin B12, osteocalcin, and ß cross laps were significant between groups after 6 months (P ≤ 0.05). CONCLUSION: The trend of changes of bone biomarkers after 6 months folic acid supplementation shows that homocysteine concentration and/or folic acid supplementation have impact on the rate of bone metabolism. However, further investigations by larger sample size and differentiating age and gender are still needed to clarify the exact role of folate, homocysteine and vitamin B12.