Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 21, Issue 5, 2021

The current treatment and prevention procedures of oral disorders follow a very targeted approach considering mouth and its structures as a system that is completely independent, than the rest of the body. The main therapeutic approach is to keep the levels of oral bacteria and hygiene in an acceptable range compatible with oral-mouth health, completely separated from systemic microbial homeostasis (eubiosis vs dysbiosis). This can negatively impact the diagnosis of a more complex systemic disease and its progression. Dysbiosis occurs as a consequence of imbalance in oral and gut microbiota which leads to cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, and Alzheimer’s disease, as reported in current literature. Likewise, there is a need to highlight and develop a novel philosophical approach in the treatments for oral diseases that will necessarily involve nonconventional approaches.

Background: Cell death is a fundamental biological phenomenon that contributes to the pathogenesis of various diseases. Regulation of iron and iron metabolism has received considerable research interests especially concerning the progression of metabolic diseases. Discussion: Emerging evidence shows that ferroptosis, a non-apoptotic programmed cell death induced by iron-dependent lipid peroxidation, contributes to the development of complex diseases such as non-alcoholic steatohepatitis, cardiomyopathy, renal ischemia-reperfusion, and neurodegenerative diseases. Therefore, inhibiting ferroptosis can improve the pathophysiology of associated metabolic diseases. This review describes the vital role of ferroptosis in mediating the development of certain metabolic diseases. Besides, the potential risk of iron and ferroptosis in atherosclerosis and cardiovascular diseases is also described. Iron overload and ferroptosis are potential secondary causes of death in metabolic diseases. Moreover, this review also provides potential novel approaches against ferroptosis based on recent research advances. Conclusion: Several controversies exist concerning mechanisms underlying ferroptotic cell death in metabolic diseases, particularly in atherosclerosis. Since ferroptosis participates in the progression of metabolic diseases such as non-alcoholic steatohepatitis (NASH), there is a need to develop new drugs targeting ferroptosis to alleviate such diseases.

Aim: Investigating about the history of allergies and discovery of the histamine’s role in the immune response through historical references, starting with ancient anecdotes, analysing the first immunization attempts on animals to understand its importance as the anaphylaxis mediator. Moreover, we shortly resume the most recent discoveries on mast cell role in allergic diseases throughout the latest updates on its antibody-independent receptors. Methods: Publications, including reviews, treatment guidelines, historical and medical books, on the topic of interest were found on Medline, PubMed, Web of Knowledge, Web of Science, Google Scholar, Elsevier’s (EMBASE.comvarious internet museum archives. Texts from the National Library of Greece (Stavros Niarchos Foundation), from the School of Health Sciences of the National and Kapodistrian University of Athens (Greece). We selected key articles which could provide ahistorical and scientific insight into histamine molecule and its mechanism of action’s discovery starting with Egyptian, Greek and Chinese antiquity to end with the more recent pharmacological and molecular discoveries. Results: Allergic diseases were described by medicine since ancient times, without exactly understanding the physio-pathologic mechanisms of immuno-mediated reactions and of their most important biochemical mediator, histamine. Researches on histamine and allergic mechanisms started at the beginning of the 20th century with the first experimental observations on animals of anaphylactic reactions. Histamine was then identified as their major mediator of many allergic diseases and anaphylaxis, but also of several physiologic body’s functions, and its four receptors were characterized. Modern researches focus their attention on the fundamental role of the antibody-independent receptors of mast cells in allergic mechanisms, such as MRGPRX2, ADGRE2 and IL-33 receptor. Conclusion: New research should investigate how to modulate immunity cells activity in order to better investigate possible multi-target therapies for host’s benefits in preclinical and clinical studies on allergic diseases in which mast cells play a major role.

Cardiovascular diseases are the leading cause of death in the modern world and dyslipidemia is one of the major risk factors. The current therapeutic strategies for cardiovascular diseases involve the management of risk factors, especially dyslipidemia and hypertension. Recently, the updated guidelines of dyslipidemia management were presented, and the newest data were included in terms of diagnosis, imaging, and treatment. In this targeted literature review, the researchers presented the most recent evidence on dyslipidemia management by including the current therapeutic goals for it. In addition, the novel diagnostic tools based on theranostics are shown. Finally, the future perspectives on treatment based on novel drug delivery systems and their potential to be used in clinical trials were also analyzed. It should be noted that dyslipidemia management can be achieved by the strict lifestyle change, i.e., by adopting a healthy life, and choosing the most suitable medication. This review can help medical professionals as well as specialists of other sciences to update their knowledge on dyslipidemia management, which can lead to better therapeutic outcomes and newer drug developments.

Diabetic nephropathy (DN) is referred to as the microvascular complication of the kidneys induced by insufficient production of insulin or an ineffective cellular response to insulin, and is the main cause of end-stage renal disease. Currently, available therapies provide only symptomatic relief and fail to improve the outcome of diabetic nephropathy. Studies on diabetic animals had shown overexpression of SIRT1 in both podocytes and renal tubular cells attenuated proteinuria and kidney injury in the animal model of DN. Sirt1 exerts renoprotective effects in DKD in part through the deacetylation of transcription factors involved in the disease pathogenesis, such as NF-B, Smad3, FOXO and p53. The purpose of this review is to highlight the protective mechanism of SIRT1 involved in the pathogenesis of diabetic nephropathy.

Apart from their main function as oxygen carriers in vertebrates, erythrocytes are also involved in immune regulation. By circulating throughout the body, the erythrocytes are exposed and interact with tissues that are damaged as a result of a disease. In this study, we summarize the literature regarding the contribution of erythrocytes to immune regulation and metabolism. Under the circumstances of a disease state, the erythrocytes may lose their antioxidant capacity and release Damage Associated Molecular Patterns, resulting in the regulation of innate and adaptive immunity. In addition, the erythrocytes scavenge and affect the levels of chemokines, circulating cell-free mtDNA, and C3b attached immune complexes. Furthermore, through surface molecules, erythrocytes control the function of T lymphocytes, macrophages, and dendritic cells. Through an array of enzymes, red blood cells contribute to the pool of blood’s bioactive lipids. Finally, the erythrocytes contribute to reverse cholesterol transport through various mechanisms. Our study is highlighting overlooked molecular interactions between erythrocytes and immunity and metabolism, which could lead to the discovery of potent therapeutic targets for immunometabolic diseases.

Background: Practitioners of traditional medicine use the decoction of Ononis natrix L. to treat hyperglycemia. The literature offers no evidence to support the use. Objective: To investigate the effect of the decoction of Ononis natrix L. on the blood glucose concentration in Wistar rats (Rattus norvegicus) with streptozotocin-induced diabetes mellitus. Methods: We obtained 35 Wistar rats from the animal colony of The University of Jordan School of Medicine. We induced diabetes by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and 23 rats (66%) survived to allocation. We randomly assigned the rats to one of four groups: negative control (1% Tween 80 in distilled water), positive control (100 mg/kg metformin), high-dose treatment (7.5 mL of the decoction), and low-dose treatment (3.5 mL of the decoction). We administered the doses twice daily by oral gavage for two weeks and measured the tailblood glucose concentration twice daily, once before the first dose and another time after the second dose. We used linear mixed-effects regression to model the change in blood glucose concentration as a function of the experimentation groups, with adjustments for pseudoreplication and temporal variation. Results: The estimated mean change was 1 mmol/L (−30 to 31 mmol/L) for the negative control group, −26 mmol/L (−56 to 5 mmol/L) for the positive control group, −75 mmol/L (−108 to −42) for the low-dose treatment group, and −82 mmol/L (−111 to −53 mmol/L) for the high-dose treatment group. Conclusion: In conclusion, we demonstrate, for the first time, the hypoglycemic effect of Ononis natrix L. in an animal model of diabetes.

Background and Objective: Studies on the relationship of thyroid stimulating hormone (TSH) within the reference range and thyroid autoimmunity with osteoporosis have produced conflicting results. The objective of this study was to investigate the association of thyroid function and thyroid autoimmune bodies (TPOAb and TgAb) with osteoporosis in euthyroid postmenopausal women. Methods: A total of 174 subjects were retrospectively included. Serum TSH, total T3, total T4, TPOAb, TgAb, vitamin D, calcium and bone mineral density were measured. Correlation and logistic multivariate regression analysis were performed. Results: Levels of TSH were lower in osteoporosis group (TSH: 2.03±1.08 vs 2.40±1.24 mIU/L, p=0.040) while TT3 and TT4 levels were similar between the two groups. The positive percentage of anti-TPO antibodies was higher in osteoporosis group (17.9% vs 6.7%, χ²= 5.13, p=0.024) while no significant difference was observed for anti-Tg antibodies (17.9% vs 8.9%, χ²=3.05, p=0.081). The Spearman correlation analysis showed that TSH levels were significantly correlated with lumbar spine BMD (r= 0.161, P=0.035) and femoral neck BMD (r = 0.152, P= 0.045). Logistical regression analysis revealed that low-normal TSH levels and positive TPOAb was an independent risk factor for osteoporosis (OR: 0.698, 95% CI: 0.505-0.965, p=0.030; OR: 3.961, 95% CI: 1.176-13.345, p=0.026 respectively). Conclusion: The results showed that low-normal TSH levels and anti-TPO antibodies were independently associated with the presence of osteoporosis in postmenopausal women.

Background: Reducing the healing time of wounds can decrease the patient's immobility time and their medical costs, leading a faster return of the patients to daily work. Objective: The aim of the present study is to compare the effect of adipose-derived stem cells and curcumin- containing liposomal nanoparticles with phenytoin on wound healing. Methods: After anesthesia of the rats, open skin ulcers were made by a bistoury blade. Subsequently, stem cells were removed from the adipose tissue of the upper border of the epididymis. The originality of stem cells was then confirmed by the flow cytometry. The fusion method was used to prepare the liposome; and also, nanoliposomal particles were confirmed by using the DLS microscope. The percentage of recovery and the cell count was measured with IMAGEJ. The expression of genes was assessed by PCR. The number of fibroblasts was counted by immunohistochemistry techniques. The amount of collagen was determined by Tri-chromosome staining, and the number of capillaries was enumerated by H & E staining. Results: The expression of the TGF-β1 gene, vascular number, wound healing rate and the number of fibroblasts increased significantly in adipose tissue-derived stem cells and curcumin nanoliposome groups (p<0.05); the wound surface was also decreased significantly (p<0.05). Conclusion: Based on the results of our research, adipose tissue-derived stem cells and curcumin nanoliposomes can heal wounds efficiently.

Aim: In this study, we aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. Methods: Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3 were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured. Results: Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 μmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 μmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal. Conclusion: T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3 supplementation.

Aim: This study aimed to investigate the effect of Micromeria graeca on blood glucose levels and lipid parameters in an experimental model of diabetes. Background: Micromeria graeca (L.) Benth. ex Rchb is a medicinal plant used in Morocco for the treatment of several pathologies including diabetes. Objective: This study aimed to evaluate the antihyperglycemic and antihyperlipidemic effects of the aqueous extract of Micromeria graeca (M. graeca) aerial parts (AEMG) under physiological (normal rats) and pathological (STZ-induced diabetic rats) conditions. Additionally, we analyzed the phytochemical composition and antioxidant capacity. Methods: The effects of the acute and sub-chronic administration of AEMG (20 mg/kg) on blood glucose levels and lipid profiles were evaluated in normal and streptozotocin-induced diabetic rats. Moreover, the phytochemical analysis was carried with standard tests and estimation of total phenolics compounds by Folin–Ciocalteu reagent. The antioxidant activity was realized by the DPPH method. Results: Single oral administration of M. graeca aqueous extract decreased blood glucose levels 4 and 6 hours (p<0.01) after treatment in diabetic rats. In accordance, the repeated oral administration of M. graeca showed a significant reduction in blood glucose levels in diabetic rats since the second day to the end of the period experiment (p<0.0001). In addition, two weeks of treatment with M. graeca reduced total cholesterol levels (p<0.05) with a significant increase of HDL-c level (p<0.01) in diabetic rats. Moreover, M. graeca scavenged DPPH radical in a dose-dependent manner (IC50=0.48 mg/ml), whereas IC50 was 0.55 mg/ml for BHT. Phytochemical analysis showed the richness of Micromeria graeca on polyphenols (281.94±4.61 mg GAE/1 g), flavonoids, tannins, glycosides, saponins, sterols, sesquiterpenes, and terpenoids. Conclusion: AEMG exhibits antihyperglycemic and antihyperlipidemic activities in STZ-induced diabetic rats and a potent antioxidant capacity.

Aims: This study aimed to evaluate the antidiabetic and antihyperlipidemic effects of Asteriscus graveolens. Background: Asteriscus graveolens (Asteraceae) is a medicinal plant widely used by the Moroccan population to treat various diseases, including diabetes. Objective: This work aimed to assess the capacity of flavonoids extracted from Asteriscus graveolens (FEE) to improve diabetes mellitus and dyslipidemia in normal and STZ-induced diabetic rats. Methods: Flavonoids were extracted from A. graveolens using the Soxhlet apparatus and using different organic solvents. Normal and streptozotocin-induced diabetic rats were treated orally by the extract of A. graveolens at a dose of 10 mg/kg. The oral treatment during 15 days was used to evaluate the effect of the flavonoids extracted from A. graveolens on blood glucose level and lipid profile in normal and diabetic rats. The oral glucose tolerance test, as well as the analysis of the histopathological examination of the liver, was performed. The antioxidant activity of FEE was also assessed by the method of trapping of free radical 2,2-diphenyl-1 picrylhydrazyl (DPPH), in order to estimate the mechanisms of action involved by FEE to improve hyperglycemia and lipid profile in normal and diabetic rats. Results: FEE reduced serum glucose concentrations in both normal and diabetic rats and exhibited lowering total cholesterol and triglycerides effects as well as improvement of the HDL-cholesterol serum level in the last group. In addition, a remarkable influence on glucose tolerance was also noticed after FEE treatment. Moreover, FEE was able to improve the histopathological status of the liver and was found to possess a potent antioxidant effect in vitro. Conclusion: In conclusion, this study demonstrates the hypoglycemic and antihyperlipidemic effects of FEE in rats and supports its traditional use for the management of diabetes.

Objective: 1,3,4-thiadiazole (A), 1,3,4-oxadiazole (B) and 1,2,4-triazole (C) derivatives have been known for their immense pharmacotherapeutic potential. The current research article attempts to further explore and understand the probable biochemical mechanism related to antiinflammatory activity of derivatives. Methods: The screened A, B and C derivatives were investigated for both in-vitro (Erythrocyte Membrane stabilization activity, Proteinase enzyme inhibitory activities) and in-vivo correlation using acute and chronic anti-inflammatory potential by carrageenan induced rats paw edema and cotton pellet granuloma methods, respectively. The activity was studied after interpreting acute toxicity studies results. Results: In vitro studies in the case of Erythrocyte Membrane stability and Proteinase enzyme inhibitory activities exhibited by A, B, and C at 100 ppm were found to be 48.89%, 51.08% and 50.08% and 66.78%, 76.91% and 57.41%, respectively. The maximum toxic dose was found to be 2000 mg/kg. The derivatives were studied for two-dose levels viz; Lower (100 mg/kg) and higher dose (200 mg/kg). In rat paw edema, maximum decrease was obtained for A (50.05%), B (50.05%) and C (51.06%) at lower and higher dose at 68.76%, 55.61%, and 65.26%, respectively for effect up to 24 h. In the chronic model of cotton pellet granuloma viz; higher and lower doses of A, B and C exhibited 38.15%, 33.19% and 30.25 % and 19.45%, 18.55% and 17.55 %, respectively. Conclusion: The studied models depicted that derivatives A, B and C have the probable potential as anti-inflammatory agents. Further studies need to be undertaken to explore their potential in the different therapeutic areas.

Background: Elevated human epididymis secretory protein 4 (HE4) serum levels have been widely investigated in patients with ovarian cancer. However, high levels of HE4 can be also found in other tumors and in renal fibrosis. To date, the HE4 assay manufacturer features the reference value only for the female pre- and post-menopausal population. The aim of this study was to determine the upper reference limit (URL) of HE4 in a well-defined and large cohort of healthy male individuals and investigate potential factors influencing HE4 levels in healthy subjects. Methods: The study included 307 Italian healthy male individuals. HE4 was measured using a chemiluminescent assay (Abbott Laboratories, Wiesbaden, Germany). The URL was calculated using the non-parametric percentile method. Differences in HE4 concentrations according to age, estimated glomerular filtration rate (eGFR), free and bioavailable testosterone were also evaluated. Results: The 97.5th percentile URL of serum HE4 in our study population was 57 pmol/L (90% CI). After stratifying subjects according to age, we found that the URL of HE4 was higher in older (> 50 years) than in younger subjects (18-30 years old), and overlapping with the URL in males from 31 to 50 years old (P=4.769e-16, r=0.44). A strong negative correlation between HE4 and eGFR was observed (P=8.412e-12, r=-0.38). Moreover, a statistically significant negative correlation was also found between HE4 and free and bioavailable testosterone. Conclusion: This study determined the URL of HE4 in a large cohort of healthy male subjects. Our findings indicate that the HE4 age-dependent differences in males need to be taken into account. The definition of the HE4 URL in males and the correlation observed with eGFR and testosterone should foster the clinical use of HE4 beyond gynecologic cancer.

Objective: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemic agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, therefore, this combination required careful administration for patients. In the present study, the effects of combination therapy of pemafibrate, a novel fibrate, and statins, was evaluated. Methods: Pemafibrate was administered for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group was examined. Results: In the combination group, a decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with an increase in HDL-cholesterol. While serum triglyceride level was reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, a decrease in γ-glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group. Conclusion: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

Background: Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. Objective: We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. Methods: We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. Results: AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF- 173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon 54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). Conclusion: As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.

Objective: The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. Methods: PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. Results: Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference. Conclusion: Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

Background: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and the risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS.

Methods: All accessible studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models.

Results: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS.

Conclusion: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in the prevention or treatment of the MetS.

Aim: This study was designed to make a systematic review and meta-analysis on randomized controlled trials (RCTs) assessing the effect of cinnamon on blood pressure (BP). Methods: A systematic computerized literature search of PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar databases was conducted up to August 2019. All RCTs using cinnamon supplements in adults were included in this systematic review and meta-analysis. Results: Out of 927 records, 8 trials that enrolled 582 participants were included. The pooled effect size showed that SBP did not change following cinnamon supplementation. (WMD: -0.61mmHg; 95% CI: -1.36, 0.14, P= 0.111). Also cinnamon supplementation in long-duration (≥ 8weeks) had a significant effect on SBP (WMD: -1.25 mmHg; 95% CI: -2.22, -0.28, P= 0.012). Pooled analysis showed that cinnamon had a significant effect on DBP (WMD: -0.93mmHg, 95% CI: -1.55 to -0.32, P= 0.003). In addition, results from both duration subsets and high dose (>1500 mg/day) of cinnamon supplementation were significant. Conclusion: Our findings revealed that cinnamon supplementation has favorable effects on DBP although results of SBP were not the same. Nonetheless, further studies are required.

Background and Aim: Although it is widely known that the total parenteral nutrition (TPN) used frequently in intensive care units has unwanted side effects, there is little known about how it interferes with the amino acid levels taken during the diagnosis of metabolic diseases. Amino acid can lead to inaccurate measurements with mass spectrometry due to its high molecular content of lipids and carbohydrates, which modifies the blood matrix. The purpose of this study was to emphasize the results of amino acid interference, measured with mass spectrometry, in patients administered with TPN. Case Presentation: Incorrect clinical interpretation resulted in the case of a pneumonia patient with false positive and negative blood amino acid levels caused by TPN infusion. The amino acid profile had been requested to rule out an amino acid metabolic defect in the two-year-old boy who arrived at the pediatric clinic complaining of respiratory distress, tachypnea and hypoxemia. He was monitored in the intensive care unit for further investigation. The personnel who had performed phlebotomy also carried out the sampling during the TPN infusion administration. This caused the amino acid results and an incorrect interpretation. The following deviation ratios were detected: phenylalanine 102%, leucine 86%, isoleucine 106%, GABA 200%, citrulline 238%, glutamine 178%, ornithine 216%, 1- methyl-l-histidine 1471%, serine 312%, alanine 163%, glycine 355%, homocitrulline and carnosine 444%. The amino acid blood level measurements taken for diagnosis and screening in suspected metabolic disease may lead to involuntary false low or elevated results in patients administered with TPN. Conclusion: This case demonstrates that TPN solutions affect the reference method of mass spectrometry measurement methods due to the concentration of ingredients. We suggest that inaccurate results can be avoided by carrying out the sampling prior to TPN infusion in patients whose plasma amino acid levels will be measured.