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.

Circulating amino acids and acylcarnitines correlated with different CAC score ranges in diabetic postmenopausal women using LC-MS/MS based metabolomics approach.

BACKGROUND: Diabetes mellitus (DM) and its cardiovascular disease (CVD) complication are among the most frequent causes of death worldwide. However, the metabolites linking up diabetes and CVD are less understood. In this study, we aimed to evaluate serum acylcarnitines and amino acids in postmenopausal women suffering from diabetes with different severity of CVD and compared them with healthy controls. METHODS: Through a cross-sectional study, samples were collected from postmenopausal women without diabetes and CVD as controls (n = 20), patients with diabetes and without CVD (n = 16), diabetes with low risk of CVD (n = 11), and diabetes with a high risk of CVD (n = 21) referred for CT angiography for any reason. Metabolites were detected by a targeted approach using LC-MS/MS and metabolic -alterations were assessed by applying multivariate statistical analysis. The diagnostic ability of discovered metabolites based on multivariate statistical analysis was evaluated by ROC curve analysis. RESULTS: The study included women aged from 50-80 years with 5-30 years of menopause. The relative concentration of C14:1, C14:2, C16:1, C18:1, and C18:2OH acylcarnitines decreased and C18 acylcarnitine and serine increased in diabetic patients compared to control. Besides, C16:1 and C18:2OH acylcarnitines increased in high-risk CVD diabetic patients compared to no CVD risk diabetic patients. CONCLUSION: Dysregulation of serum acylcarnitines and amino acids profile correlated with different CAC score ranges in diabetic postmenopausal women. (Ethic approval No: IR.TUMS.EMRI.REC.1399.062).

Metabolic signatures of insulin resistance in non-diabetic individuals.

BACKGROUND: Insulin resistance (IR) evolved from excessive energy intake and poor energy expenditure, affecting the patient's quality of life. Amino acid and acylcarnitine metabolomic profiles have identified consistent patterns associated with metabolic disease and insulin sensitivity. Here, we have measured a wide array of metabolites (30 acylcarnitines and 20 amino acids) with the MS/MS and investigated the association of metabolic profile with insulin resistance. METHODS: The study population (n = 403) was randomly chosen from non-diabetic participants of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS 2016). STEPS 2016 is a population-based cross-sectional study conducted periodically on adults aged 18-75 years in 30 provinces of Iran. Participants were divided into two groups according to the optimal cut-off point determined by the Youden index of HOMA-IR for the diagnosis of metabolic syndrome. Associations were investigated using regression models adjusted for age, sex, and body mass index (BMI). RESULTS: People with high IR were significantly younger, and had higher education level, BMI, waist circumference, FPG, HbA1c, ALT, triglyceride, cholesterol, non-HDL cholesterol, uric acid, and a lower HDL-C level. We observed a strong positive association of serum BCAA (valine and leucine), AAA (tyrosine, tryptophan, and phenylalanine), alanine, and C0 (free carnitine) with IR (HOMA-IR); while C18:1 (oleoyl L-carnitine) was inversely correlated with IR. CONCLUSIONS: In the present study, we identified specific metabolites linked to HOMA-IR that improved IR prediction. In summary, our study adds more evidence that a particular metabolomic profile perturbation is associated with metabolic disease and reemphasizes the significance of understanding the biochemistry and physiology which lead to these associations.

Iranian Multi-center Osteoporosis Study (IMOS), 2021-2022: the study protocol.

BACKGROUND: This paper presents the protocol of the 4th round of Iranian Multi-center Osteoporosis Study (IMOS), a national survey with the primary objective of estimating the prevalence of osteoporosis and sarcopenia and their risk factors in a representative sample of urban and rural populations. METHODS: The target population of the survey is all individuals ≥ 50 years in Iran. A multi-stage random sampling method has been used in the study. We stratified the 31 provinces of the country into 5 strata based on the distribution of their potential risk factors for osteoporosis and randomly selected one or two provinces from each stratum. Then, we invited 2530 people aged ≥ 50 years recruited in the 8th National Survey of None Communicable Diseases (NCD) Risk Factors (STEPs-2021) in the selected provinces to participate in IMOS. Body composition measurements including bone mineral density, muscle mass, and fat mass are measured through Dual-energy X-ray Absorptiometry (DXA) method using HOLOGIC (Discovery and Horizon) devices; and Trabecular Bone Score (TBS) is measured on the DXA scans using iNsight software. Anthropometric measurement and physical examinations are made by a trained nurses and other required information are collected through face-to-face interviews made by trained nurses. Laboratory measurements are made in a central lab. The prevalence of osteoporosis and sarcopenia will be estimated after applying sampling design, non-response, and post-stratification weights to the data. DISCUSSION: IMOS will provide valuable information on the prevalence and determinants of osteoporosis and sarcopenia at the national level, and the results can be used in evaluating health system interventions and policymaking in the field of musculoskeletal diseases.

WT1 and ACE mRNAs of blood extracellular vesicle as biomarkers of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN. METHODS: The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs. RESULTS: DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = - 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively. CONCLUSIONS: WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.

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.

Association between biomarkers of bone health and osteosarcopenia among Iranian older people: The Bushehr Elderly Health (BEH) program.

BACKGROUND: Osteosarcopenia is referred to as co-incidence of osteoporosis/osteopenia and sarcopenia which is defined as a geriatric syndrome with a significant prevalence that increases morbidity and mortality. There are some relevant factors that can show an increased risk of incidence of osteosarcopenia. AIM: We aimed to consider the association of bone turnover markers such as Osteocalcin (OC), C-terminal cross-linked telopeptide (CTX), Tartrate Resistant acid Phosphatase (TRAP), Bone Alkaline Phosphatase (BALP) and also other factors like vitamin D, calcium, phosphorous, and ALP with osteosarcopenia in elderly. METHODS: We carried out a cross-sectional study on a random sample including 400 elder participants of Bushehr Elderly Health (BEH) study, in Iran. Osteopenia/ osteoporosis was defined as a T-score ≤ -1.0 standard deviation below the mean values of a young healthy adult. We defined sarcopenia as low muscle strength (handgrip strength<26 kg for men and <18 kg for women) with reduced skeletal muscle mass [Skeletal muscle index (SMI) < 7.0 kg/m2 for male and <5.4 kg/m2 for female]. Osteosarcopenia was considered as the presence of both osteopenia/osteoporosis and sarcopenia. We estimated the age-standardized prevalence of osteosarcopenia for men and women, separately. We used multivariable logistic regression to address the factors associated with osteosarcopenia. RESULTS: The results showed that there was a statistically significant difference in OC), CTX, TRAP were between the osteosarcopenia (-) and osteosarcopenia (+) groups. No statistically significant difference was observed in BALP, vitamin D, calcium, phosphorous, and ALP between the compared groups. In the multivariable logistic regression model, OC and CTX were associated with increased likelihood of osteosarcopenia [adjusted OR= 1.023(1.002-1.045 for OC, 4.363(1.389-15.474 for CTX)]. Furthermore, TRAP increases the odds of osteosarcopenia in crude model [OR= 1.333 (1.070- 1.660)]. CONCLUSIONS: We observed the association between bone turnover markers particularly OC, CTX and osteosarcopenia. Given the rapid growth of the aging population, we should focus on geriatric diseases such as musculoskeletal disorders. Bone turnover markers maybe improve the early diagnosis, screening and assess the response to therapies in people with osteosarcopenia.

Cell Therapy Targets for Autism Spectrum Disorders: Hopes, Challenges and Future Directions.

Autism spectrum disorders as a group of pediatric neurodevelopmental diseases is a crucial part of the worldwide disabilities which have influence in communication skills, social interactions, and ability to understand the concepts. The precise pathophysiology of autism spectrum disorders due to the abundance of involved mechanisms is unknown. Some of these involved mechanisms are related to genetic factors, chronic neuro inflammation, mitochondrial dysfunction, oxidative stress, immune dysregulation, hormonal imbalance, and environmental factors. Current main treatments for autisms are behavioral, nutritional and medical therapies, however there is not definitive treatment approach. Therein, more novel therapies are still required to improve the symptoms. Several preclinical and clinical evidence were shown that stem cell therapy is a potential treatment option for autism spectrum disorders individuals. Considering the significant factors which can affect the outcome of stem cell therapeutic effects including stem cell types, route and dosage of administration, and mechanism of activity along with selecting best animal models can be very important in performing clinical trials.

Stability of Thirty-Four Analytes in Blood Samples of Diabetic Patients.

BACKGROUND: Storage of biological samples may alter the values of an analyte compared to that of initial measurement. Therefore, an optimal storage condition for every analyte in serum and whole blood samples needs to be determined. The aim of this study was to investigate stability of 34 analytes at different time and temperature conditions of storage. METHODS: This study assessed the stability of hematological parameters in whole blood sample and common biochemical analytes in serum of 40 diabetic patients after 24 and 48 hours in 2 - 8°C and after 30 days in -20°C of sample collection. The mean values of analytes in 3 different storage conditions were measured and compared to that of initial values. RESULTS: Most of the examined biochemical analytes and hematological parameters were stable up to 48 hours at 2 - 8°C after sample collection. Most of the negative changes were negligible but PTH level dramatically decreased after 48 hours in 2 - 8°C. In addition, although a clear increase in the concentration of triglycerides, Cr, Urea, T4, and 25-OH vitamin D3 was observed, it was not significant. Furthermore, a statistically significant difference was observed in the values of ALT, Ca, and T4 among the different conditions of storage. Also, values of HbA1c did not show any significant statistical changes among the 3 different conditions of storage. CONCLUSIONS: Taken together, it seems that most of the analytes in the serum of diabetic patients as well as HbA1c are stable up to 30 days of storage.

Insight into blood pressure targets for universal coverage of hypertension services in Iran: the 2017 ACC/AHA versus JNC 8 hypertension guidelines.

BACKGROUND: We compared the prevalence, awareness, treatment, and control of hypertension in Iran based on two hypertension guidelines; the 2017 ACC/AHA -with an aggressive blood pressure target of 130/80 mmHg- and the commonly used JNC8 guideline cut-off of 140/90 mmHg. We shed light on the implications of the 2017 ACC/AHA for population subgroups and high-risk individuals who were eligible for non-pharmacologic and pharmacologic therapies. METHODS: Data was obtained from the Iran national STEPS 2016 study. Participants included 27,738 adults aged ≥25 years as a representative sample of Iranians. Regression models of survey design were used to examine the determinants of prevalence, awareness, treatment, and control of hypertension. RESULTS: The prevalence of hypertension based on JNC8 was 29.9% (95% CI: 29.2-30.6), which soared to 53.7% (52.9-54.4) based on the 2017 ACC/AHA. The percentage of awareness, treatment, and control were 59.2% (58.0-60.3), 80.2% (78.9-81.4), and 39.1% (37.4-40.7) based on JNC8, which dropped to 37.1% (36.2-38.0), 71.3% (69.9-72.7), and 19.6% (18.3-21.0), respectively, by applying the 2017 ACC/AHA. Based on the new guideline, adults aged 25-34 years had the largest increase in prevalence (from 7.3 to 30.7%). They also had the lowest awareness and treatment rate, contrary to the highest control rate (36.5%) between age groups. Compared with JNC8, based on the 2017 ACC/AHA, 24, 15, 17, and 11% more individuals with dyslipidaemia, high triglycerides, diabetes, and cardiovascular disease events, respectively, fell into the hypertensive category. Yet, based on the 2017 ACC/AHA, 68.2% of individuals falling into the hypertensive category were eligible for receiving pharmacologic therapy (versus 95.7% in JNC8). LDL cholesterol< 130 mg/dL, sufficient physical activity (Metabolic Equivalents≥600/week), and Body Mass Index were found to change blood pressure by - 3.56(- 4.38, - 2.74), - 2.04(- 2.58, - 1.50), and 0.48(0.42, 0.53) mmHg, respectively. CONCLUSIONS: Switching from JNC8 to 2017 ACC/AHA sharply increased the prevalence and drastically decreased the awareness, treatment, and control in Iran. Based on the 2017 ACC/AHA, more young adults and those with chronic comorbidities fell into the hypertensive category; these individuals might benefit from earlier interventions such as lifestyle modifications. The low control rate among individuals receiving treatment warrants a critical review of hypertension services.

Association of microRNA gene polymorphisms with Type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder with growing prevalence and increasing economic burden. Based on the role of genetics and epigenetic factors on T2DM, we aimed to carry a systematic review and meta-analysis for all miRNA gene polymorphisms and risk of T2DM. MATERIALS AND METHODS: A computerized literature search was carried out on PubMed, Web of Science, Scopus, Embase, as well as references of relevant review/meta-analysis. Key search terms were "Diabetes Mellitus, Type 2," "MicroRNAs," and "Polymorphism, Single Nucleotide." All types of observational studies from January 1, 1992, to November 30, 2019, were included, without language restriction. Data analysis was performed using R programming language (3.5.2). Level of heterogeneity was obtained by Cochran's Q test (P < 0.05), and subgroup analysis was performed based on ethnicity. RESULTS: Thirty-two polymorphisms from fifteen articles were included. Meta-analysis was carried out based on minor allele frequencies. Seven studies with 2193 cases and 3963 controls were included for rs2910164 polymorphism. In subgroup analysis, there were significant results in Caucasian population in dominant model (odds ratio [OR] =1.12; 95% confidence interval [CI]: 0.83-1.51), homozygote model (OR = 1.78; 95% CI: 1.06-3.00), heterozygote model (OR = 1.77; 95% CI: 1.03-3.05), and recessive model (OR = 1.78; 95% CI: 1.07-2.96). Four studies with 2085 cases and 1933 controls were included for rs895819 polymorphism. Overall, there was no significant result for association with rs895819, but subgroup analysis revealed that minor allele significantly decreased the risk of T2DM in Caucasians by recessive model (OR = 0.34; 95% CI: 0.18-0.66), dominant model (OR = 0.70; 95% CI: 0.52-0.94), homozygote model (OR = 0.32; 95% CI: 0.16-0.62), heterozygote model (OR = 0.37; 95% CI: 0.19-0.74), allelic model (OR = 0.67; 95% CI: 0.52-0.85). CONCLUSION: The minor allele of rs2910164 may increase the risk of T2DM by leading to lower level of miR-146a. In contrast, minor allele of rs895819 may decrease the risk of T2DM by leading to higher level of miR-27a.

Bibliometric analysis of global scientific research on Coronavirus (COVID-19).

Background: Since the outbreak of the novel coronavirus disease from Wuhan, China, in early December 2019, many scientists focused on this infection to find a way to deal with it. Due to the dramatic scientific growth in this field, we conducted a scientometric study to gain a better understanding of the scientific literature on COVID-19. Methods: We extracted all COVID-19 documents indexed in the Scopus from December 1, 2019, to April 1, 2020, without any language limitation and determined their bibliometric characteristics, including document type, open accessibility status, citation counting, H-index, top cited documents, the most productive countries, institutions and journals, international collaboration, the most frequent terms and keywords, journal bibliographic coupling and cocitations. Results: A total of 923 documents on COVID-19 were retrieved, of which 418 were original articles. All documents had received 2551 citations with an average citation of 2.76 per document and an h-index of 23. China ranked first with 348 documents, followed by the United States (n = 160). The Lancet and BMJ Clinical Research Ed published the most documents (each with 74 documents) and 2 institutions (University of Hong Kong and Huazhong University of Science and Technology) ranked first in this regard. In addition, the present study analyzed the top 25 highly-cited documents (those that had received 70% of all citations). Conclusion: This study highlighted the focused subjects on various aspects of COVID-19 literature such as pathogenesis, epidemiology, transmission, diagnosis, treatment, prevention, and its complications.

The Effect of Blood Sample Storage Conditions on HbA1c Concentration.

BACKGROUND: HbA1c concentration is an indicator of the development of long-term complications in diabetic pa-tients. Different sample storage conditions could affect HbA1c values and consequently, clinician's diagnosis. In this study, we studied the effects of various temperatures of storage over time on HbA1c results. METHODS: A total of 40 fresh whole blood samples with various levels of HbA1c were selected for separate HbA1c measurements at three different temperatures (-20°C, 4°C, and 25°C) on subsequent days (0, 7, 14, and 21 days af-ter sample collection) with Cobas Integra 400 assays (Roche Diagnostics, Mannheim Germany). RESULTS: The value of HbA1c at initial measurement (7.05 ± 1.45) was insignificantly higher than results of temper-ature of -20°C and 4° but compared to results at the temperature of 25°C, (6.08% ± 0.86 % after day 7, 5.52% ± 0.80 after day 14, 4.81 % ± 0.66 after day 21) values of initial measurements were significantly higher. CONCLUSIONS: We concluded that the refrigerator or freezer storage temperature is applicable for the measurement of HbA1c by Cobas Integra 400 without adverse effects on the stability of samples on subsequent days.

Decreased Serum Level of miR-155 is Associated with Obesity and its Related Metabolic Traits.

BACKGROUND: Type 2 diabetes is the most common metabolic disease, affecting many of the adult population all around the world. In recent years much attention has been paid to the role of circulating miRNAs as novel biomarkers for various diseases. The aim of this study was to investigate the expression level of miR-155 in serum samples of diabetic and healthy subjects. METHODS: 42 healthy and 45 type 2 diabetic subjects participated in the study. Serum miR-155 level of the subjects was measured using real-time PCR. The levels of IL-6 and TNF-α were quantified using ELISA. RESULTS: There was no significant difference in the level of miR-155 between the diabetic and non-diabetic groups. The level of miR-155 in non-diabetic obese group was significantly lower than the non-diabetic lean subjects. Correlation analyses in non-diabetic group revealed a significant negative correlation between the amount of miR155 and body mass index and cholesterol levels after the elimination of the confounding factors. In diabetic group, a negative correlation was found between miR-155 and insulin, HOMA-IR, and waist circumference levels. Furthermore, no significant relationship between miR-155 and inflammatory cytokines (TNF-α and IL-6) was observed in both diabetic and healthy groups. CONCLUSIONS: A reduced level of miR-155 might associate with obesity and its related metabolic traits such as hyperinsulinemia and dyslipidemia.

Decreased expression of microRNA-21 is associated with increased cytokine production in peripheral blood mononuclear cells (PBMCs) of obese type 2 diabetic and non-diabetic subjects.

The aim of this study was to investigate the role of miR-21 in inflammatory responses in peripheral blood mononuclear cells (PBMCs) of type 2 diabetic (T2D) and healthy subjects. 20 healthy and 20 T2D subjects were enrolled in the study. miR-21 expression in PBMCs of the subjects was measured using real-time PCR. IL-6 and TNF-α levels in culture supernatants were quantified using ELISA. miR-21 expression was not significantly different between the diabetic and nondiabetic groups. A downregulation of miR-21 expression was observed in PBMCs of obese subjects in both diabetic and nondiabetic groups. In addition, miR-21 expression was negatively correlated with weight, waist circumference, body mass index, and triglyceride in both the diabetic and nondiabetic groups. Our results also demonstrated that the PBMCs of obese subjects significantly secreted a higher level of IL-6 and TNF-α in comparison with the PBMCs of nonobese subjects. Furthermore, a significant inverse correlation between miR-21 expression and TNF-α and IL-6 production from the PBMCs was observed. These data suggest that miR-21 expression is decreased in PBMCs of obese subjects and reduced expression appears to be associated with increased secreted cytokine level in media of PBMCs of obese subjects.

Gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the neurokinin-1 receptor antagonist-based antiemetic regimens: a candidate-gene association study in breast cancer patients.

PURPOSE: The current candidate gene association study aims to investigate tag SNPs from the TACR1 gene as pharmacogenetic predictors of response to the antiemetic guidelines-recommended, NK-1 receptor antagonist-based, triple antiemetic regimens. METHODS: A set of eighteen tag SNPs of TACR1 were genotyped in breast cancer patients receiving anthracycline and cyclophosphamide (with/without docetaxel) applying real-time PCR-HRMA. Data analysis for 121 ultimately enrolled patients was initiated by defining haplotype blocks using PHASE v.2.1. The association of each tag SNP and haplotype alleles with failure to achieve the defined antiemetic regimen efficacy endpoints was tested using PLINK (v.1.9 and v.1.07, respectively) based on the logistic regression, adjusting for the previously known chemotherapy-induced nausea and vomiting (CINV) prognostic factors. All reported p-values were corrected using the permutation test (n = 100,000). RESULTS: Four variants of rs881, rs17010730, rs727156, and rs3755462, as well as haplotypes containing the mentioned variants, were significantly associated with failure to achieve at least one of the defined efficacy endpoints. Variant annotation via in-silico studies revealed that the non-seed sequence variant, rs881, is located in the miRNA (hsa-miR-613) binding site. The other three variants or a variant in complete linkage disequilibrium with them overlap a region of high H3K9ac-promoter-like signature or regions of high enhancer-like signature in the brain or gastrointestinal tissue. CONCLUSION: Playing an essential role in regulating TACR1 expression, gene polymorphisms of TACR1 serve as the potential pharmacogenetic predictors of response to the NK-1 receptor antagonist-based, triple antiemetic regimens. If clinically approved, modifying the NK-1 receptor antagonist dose leads to better management of CINV in risk-allele carriers.

Insight into the Predictive Power of Surrogate Diagnostic Indices for Identifying Individuals with Metabolic Syndrome.

BACKGROUND: This study aimed to assess the diagnostic capability of insulin surrogate measurements in identifying individuals with metabolic syndrome (MetS) and propose applicable indices derived from fasting values, particularly in large study populations. METHODS: Data were collected from the datasets of the Surveillance of Risk Factors of NCDs in Iran Study (STEPS). MetS was defined based on the National Cholesterol Education Program (NCEP) criteria. Various insulin surrogate indices, including Homeostasis Model Assessment (HOMA), Quantitative Insulin Sensitivity Check Index (QUICKI), Fasting glucose to insulin ratio (FGIR), Reynaud, Reciprocal insulin, McAuley, Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-glucose index (TyG), TG/ HDL-C, TG/ BMI, and TG/ WC ratio were assessed. Receiver Operating Characteristic (ROC) curves were used to assess pathologic conditions and determine the optimal cut-off through the highest score of the Youden index. Also, Area Under the Curve (AUC) values were established for each index totally and according to sex, age, and BMI differences. RESULTS: The study population consisted of 373 individuals (49.9% women; 75.1% middle age, 39.1% obese, and 27.3% overweight), of whom 117 (31.4%) had MetS. The METS-IR (AUC: 0.856; 95% CI: 0.817-0.895), TG/ HDL-C (AUC: 0.820; 95% CI: 0.775-0.886), TyG (AUC: 0.808; 95% CI: 0.759-0.857), and McAuley (AUC: 0.804; 95% CI: 0.757-0.852) indices provided the greatest AUC respectively for detection of MetS. The values of AUC for all the indices were higher in men than women. This trend was consistent after data stratification based on BMI categories, middle age, and senile individuals. CONCLUSION: The present study indicated that indices of insulin, including METS-IR, TG/HDLC, TyG, and McAuley, have an equal or better capacity in determining the risk of MetS than HOMA-IR, are capable of identifying individuals with MetS and may provide a simple approach for identifying populations at risk of insulin resistance.

Assessment of Recovery Time Effects on Human Primary Neonatal Dermal Fibroblasts After Exposure to Solar-Simulated Ultraviolet Radiation.

Introduction: Photoaging that is accompanied by gene expression alteration is known as early aging of the skin due to overexposure to natural and/or artificial ultraviolet radiation (UVR). The assessment of gene expression alteration in human primary neonatal dermal fibroblasts depending on recovery time after exposure to solar simulated ultraviolet radiation (ssUVR) is the main aim of this bioinformatic study. Methods: Data are extracted from Gene Expression Omnibus (GEO). The pre-evaluation is done via the GEO2R program. The Significant differentially expressed genes (DEGs) were assessed via protein-protein interaction (PPI) network analysis, and the central genes were identified. The central genes were enriched via gene ontology assessment. Results: Among 224 significant DEGs, 20 central genes including TOP2A, MKI67, BRCA1, HELLS, MAD2L1, ANLN, KIF11, MSH2, KRAS, NCAPG, RFC3, PLK4, WDHD1, BLM, CDKN3, KIF15, SMARCA5, and ATAD2 as hub genes and TOP2A, MKI67, BRCA1, ANLN, KRAS, PLK4, SMARCA5, MMP2, and TLR4 as bottleneck genes were determined. Eight central genes were associated with 16 biological terms. Conclusion: In conclusion, significant differences appeared between gene expression conditions of the cells after 1-day and 5-day recovery. Molecular events include the repair and continuation of photodamages. It is possible to introduce drug targets to prevent the progress of induced damages.

Assessment of NB-UVB Effects on Skin of Atopic Dermatitis Patients: A Network Analysis.

Introduction: Atopic dermatitis is a common inflammatory skin disease which is treated with narrowband ultraviolet B (NB-UVB). Exploring the critical targeted genes in patients by UV radiation is the main aim of this study. Methods: Gene expression profiles of lesional and non-lesional skin samples of atopic dermatitis patients after treatment with NB-UVB and the non-irradiated samples were extracted from the Gene Expression Omnibus (GEO) database and analyzed via protein-protein interaction (PPI) network analysis to find the critical targeted genes. Results: A total of 357 significant differentially expressed genes (DEGs) were included in the PPI network. CTNNB1, SRSF1, YWHAB, SMC3, GNB2, ARF3, UBL7, RAB2A, YWHAE, EIF5B, SNRPE, PPIG, RC3H2, CFL1, SMARCB1. LAPTM5, PRPF40A, and RBBP4 were introduced as hub-bottlenecks. Conclusion: In conclusion, five central genes including SMC3, ARF3, EIF5B, SMARCB1, and LAPTM5 were highlighted as the critical genes in response to NB-UVB radiation in the skin of the treated atopic dermatitis patients. The introduced crucial genes are involved in essential cellular functions such as apoptosis, cell cycle, cell proliferation, and inflammation. It seems that applied NB-UVB radiation is a suitable therapeutic method for atopic dermatitis disease.

Comprehensive investigation of insulin-induced amyloidosis lesions in patients with diabetes at clinical and histological levels: A systematic review.

INTRODUCTION: Insulin-derived amyloidosis (AIns), a skin complication in patients with diabetes, causes impaired insulin absorption. This systematic review aims to get a better understanding of this overlooked condition. METHODS: Comprehensive literature searches were performed in Scopus, PubMed, EMBASE, and Web of Science databases until June 17, 2023. From 19,343 publications, duplicate and irrelevant records were eliminated by title, and the full texts of the remaining studies were examined for validity. Clinical, pathological, and therapeutic findings were extracted from 44 papers. RESULTS: Forty-four articles were studied that covered 127 insulin-treated patients with diabetes. From the 62 patients with reported age and sex, males had a mean age of 58 years, and females 68.5 years. While AIns were twice as likely to develop in men (66.13 %) as in women (33.87 %), the administered insulin dose was significantly higher in males (p = 0.017). The most common insulin injection site was the abdominal wall (77.63 %). Histological findings showed the presence of amorphous material with the occasional presence of lymphocytes, plasma cells, macrophages, adipocytes, histocytes, and giant cells. The mean HbA1c level was 8.8 % and the need for receiving insulin was increased in AIns. Changing the site of insulin injections and/or surgically removing the nodules were the most common treatments to obtain better insulin uptake and controlled serum glucose levels. CONCLUSION: This study highlights the importance of AIns, proper rotation of insulin injection site, and post-treatment patient follow-up to recognize and prevent the development of amyloid nodules.