Age-specific reference intervals for routine biochemical parameters in healthy neonates, infants, and young children in Iran.

Age and sex need to be considered in the establishment of reference intervals (RIs), especially in early life when there are dynamic physiological changes. Since data for important biomarkers in healthy neonates and infants are limited, particularly in Iranian populations, we have determined age-specific RIs for 7 laboratory biochemical parameters. This cross-sectional study comprised a total of 344 paediatric participants (males: 158, females: 186) between the ages of 3 days and 30 months (mean age: 12.91 ± 7.15 months). Serum levels of creatinine, urea, uric acid, calcium, phosphate, vitamin D and high-sensitivity C-reactive protein (hs-CRP) were measured using an Alpha classic-AT plus auto-analyser. We determined age-specific RIs using CLSI Ep28-A3 and C28-A3 guidelines. No sex partitioning was required for any of the biomarkers. Age partitioning was required for kidney function tests and phosphate. The serum concentration of urea and creatinine increased with age, while phosphate and uric acid decreased with age. Age partitioning was not required for serum calcium, vitamin D, and hs-CRP, which remained relatively constant throughout the age range. Age-specific RIs for 7 routine biochemical markers were determined to address critical gaps in RIs in early life to help improve clinical interpretation of blood test results in young children, including neonates. Established age partitions demonstrate the biochemical changes that take place during child growth and development. These novel data will ultimately better disease management in the Iranian paediatric population and can be of value to clinical and hospital laboratories with similar populations.

A large population-based study on the prevalence of electrocardiographic abnormalities: A result of Mashhad stroke and heart atherosclerotic disorder cohort study.

BACKGROUND: Twelve-lead electrocardiogram (ECG) is a common and inexpensive tool for the diagnostic workup of patients with suspected cardiovascular disease, both in clinical and epidemiological settings. The present study was designed to evaluate ECG abnormalities in Mashhad population. METHODS: ECGs were taken as part of MASHAD cohort study (phase1) and were coded according to the Minnesota coding criteria. Data were analyzed using SPSS. RESULTS: Total 9035 ECGs were available for final analysis including 3615 (40.0%) male and 5420 (60.0%) female. Among ECG abnormalities precordial Q wave, major T-wave abnormalities, inferior Q wave, sinus bradycardia, and left axis deviation were the most prevalent abnormalities. The frequency of precordial and inferior Q wave, inferior QS pattern, major and minor ST abnormalities, major and minor T abnormalities, Wolff-Parkinson-White and Brugada pattern, sinus bradycardia, sinus tachycardia, left axis deviation, ST elevation, and tall T wave were significantly different between two genders. Moreover, the frequency of Q wave in precordial and aVL leads, QS pattern in precordial and inferior leads, major and minor T-wave abnormalities, Wolff-Parkinson-White, atrial fibrillation, sinus bradycardia, left axis deviation, and ST elevation were significantly different in different age groups. A comparison of the heart rate, P-wave duration, and QRS duration between men and women indicated that there was a significant difference. CONCLUSIONS: Our finding indicated that the prevalence ECG abnormalities are different between men and women and also it varied in different age groups.

Age-specific reference intervals for liver function tests in healthy neonates, infants, and young children in Iran.

BACKGROUND: The reference intervals (RIs) for liver function tests (LFTs) were determined in Iranian children for the first time. METHODS: A total of 344 healthy pediatrics aged 3 days to 30 months old were recruited. Serum levels of ALT, AST, ALP, direct bilirubin, and total bilirubin were measured. RIs were determined using CLSI Ep28-A3 guidelines. RESULTS: All analytes demonstrated age-specific differences except AST. ALT and ALP demonstrated significantly elevated levels in infants 0 to <5 months relative to the remainder of the age range. Direct and total bilirubin demonstrated markedly elevated levels in early life with mean of 0.28 mg/dL and 1.64 mg/dL observed for direct and total bilirubin, respectively, decreasing by ~50% in the adjacent partition. CONCLUSION: These novel data will help improve the clinical interpretation of biochemical test results in young Iranian neonates and children and can be of value to clinical laboratories with similar populations.

Factors Associated With Trabecular Bone Score and Bone Mineral Density; A Machine Learning Approach.

INTRODUCTION: Bone indexes including trabecular bone score (TBS) and bone mineral density (BMD) have been shown to be associated with wide spectrum of variables including physical activity, vitamin D, liver enzymes, biochemical measurements, mental and sleep disorders, and quality of life. Here we aimed to determine the most important factors related to TBS and BMD in SUVINA dataset. METHODS: Data were extracted from the Survey of Ultraviolet Intake by Nutritional Approach (SUVINA study) including all 306 subjects entered this survey. All the available parameters in the SUVINA database were included the analysis. XGBoost modeler software was used to define the most important features associated with bone indexes including TBS and BMD in various sites. RESULTS: Applying XGBoost modeling for 4 bone indexes indicated that this algorithm could identify the most important variables in relation to bone indexes with an accuracy of 92%, 93%, 90% and 90% respectively for TBS T-score, lumbar Z-score, neck of femur Z-score and Radius Z-score. Serum vitamin D, pro-oxidant-oxidant balance (PAB) and physical activity level (PAL) were the most important factors related to bone indices in different sites of the body. CONCLUSIONS: Our findings indicated that XGBoost could identify the most important variables with an accuracy of >90% for TBS and BMD. The most important features associated with bone indexes were serum vitamin D, PAB and PAL.

The effects of high dose vitamin D supplementation as a nutritional intervention strategy on biochemical and inflammatory factors in adults with COVID-19: Study protocol for a randomized controlled trial.

Introduction: Low serum vitamin D has been shown to be a risk factor for Coronavirus 2019 (COVID-19). The aim of this study was to assess the effects of high dose vitamin D supplementation on hs-CRP, ESR and clinical outcomes, including duration of hospitalization, quality of life and New York Heart Association (NYHA) Functional Classification, in adults with COVID-19. Methods: This double-blind, randomized control trial will be conducted on patients with RT-PCR and/or chest CT scan diagnosis of COVID-19 admitted in Imam Reza Hospital, Mashhad, Iran. Participants will be randomized into control and intervention groups based on randomization sampling. The intervention group will receive soft gel containing 50,000 IU vitamin D on the first day followed by 10,000 IU/day through a supplement drop daily for 29 days. The control group will receive 1000 IU vitamin D daily through supplement drop and a placebo soft gel. All participants will undergo laboratory assessment including inflammatory markers, serum 25)OH)D, complete blood count (CBC), liver and renal profile, lipid profile and erythrocyte sedimentation rate (ESR) at baseline and at day 30. The mortality rate will be recorded in both groups. Results: Data will be presented using descriptive statistics. Comparison of changes in study parameters over the study period will be performed using analysis of covariance adjusting for possible confounders. Conclusions: The findings of this will provide evidence on the effects of high dose vitamin D supplementation on inflammatory markers in hospitalized COVID-19 patients.

Reference intervals for routine biochemical markers and body mass index: A study based on healthcare center database in northeastern Iran.

Age- and sex-specific reference intervals (RIs) for some biochemical tests may be useful for their interpretation, due to the variations in lifestyle and genetic, or ethnic factors. The aim of this study was to obtain RIs for some routine biochemical markers including a serum lipid profile, fasting blood glucose (FBG), aspartate and alanine aminotransferase (AST and ALT), uric acid, and body mass index (BMI) in subjects who attended primary healthcare centers. The large database of primary healthcare centers uses RIs to report results for children, adolescents, and young and old adults. RIs were obtained by using the indirect method, recommended by the CLSI Ep28-A3 guidelines. RIs for FBG, BMI, and serum lipid profile, including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol in people aged 18 to 120 years, were obtained without age/sex segmentation. RIs for serum AST, ALT, and uric acid were obtained without age segmentation, though these RIs were higher in males than females. The RIs for AST, ALT, and uric acid were higher in men, while the RIs for the other variables were similar in both sexes. This is the first study reporting the use of indirect RIs for BMI.

Effect of acute and chronic stress on memory impairment and hippocampal oxidative stress following global cerebral ischemia in adult male rats.

Background and purpose: Stress, especially immobility stress, is quite common and one of the most important and influential risk factors in neurological disorders. This study aimed to investigate the effect of acute and chronic immobility stress on the level of cortical and hippocampal oxidative stress indicators and memory impairment following global cerebral ischemia. Experimental approach: In this study, 48 male Wistar rats were randomly divided into 6 groups: 1, sham (S); 2, sham-acute stress (SSA); 3, sham-chronic stress (SSC); 4, ischemia (IS); 5, ischemia-acute stress (ISA); 6, ischemia-chronic stress (ISC). The Morris water maze (MWM) test was performed 14 days after surgery, and cortisol levels and oxidative stress factors such as malondialdehyde MDA and total thiol were measured. Findings/Results: In the MWM test, the time to find the platform (latency time) in the ISC and IS groups significantly increased compared to the S group. The time spent in the target quarter in these two groups was significantly reduced compared to the S group on the day of the probe. The results showed a significant increase in cortisol levels and malondialdehyde concentration in the ISA, ISC, and IS groups compared to the S group, but there was no significant difference in total thiol concentration. No significant difference was observed in the level of oxidative stress factors in the cortex. Conclusion and implication: Chronic immobility stress could reduce antioxidant factors in the hippocampus and exacerbate memory impairment caused by global ischemia.

The effect of SP/NK1R on expression and activity of glutaredoxin and thioredoxin proteins in prostate cancer cells.

Substance P (SP), an important neuropeptide, has a crucial role in the progression of several cancers, including prostate cancer, through interacting with the neurokinin-1 receptor (NK1R). Oxidative stress is also involved in the onset and progression of prostate cancer. However, no studies have been performed on the cross-talk between the SP/NK1R system and cellular redox balance in prostate cancer, and how it is involved in tumorogenesis. We aimed to investigate the effect of the SP/NK1R system and the blockage of NK1R with its specific antagonist (aprepitant) on the cellular redox status of the prostate cancer cell line (PC3 and LNCaP). We performed the resazurin assay to evaluate the toxicity of the aprepitant on the PC3 and LNCaP cell lines. The intracellular reactive oxygen species (ROS) level was measured after SP and aprepitant treatment. The alterations of expression and activity of two crucial cellular oxidoreductases, glutaredoxin, and thioredoxin were evaluated by qRT-PCR and commercial kits (ZellBio GmbH), respectively. Our results revealed that SP increased ROS production and decreased the expression and activity of glutaredoxin and thioredoxin. On the other hand, treatment of cells with aprepitant showed reverse results. In conclusion, we found that the SP/NK1R system could promote prostate cancer progression by inducing oxidative stress. In addition, the inhibition of NK1R by aprepitant modulated the effect of the SP/NK1R system on the cellular redox system. Aprepitant might therefore be introduced as a candidate for the treatment of prostate cancer; however, more studies are required to confirm the validation of this hypothesis.

The SP/NK1R system promotes the proliferation of breast cancer cells through NF-κB-mediated inflammatory responses.

BACKGROUND: Numerous molecules have been introduced to participate in the formation of breast cancer, the most common malignancy in women. Among them, neuropeptide substance P (SP) and its related receptor neurokinin-1 receptor (NK1R) have attracted unprecedented attention in tumorigenesis processes. In this study, we investigated the effect of the SP/NK1R pathway on the induction of oxidative stress in breast cancer and examine the therapeutic potential of NK1R inhibition in this malignancy. METHODS: MCF-7 cells were treated with varying concentrations of SP and aprepitant, an FDA-approved NK1R antagonist, either as a single drug or in a combined modality. Resazurin assay was used to evaluate the anti-cancer ability of aprepitant. The alteration in the intracellular levels of reactive oxygen species (ROS) and gene expression were determined using ROS assay and the qRT-PCR analysis, respectively. RESULTS: The stimulation of the SP/NK1R axis in the MCF-7 cells was coupled with the accumulation of ROS as well as upregulation of NF-κB and its related pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α and IL-6. In contrast, the suppression of NK1R by aprepitant halted the viability of MCF-7 cells, at least partly due to p53-mediated upregulation of p21. Moreover, aprepitant attenuated the oncogenic properties of SP by preventing the oxidative property of this neuropeptide. CONCLUSION: Overall, our results suggest that the SP/NK1R pathway might play a critical role in breast cancer pathogenesis, probably through inducing ROS/NF-κB-mediated inflammatory responses. Moreover, it seems that blockage of the axis has promising therapeutic value against breast cancer cells. Schematic representation proposed for the plausible mechanism by which the stimulation of the SP/NK1R might induce oxidative stress in breast cancer-derived MCF-7 cells. Once SP interacts with NK1R, this signaling axis could disturb the balance between the expression of p53 and NF-κB, an event that leads to the accumulation of ROS within MCF-7 cells. The produced ROS, in turn, elevates the expression of pro-inflammatory cytokines (TNF-α and IL-6) and downregulates the expression of p21. On the other hand, aprepitant, an antagonist of NK1R, could reduce the survival of proliferative capacity of MCF-7 cells by decreasing the intracellular levels of ROS and p53-mediated up-regulation of p21. Along with the effect on p53, aprepitant could also reduce the expression of NF-κB and its related pro-inflammatory cytokines.

The anti-tumoral role of Hesperidin and Aprepitant on prostate cancer cells through redox modifications.

Prostate cancer is the second prevalent cancer in men. While the anti-cancer effect of Hesperidin and (Aprepitant) AP on prostate cancer cells is well documented, their combined effect and their mechanism of action are not fully investigated. Therefore, this study aimed to investigate the anti-cancer effects of Hesperidin and AP alone and in combination on prostate cancer cells. PC3 and LNCaP cell lines were treated with Hesperidin and AP alone and in combination. The Resazurin test was used for assessing cell viability. The ROS (reactive oxygen Species) level, P53, P21, Bcl-2, and Survivin gene expression were assessed. Also, a trypan blue assay was done. Hesperidin and AP reduced cell viability and increased apoptosis in PC3 and LNCaP cells. The ROS level reduced after treating the PC3 and LNCaP cells with AP with or without Hesperidin. P53 and P21 gene expression increased after treatment with Hesperidin with or without AP compared to the untreated group in the PC3 cell line. Bcl-2 and Survivin gene expression decreased with AP with or without Hesperidin in the PC3 and LNCaP cells. The current study showed the synergic anti-cancer effect of Hesperidin and AP in both PC3 and LNCaP cell lines.

The Effects of Lycopene on Modulating Oxidative Stress and Liver Enzymes Levels in Metabolic Syndrome Patients: A Randomised Clinical Trial.

OBJECTIVE: The pathogenesis of metabolic syndrome (MetS) complications involves the excessive production of
reactive oxygen species, inflammation, and endothelial dysfunction. Due to Lycopene, a highly unstable structure and
its significant effects on modulating the metabolic system, there is a strong need for a formula that can increase its
stability. The aim of this study was to develop an approach for encapsulating Lycopene and investigate its effects on
inflammatory markers, oxidative stress, and liver enzymes in patients with MetS.
Materials and Methods: This study is a simple randomized, double-blind, objective-based clinical trial that involved
eighty subjects with MetS, who were equally and randomly assigned to two groups: one group received 20 mg of
Lycopene per day for 8 weeks, and the Placebo group followed the same protocol as the Lycopene group but received
a placebo instead of Lycopene. They were called Lycopene and placebo, respectively. During follow-up visits after 4
and 8 weeks, 20 ml of blood was collected for evaluation of liver enzymes and some inflammatory related markers.
Results: Prior to the assignment of volunteers to their respective groups, there were no notable differences in C-reactive
protein (CRP), serum liver enzymes, systolic and diastolic blood pressure, or pro-oxidant-antioxidant balance (PAB)
between the Lycopene and placebo groups. However, our subsequent analysis revealed a significant reduction in the
serum levels of CRP (P=0.001) and PAB (P=0.004) in the group that received Lycopene. Our encapsulated Lycopene
treatment was not associated with a significant difference in serum levels of alanine aminotransferase (ALT), aspartate
transferase (AST), or alkaline phosphatase (ALP) between our two groups.
Conclusion: This study investigated the impact of Lycopene on individuals with MetS, revealing a noteworthy
modulation effect on PAB and inflammation linked to MetS. However, no significant differences was demonstrated in
serum levels of ALT, AST and ALP between the studied group (registration number: IRCT20130507013263N3).

Higher dietary acid load is associated with an increased risk of metabolic syndrome.

There have been inconsistent reports regarding the association between dietary acid load and Metabolic Syndrome (MetS). We aimed to investigate the association between dietary acid load and MetS in an Iranian adult population. In this cross-sectional study, 1945 participants aged 35-65 years were recruited from MASHAD cohort study. Dietary intakes were assessed using a 24-h dietary recall. Diet-based acidity was assessed as the net endogenous acid production (NEAP), potential renal acid load (PRAL), and dietary acid load (DAL). To define MetS, the International Diabetes Federation (IDF) criteria were used. Multivariable logistic regression models were applied to determine the association between diet-based acid load scores and MetS. Participants' mean age and BMI were 47.13 ± 7.78 years and 27.57 ± 4.48 kg/m2, respectively. Around 57% of the population was female. Overall, 31.9% had MetS. According to the full-adjusted model, there was a significant association between higher quartiles of PRAL, NEAP, and DAL and MetS (Q4 PRAL; OR (95%CI) 1.42(1.05-1.91), Q4 NEAP; OR (95%CI) 1.48(1.11-1.98), Q4 DAL; OR (95%CI) 1.44(1.05-1.91)). This study showed a significant positive association between different dietary acid load indicators (PRAL, NEAP, and DAL) and odds of MetS among Iranian adults.

Pediatric reference intervals for hematology parameters in healthy infants and young children in Iran.

INTRODUCTION: Defining accurate age- and sex-specific reference intervals (RIs) for hematology parameters, especially for the pediatric population, is important for making an appropriate clinical diagnosis. To address gaps, we established age-specific RIs for 11 hematologic parameters in Iranian children younger than 30 months for the first time. METHODS: Fresh whole blood samples collected from a total of 344 participants (males: 158 and females: 186) ages 3 days to 30 months, with a mean age of 12.91 ± 7.15 months, were recruited from healthcare centers in Mashhad, Iran. Hematologic parameters, including complete blood count (CBC), were analyzed on the Sysmex auto-analyzer system (KX-21 N). RIs were calculated with 90% confidence intervals using the direct method based on CLSI Ep28-A3 and C28-A3 guidelines. RESULTS: None of the CBC parameters required sex partitioning. Of 11 CBC parameters, six required age partitions of 3 days-<4 months, 4-<10, 10-<15, and 4-<30 months. Five parameters (i.e., white blood cell count, mean corpuscular hemoglobin concentration, mean platelet volume, red cell distribution width, and platelet distribution width) did not demonstrate age-specific changes. RIs of red blood cell count and hematocrit, as well as hemoglobin, increased with age, while mean corpuscular volume, mean corpuscular hemoglobin, and platelet count, decreased with age. CONCLUSION: In this study, we established RIs for 11 hematology parameters in young children. Age partitioning was required for six parameters demonstrating marked changes during the early period of growth and development and necessitating the use of pediatric-specific reference standards.

Mesenchymal stem cell therapy in amyotrophic lateral sclerosis (ALS) patients: A comprehensive review of disease information and future perspectives.

Amyotrophic lateral sclerosis (ALS) is a rare deadly progressive neurological disease that primarily affects the upper and lower motor neurons with an annual incidence rate of 0.6 to 3.8 per 100,000 people. Weakening and gradual atrophy of the voluntary muscles are the first signs of the disease onset affecting all aspects of patients' lives, including eating, speaking, moving, and even breathing. Only 5-10% of patients have a familial type of the disease and show an autosomal dominant pattern, but the cause of the disease is unknown in the remaining 90% of patients (Sporadic ALS). However, in both types of disease, the patient's survival is 2 to 5 years from the disease onset. Some clinical and molecular biomarkers, magnetic resonance imaging (MRI), blood or urine test, muscle biopsy, and genetic testing are complementary methods for disease diagnosis. Unfortunately, with the exception of Riluzole, the only medically approved drug for the management of this disease, there is still no definitive cure for it. In this regard, the use of mesenchymal stem cells (MSCs) for the treatment or management of the disease has been common in preclinical and clinical studies for many years. MSCs are multipotent cells having immunoregulatory, anti-inflammatory, and differentiation ability that makes them a good candidate for this purpose. This review article aims to discuss multiple aspects of ALS disease and focus on MSCs' role in disease management based on performed clinical trials.

The Therapeutic Potential of Aprepitant in Glioblastoma Cancer Cells through Redox Modification.

Although there is no doubt regarding the involvement of oxidative stress in the development of glioblastoma, many questions remained unanswered about signaling cascades that regulate the redox status. Given the importance of the substance P (SP)/neurokinin 1 receptor (NK1R) system in different cancers, it was of particular interest to evaluate whether the stimulation of this cascade in glioblastoma-derived U87 cells is associated with the induction of oxidative stress. Our results showed that SP-mediated activation of NK1R not only increased the intracellular levels of malondialdehyde (MDA) and reactive oxygen species (ROS) but also reduced the concentration of thiol in U87 cells. We also found that upon SP addition, there was a significant reduction in the cells' total antioxidant capacity (TAC), revealing that the SP/NK1R axis may be involved in the regulation of oxidative stress in glioblastoma cells. The significant role of SP/NK1R in triggering oxidative stress in glioblastoma has become more evident when we found that the abrogation of the axis using aprepitant reduced cell survival, probably through exerting antioxidant effects. The results showed that both MDA and ROS concentrations were significantly reduced in the presence of aprepitant, and the number of antioxidant components of the redox system increased. Overall, these findings suggest that aprepitant might exert its anticancer effect on U87 cells through shifting the balance of oxidant and antioxidant components of the redox system.

The Effect of SP/NK1R on the Expression and Activity of Catalase and Superoxide Dismutase in Glioblastoma Cancer Cells.

INTRODUCTION: Glioblastoma is the most malignant brain tumor with different therapeutic protocols, including surgery, radiotherapy, and chemotherapy. Substance P (SP), a peptide released by sensory nerves, increases cellular excitability by activating the neurokinin-1 receptor (NK1R) in several human tumor cells. Aprepitant is a potent and long-lasting NK1R antagonist, considered a new agent for inhibiting proliferation and induction of apoptosis in malignant cells. This study aimed to evaluate the effects of the SP/NK1R system on the expression and activity of catalase and superoxide dismutase (SOD) in the glioblastoma U87 cancer cell line. METHODS: Cytotoxicity was measured by the resazurin test, 24 hours after treatment, with increasing aprepitant concentrations. The production of reactive oxygen species (ROS) was also measured 24 hours after treatment with SP and aprepitant. Enzymes activity of catalase and SOD was measured using the corresponding assay kits. Real-time PCR also measured their expression. RESULTS: Aprepitant significantly reduced the viability of U87 cells in a concentration-dependent manner. ROS production was significantly reduced, and the activity of catalase and SOD increased after treatment with aprepitant. The expression of catalase and SOD enzymes also increased significantly in the presence of aprepitant. CONCLUSION: The present study showed that aprepitant inhibited SP's oxidizing effects via inducing the antioxidant effects of catalase and SOD in the U87 cell line. Therefore, this drug might be introduced as a potential candidate for controlling glioblastoma cancer in animal models and clinical trials.

The effects of consuming a low-fat yogurt fortified with nano encapsulated vitamin D on serum pro-oxidant-antioxidant balance (PAB) in adults with metabolic syndrome; a randomized control trial.

BACKGROUND AND AIM: The current study aimed to assess the effect of fortified yogurt with nano-encapsulated vitamin D on serum pro-oxidant anti-oxidant balance (PAB) in adults with or without metabolic syndrome. METHODS: In a quadruple blind clinical trial study, 139 adults with an age range of 30-50 years were randomly selected to receive either 1500 IU nano-encapsulated vitamin D fortified yogurt or placebo for ten weeks. Before and after the intervention period, blood sample was taken to determine the serum levels of vitamin D, pro-oxidant-antioxidant balance (PAB), and high-sensitivity C-reactive protein (hs-CRP). The laboratory tests were checked at baseline and at the end of the treatment. RESULTS: Serum vitamin D increased significantly, from 14.47 ± 6.07 ng/mL to 21.39 ± 6.54 ng/mL (P < 0.001) after ten weeks in the intervention group. Serum hs-CRP and PAB were significantly lower following consumption period in intervention group [1.95(0.4-8.15) g/dL vs. 1.35(0.25-3.62) g/dL; P = 0.013] and (135.19 ± 42.4 HK vs. 115.39 ± 44.69) HK; P = 0.018] respectively. There were no significant differences between the intervention and control groups regarding weight and BMI at the end of the intervention period (p > 0.05). CONCLUSION: Low-fat yogurt fortified with nano-encapsulated vitamin D was found to reduce serum PAB levels in adults with metabolic syndrome. PRACTICAL APPLICATION: The findings of the present study indicated that a low-fat yogurt fortified with 1500 IU nano-encapsulated vitamin D for ten weeks, leads to a significant reduction in serum hs-CRP and PAB concentrations highlighted the anti-inflammatory/anti-oxidative effect of vitamin D.

Isothermal titration calorimetry and stopped flow circular dichroism investigations of the interaction between lomefloxacin and human serum albumin in the presence of amino acids.

The present study was designed to investigate the influence of two indispensable and two dispensable amino acids, including methionine, histidine, cysteine and proline, on the binding interaction between human serum albumin (HSA) and an antibiotic agent lomefloxacin (LMF). The fluorescence quenching experiments showed that the intrinsic emission of HSA was considerably quenched following binding to LMF in all the systems. Furthermore, in all the interactions the maximum wavelength of HSA was slightly decreased. The spectral changes observed in the binding systems we e all attributed to the alteration of the micro-environment around the tryptophan and tyrosine residues of HSA. The Kb values o HSA-LMF complex in the absence and presence of histidine, methionine, cysteine and proline have been obtained 6.02 × 105, 4.83 × 105, 5.05 × 105, 4.94 × 105 and 6.20 × 105 M-1 respectively. The various kind of Kb values showed the different interaction behavior between HSA and LMF in the absence and presence of amino acids mentioned. The data gathered by isothermal titration calorimetry (ITC) studies revealed that although all the binding interactions were exothermic, the amount of the heat exchanged during the HSA-LMF interaction increased in the presence of the amino acids especially cysteine. In the present study, the binding kinetics and affinity of LMF to HSA in the absence and presence of the amino acids were studies using stopped-flow circular dichroism and ITC techniques respectively. The results of these two techniques revealed that the bindig affinity and binding rate of the LMF-HSA interaction decreased in the presence of histidine, methionine and cysteine. In the presence of proline, the binding process of LMF-HSA was sped up and the affinity of LMF to HSA slightly increased. All the experimental results were then supported by the data collected from molecular modeling studies using density functional theory. Communicated by Ramaswamy H. Sarma.

Multi-spectroscopic and molecular modeling studies of interaction between two different angiotensin I converting enzyme inhibitory peptides from gluten hydrolysate and human serum albumin.

The present study was carried out to characterize Angiotensin-converting enzyme (ACE) inhibitory peptides which are released from the trypsin hydrolysate of wheat gluten protein. The binding of two inhibitory peptide (P4 and P6) to human serum albumin (HSA) under physiological conditions has been investigated by multi-spectroscopic in combination with molecular modeling techniques. Time-resolved and quenching fluorescence spectroscopies results revealed that the quenching of HSA fluorescence by P4 and P6 in the binary and ternary systems caused HSA-peptides complexes formation. The results indicated that both peptides quenched the fluorescence intensity of HSA through a static mechanism. The binding affinities and number of binding sites were obtained for the HSA-peptides complexes. The circular dichroism (CD) data revealed that the presence of both peptides increased the α-helix content of HSA and induced the remarkable folding of the polypeptide of the protein. Therefore, the CD data determined that the protein structure has been stabilized in the percent of ACE inhibitory peptides in binary and ternary systems. The binding distances between HSA and both peptides were estimated by the Forster theory, and it was revealed that nonradiative energy transfer from HSA to peptides occurred with a high probability. ITC experiments reveal that, in the absence and presence of P6, the dominant forces are electrostatic in binary and ternary systems. Furthermore, molecular modeling studies confirmed the experimental results. Molecular modeling investigation suggested that P4 bound to the site IA and IIA of HSA in binary and ternary systems, respectively. This study on the interaction of peptides with HSA should prove helpful for realizing the distribution and transportation of food compliments and drugs in vivo, elucidating the action mechanism and dynamics of food compliments and drugs at the molecular level. It should moreover be of great use for understanding the pharmacokinetic and pharmacodynamic mechanism of the food compliments and drugs.

Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques.

The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-benzene sulfonamide (HBS1), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS2), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS3) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the KSV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The KSV1 ans KSV2 values of HBS derivatives with Hb are .6 × 1013 and 3 × 1013 M-1 for Hb-HBS1, 1 × 1013 and 4 × 1013 M-1 for Hb-HBS2, .9 × 1013, and 6 × 1013 M-1 for Hb-HBS3, respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster's theory of dipole-dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb-HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.