Immunomodulatory, anti-inflammatory, and antioxidant effects of curcumin

Turmeric is a widely used spice derived from the rhizomes of Curcuma longa. Having been used as a dietary spice, it has drawn scientists’ attention to the possible medicinal benefits of its active compounds called curcuminoids which consist of curcumin, demethoxycurcumin and bisdemethoxycurcmin. Considering wide range of pharmacological properties that curcumin offers, numerous studies have investigated its potency as a therapeutic agent in various diseases such as autoimmune, cardiovascular, neoplastic, pulmonary, neurodegenerative and metabolic diseases. With regard to its wide array of health benefits and published data on the underlying mechanisms of its action, a complex interaction between three main events including inflammation, oxidative stress, and immunity, seems to contribute to different therapeutic roles of this compound. Hence, this review discusses the current knowledge on the anti-inflammatory, antioxidant, and immunomodulatory roles of curcumin with the hope of recruiting curcumin as a therapeutic agent in future therapeutic regimen in order to enhance the efficacy of the treatment, as well as decreasing the adverse effects of synthetic chemical drugs

Serum Procalcitonin and Lactoferrin in Detection of Acute Appendicitis; a Diagnostic Accuracy Study

Introduction: Finding an accurate diagnostic test can reduce the rate of unnecessary abdominal surgery in cases of suspected acute appendicitis (AA). This study aimed to evaluate the diagnostic value of serum lactoferrin (LF) and procalcitonin (PCT) in detection of patients with acute appendicitis.Methods: In this diagnostic accuracy study, screening performance characteristics of PCT and LF were calculated in patients suspected with acute appendicitis and healthy volunteers as control group.Results: 131 cases participated (61 as case and 70 as control). The mean serum level of LF (0.9±0.14 vs 0.2±0.13 µg/ml; p 0.0001) and PCT (0.15±0.21 vs 0.11±0.02 ng/dl; p = 0.02) were significantly higher in patients suspected with AA. The AUC of PCT and LF were 0.46 (95% CI: 0.31-0.61) and 0.61 (95%CI: 0.47 - 0.76), respectively. At a 0.90 µg/ml cut-off value, LF had 77% (95 % CI: 63 - 91) sensitivity and 43% (95 % CI: 31 - 55) specificity. Also, at a 0.11 ng/dl cut-off value, PCT had 41% (95 % CI: 26 - 56) sensitivity and 69% (95 % CI: 53 - 85) specificity.Conclusion: Based on the main finding of present study, the overall accuracy of serum PCT and LF in detection of patients with acute appendicitis are in poor to failed range and it seems that they could not be considered as good screening tools for this purpose

Effects of Major Ingredients in Cattle Milk on Enzyme Kinetics of Recombinant β-galactosidase (BGalP) Expressed in Pichia pastoris

Background and objective: β-galactosidase enzymes hydrolyze lactose into glucose and galactose for production of lactose free dairy products. However, different ions and fat content in milk may act as the inhibitor or activator for β-galactosidase enzymes. A cold-active β-galactosidase enzyme (BGalP), originally from Planococcus sp. L4, was previously expressed in Pichia pastoris to perform lactose hydrolysis in the refrigerated milk. In this study, the effects of milks major ingredients were evaluated on the enzymatic kinetics to confirm its capacity for hydrolyzing milk lactose.Material and methods: The activity was determined in different concentrations of NaCl, KCl, MgCl2, and CaCl2 as well as in the milk with low, medium or high-fat content. In these experiments ortho-Nitrophenyl β-galactoside was used as the substrate. Additionally, glucose was measured as the product after incubation of milk with BGalP enzyme for 24 h at room temperature.Results and conclusion: This study demonstrated that ions and fat content did not adversely affect the enzyme activity in the concentration corresponding to the milk contents. Ca (27.5-32.5 mM), Cl (25.3-30.9 mM), Na (15.2-39.1 mM) and Mg (3.75-5.83 mM) had no inhibitory effects, but KCl decreased the enzyme activity. Since Cl existed in MgCl2, and CaCl2 exerted no inhibitory effects, it can be concluded that inhibitory effects of KCl resulted from potassium rather than chloride. The results indicate that BGalP enzyme was not inhibited by milks major ingredients and has the potential to be used for the production of lactose-free dairy products.Conflict of interest: The authors declare no conflict of interest

Burn-induced Oxidative Stress and Serum Glutathione Depletion; a Cross Sectional Study

Introduction: Several studies have shown the role of oxidative stress in pathophysiology of burn injuries. This study aimed to evaluate the changes of oxidant-antioxidant levels during the week following burn injuries and its correlation with grade of burn. Methods: In this prospective cross-sectional study, changes of total glutathione, reduced glutathione (GSH), oxidized GSH (GSSG), GSH/GSSG ratio, as well as Pro-oxidant-antioxidant balance (PAB) were investigated on the 1st, 2nd and 7th days of admission in patients with > 15 % burns.Results: 40 patients with the mean age of 21.1 ± 14.5 were studied (47.5% male). More than 50% of patients were in the 18 – 55 years age range and over 70% had 20% – 60% grade of burn. Total serum glutathione level and GSH had significant decreasing trends (P < 0.001) and GSSG and GSH/GSSG ratio had increasing trends (p < 0.001). No significant correlation was observed between serum GSH level and the total body surface area (TBSA) of burn injury (r = 0.047; p = 0.779). The evaluation of PAB and its correlation with TBSA showed a significant and direct association between them on the 1st (coefficient = 0.516; p = 0.001), 2nd (coefficient = 0.62; p <0.001), and 3rd (coefficient = 0.471; p = 0.002) day of follow up.Conclusion: According to this study, the redox perturbation occurred in burn injury which was measured and proved by decreased GSH/GSSG ratio as well as the shift of PAB in favour of oxidants. Besides, since PAB positively correlated with the severity of dermal damage, it might suggest the application of antioxidants as a part of therapeutic protocol for which the dosage should be proportionate to the surface area of the damaged skin.

Evaluation of Antioxidant Capacity and Cotinine Levels of Saliva in Male Smokers and Non-smokers

Background: The cigarette compounds are associated with the increase in the incidence of oral cancer andprecancerous lesions. Salivary antioxidant system plays an important role in anti-carcinogenic capacity ofsaliva. Cotinine, a nicotine metabolite, has a longer half-life in comparison with nicotine and is a suitablemarker for exposure to cigarette smoke. This study aims to measure total antioxidant capacity (TAC) andcotinine level in saliva of smokers and non-smokers and compare salivary cotinine level and TAC in each grou.Methods: In this cross-sectional study, 32 smokers and 34 non-smokers were recruited by consecutivesampling from Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences,Mashhad, Iran. Salivary cotinine and TAC concentrations were determined using the enzyme-linkedimmunosorbent assay (ELISA) technique. For data analysis, correlation tests of Spearman, Mann-WhitneyU, and independent samples t-test were used.Findings: A significant difference was observed between the two groups in the mean cotinine level and in themean TAC (P = 0.015, P = 0.027, respectively). TAC showed a weak negative correlation with the cotininelevel, but the difference was not significant (P = 0.651).Conclusion: Antioxidants are of great importance to smokers because antioxidants are able to scavenge freeradicals found in cigarette smoke. According to the results of present study, the salivary TAC in smokers waslower than that of non-smokers, and the salivary cotinine level in smokers was higher than non-smokers.Therefore, smoking endangers the oral cavity health by reducing the salivary TAC. Further studies with ahigher sample size and other factors affecting the salivary TAC are needed for definitive comment

Regulation of human thioredoxin and glutaredoxin systems by oxidation and S-nitrosylation

The homeostasis of intracellular redox status has a crucial role in the cell survival and different processes such as DNA synthesis, gene expression, enzymatic activity, etc. This homeostasis is achieved via an intense balance between pro-oxidants and anti-oxidants. Among anti-oxidants, there are two enzymatic systems which are also the main intracellular general protein disulfide reductases, the thioredoxin (Trx) and glutaredoxin (Grx) systems. The Trx system contains Trx, Trx reductase (TrxR) and NADPH, while the Grx system is composed of glutathione (GSH), glutathione reductase (GR), Grx and NADPH. The upregulation of Trx, TrxR, and Grx have been reported in various tumor cells that are directly correlated to the resistance to chemotherapy, aggressive tumor growth and poor prognosis. Therefore, these two systems are potential targets for anti-tumor therapy as well as some other clinical applications. Hence, it is important to know how the activity and structure of these proteins are affected via chemical compounds or by post-translational modifications. Motexafin gadolinium (MGd), a new chemotherapeutic drug, was an NADPH oxidizing substrate for mammalian TrxRs with a Km-value of 8.65 μM (kcat/Km of 4.86 × 104 M-1s-1). The reaction involved redox cycling of MGd by oxygen producing superoxide and hydrogen peroxide. MGd acted as a non-competitive inhibitor (IC50 of 6 μM) for rat TrxR. MGd was a better substrate (kcat/Km of 2.23 × 105 M-1 s-1) for TrxR from E. coli and a strong inhibitor of Trx-dependent protein disulfide reduction. Direct reaction between MGd and reduced Trx from either human or E. coli was negligible. Ribonucleotide reductase (RNR) is an essential enzyme for DNA synthesis. MGd inhibited recombinant mouse RNR activity with either 3 μM reduced human Trx (IC50 2 μM) or 4 mM dithiothreitol (IC50 6 μM) as electron donors. Our results may explain the effects of the drug on cancer cells, which often overproduce TrxR and have induced RNR for replication and repair. Besides two cysteines in the active site, human cytosolic Grx1 and mitochondrial Grx2 contain three and two additional structural cysteines, respectively. We analyzed the redox state and disulfide pairing of Cys residues upon GSSG oxidation and S-nitrosylation. Grx1 was partly inactivated both by S-nitrosylation and oxidation. Inhibition by nitrosylation was reversible under anaerobic conditions; aerobically it was stronger and irreversible, due to nitration. Oxidation of Grx1 induced a complex pattern of disulfide bonded dimers and oligomers formed between Cys 8 and either Cys 79 or Cys 83. An intramolecular disulfide between Cys 79 and Cys 83 was also identified. Grx2 retains activity upon oxidation, did not form dimers or oligomers and could not be S-nitrosylated. The dimeric iron sulfur cluster coordinating inactive form of Grx2 dissociated upon nitrosylation, leading to activation of the protein. Besides active site cysteines in the conserved motif of -Cys-Gly-Pro-Cys-, human cytosolic Trx1 has three structural Cys residues in positions 62, 69 and 73 which upon diamide oxidation induce a second Cys 62-Cys 69 disulfide as well as dimers and multimers. After incubation with H2O2, only monomeric two-disulfide molecules are generated which are inactive but able to regain full activity in an autocatalytic process in the presence of NADPH and TrxR. We found that nitrosylation by GSNO at physiological pH is critically dependent on the redox state of Trx. Starting from fully reduced human Trx, both Cys 69 and Cys 73 were nitrosylated and the active site formed a disulfide; the nitrosylated Trx was not a substrate for TrxR but regained activity after a lag phase consistent with autoactivation. The reversible inhibition of human Trx1 activity by H2O2 and NO donors is suggested to act in cell signaling via temporal control of reduction for the transmission of oxidative and/or nitrosative signals in thiol redox control

The effect of Ramadan fasting on endocrine system.

In the religion of Islam, fasting is obligatory for healthy adults during Ramadan. Millions of Muslims around the world practice fasting in this holy month which may cause different metabolic and hormonal changes due to the restrictions in regular caloric intake. This article was aimed to review some possible effects of Ramadan fasting on the endocrine system which has a great impact on physiological and cellular processes through a wide variety of hormones. Despite various studies regarding the impact of Islamic fasting on a number of hormonal values, yet there is not any obvious consensus on its impact on human health. In conclusion, this article recommended normal people to continue fasting during this holy month because despite the modifications that occur in the secretion pattern of some hormones, it causes no major alteration in the health of normal subjects; it is also effective for maintenance of remission in some diseases

Immunomodulatory, anti-inflammatory, and antioxidant effects of curcumin

Turmeric is a widely used spice derived from the rhizomes of Curcuma longa. Having been used as a dietary spice, it has drawn scientists’ attention to the possible medicinal benefits of its active compounds called curcuminoids which consist of curcumin, demethoxycurcumin and bisdemethoxycurcmin. Considering wide range of pharmacological properties that curcumin offers, numerous studies have investigated its potency as a therapeutic agent in various diseases such as autoimmune, cardiovascular, neoplastic, pulmonary, neurodegenerative and metabolic diseases. With regard to its wide array of health benefits and published data on the underlying mechanisms of its action, a complex interaction between three main events including inflammation, oxidative stress, and immunity, seems to contribute to different therapeutic roles of this compound. Hence, this review discusses the current knowledge on the anti-inflammatory, antioxidant, and immunomodulatory roles of curcumin with the hope of recruiting curcumin as a therapeutic agent in future therapeutic regimen in order to enhance the efficacy of the treatment, as well as decreasing the adverse effects of synthetic chemical drugs

Salivary Biomarkers: Noninvasive Ways for Diagnosis of Parkinson’s Disease

Finding reliable biomarkers has a crucial role in Parkinson’s disease (PD) assessments. Saliva is a bodily fluid, which might be used as a source of biomarkers for PD. Our article has reviewed several publications on salivary proteins in PD patients and their potential as biomarkers. We find out that α-Syn’s proportion in oligomeric form is higher in PD patients’ saliva, which is potent to use as a biomarker for PD. The salivary concentration of DJ-1 and alpha-amylase is lower in PD patients. Also, substance P level is more moderate in PD patients. Although salivary flow rate is decreased in PD patients, high levels of heme oxygenase and acetylcholinesterase might be used as noninvasive biomarkers. Salivary miRNAs (miR-153, miR-223, miR-874, and miR-145-3p) are novel diagnostic biomarkers that should be given more attention