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Fungal vaccines, mechanism of actions and immunology: A comprehensive review
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Fungal infections include a wide range of opportunistic and invasive diseases. Two of four major fatal diseases in patients with human immunodeficiency virus (HIV) infection are related to the fungal infections, cryptococcosis, and pneumocystosis. Disseminated candidiasis and different clinical forms of aspergillosis annually impose expensive medical costs to governments and hospitalized patients and ultimately lead to high mortality rates. Therefore, urgent implementations are necessary to prevent the expansion of these diseases. Designing an effective vaccine is one of the most important approaches in this field. So far, numerous efforts have been carried out in developing an effective vaccine against fungal infections. Some of these challenges engaged in different stages of clinical trials but none of them could be approved by the United States Food and Drug Administration (FDA). Here, in addition to have a comprehensive overview on the data from studied vaccine programs, we will discuss the immunology response against fungal infections. Moreover, it will be attempted to clarify the underlying immune mechanisms of vaccines targeting different fungal infections that are crucial for designing an effective vaccination strategy
The effects of infant massage on maternal postpartum depression: A randomized controlled trial
Get PDFBackground:Maternal postpartum depression (PPD) is a common problem after childbirth. It is a risk factor for low-quality mother-infant interaction. Infant massage may help alleviate depressive disorders. Objectives:This study aimed to investigate the effects of infant massage by mothers on maternal PPD. Methods:This clinical trial was conducted on 120 primiparous mothers with PPD. Mothers were randomly recruited and allocated to a control and an intervention group. In the intervention group, mothers were instructed to give their infants 15-min massage twice daily for 6 consecutive weeks from the 3rd postnatal week onward. However, mothers in the control group did not receive such training. Before and after the intervention, PPD was assessed using the Edinburgh Postnatal Depression Scale. Data analysis was performed using the Chi-square test, independent-samples t-test, paired-samples t-test, Wilcoxon signed-rank test, and univariate and multivariable logistic regression. Results:Groups did not significantly differ from each other concerning parents' and infants' demographic characteristics (P > 0.05) and the pretest mean score of PPD (P= 0.46). However, the posttest mean score of depression in the intervention group was significantly lower than the control group (7.75 ± 2.18 vs. 9.2 ± 2.04; P < 0.001). In addition, the posttest relative frequency of PPD was significantly lower in the intervention group (15/60 25% vs. 26/60 43.3%; χ2 = 4.48; P = 0.034). After controlling the effects of other variables, the odds of PPD in the intervention group was 0.5 times (95% confidence interval: 0.2, 0.94) less than the control group (P= 0.003). Conclusion:Infant massage by mothers significantly alleviates maternal PPD. Health-care professionals, particularly midwives, are recommended to instruct mothers to provide infant massage in order to alleviate their own PPD
Fusobacterium nucleatum and colorectal cancer: A mechanistic overview
No full textColorectal cancer (CRC) is the third most prevalent cancer in the world. There are many risk factors involved in CRC. According to recent findings, the tumor microenvironment and feces samples of patients with CRC are enriched by Fusobacterium nucleatum. Thus, F. nucleatum is proposed as one of the risk factors in the initiation and progression of CRC. The most important mechanisms of Fusobacterium nucleatum involved in CRC carcinogenesis are immune modulation (such as increasing myeloid-derived suppressor cells and inhibitory receptors of natural killer cells), virulence factors (such as FadA and Fap2), microRNAs (such as miR-21), and bacteria metabolism. The aim of this review was to evaluate the mechanisms underlying the action of F. nucleatum in CRC. © 2018 Wiley Periodicals, Inc
Melatonin administration lowers biomarkers of oxidative stress and cardio-metabolic risk in type 2 diabetic patients with coronary heart disease: A randomized, double-blind, placebo-controlled trial
Get PDFBackground & aims: Melatonin may benefit diabetic people with coronary heart disease (CHD) through its beneficial effects on biomarkers of oxidative stress and cardio-metabolic risk. This investigation evaluated the effects of melatonin administration on metabolic status in diabetic patients with CHD. Methods: This randomized, double-blind, placebo-controlled trial was conducted and involved 60 diabetic patients with CHD. Subjects were randomly allocated into two groups to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 30) or placebo (n = 30) once a day for 12 weeks. Results: Compared with the placebo, melatonin supplementation resulted in significant increases in plasma glutathione (GSH) (+64.7 ± 105.7 vs. �11.1 ± 137.6 μmol/L, P = 0.02) and nitric oxide (NO) (+0.9 ± 4.7 vs. �3.3 ± 9.6 μmol/L, P = 0.03), and significant decreases in malondialdehyde (MDA) (�0.2 ± 0.3 vs. +0.1 ± 0.5 μmol/L, P = 0.007), protein carbonyl (PCO) (�0.12 ± 0.08 vs. +0.03 ± 0.07 mmol/mg protein, P < 0.001) and serum high sensitivity C-reactive protein (hs-CRP) levels (�1463.3 ± 2153.8 vs. +122.9 ± 1230.4 ng/mL, P = 0.001). In addition, taking melatonin, compared with the placebo, significantly reduced fasting plasma glucose (�29.4 ± 49.0 vs. �5.5 ± 32.4 mg/dL, P = 0.03), serum insulin concentrations (�2.2 ± 4.1 vs. +0.7 ± 4.2 μIU/mL, P = 0.008), homeostasis model of assessment-estimated insulin resistance (�1.0 ± 2.2 vs. +0.01 ± 1.6, P = 0.04), total-/HDL-cholesterol ratio (�0.18 ± 0.38 vs. +0.03 ± 0.35, P = 0.02) and systolic (�4.3 ± 9.6 vs. +1.0 ± 7.5 mmHg, P = 0.01) and diastolic blood pressure (�2.8 ± 7.3 vs. +0.1 ± 3.6 mmHg, P = 0.04). Melatonin treatment also significantly increased quantitative insulin sensitivity check index (+0.006 ± 0.01 vs. �0.004 ± 0.01, P = 0.01) and serum HDL-cholesterol (+2.6 ± 5.5 vs. �0.01 ± 4.4 mg/dL, P = 0.04). Supplementation with melatonin had no significant effect on other metabolic parameters. Conclusions: Overall, melatonin intake for 12 weeks to diabetic patients with CHD had beneficial effects on plasma GSH, NO, MDA, PCO, serum hs-CRP levels, glycemic control, HDL-cholesterol, total-/HDL-cholesterol ratio, blood pressures and parameters of mental health. Registered under ClinicalTrials.gov Identifier no. http://www.irct.ir: IRCT2017051333941N1. © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolis
Effect of cinnamon (Cinnamomum Zeylanicum) supplementation on serum C-reactive protein concentrations: A meta-analysis and systematic review
Get PDFObjective: The effect of cinnamon (Cinnamomum Zeylanicum) on serum C-reactive protein (CRP), an acute phase protein commonly used as a marker of inflammation, is uncertain. Therefore, the objective of the present study was to conduct a systematic review and meta-analysis of published randomised controlled trials (RCTs) of cinnamon to determine the effect on levels of serum CRP, relative to controls. Design: Studies were identified by a search of electronic databases including PubMed, Cochrane Library, Google Scholar and Scopus before August 2018. Combined and stratified analyses were used. Weighted mean differences (WMD) and its 95 confidence interval were estimated for net change in serum CRP by using random-effects model. The heterogeneity of meta-analysis was assessed by � 2 and I 2 test. Results: Six studies were identified, and data from 285 participants were included. Pooled analysis showed significant reductions in serum CRP (WMD: �0.81 mg/L, 95 CI: �1.36 to �0.26, p = 0.004), with significant heterogeneity between selected studies. Improvements in sub-group analysis were observed when baseline CRP levels were greater than 3 mg/dL, and in trials of >12 weeks duration. Doses <1500 mg/day and �1500 mg/day were effective in lowering serum CRP (WMD: �0.56 mg/dL, 95 CI: �1.01 to -0.10, p = 0.02 and WMD: �2.13 mg/dL, 95 CI: �4.08 to �0.19, p = 0.03), respectively, with significantly reduced heterogeneity in trials with lower doses of cinnamon <1500 mg/day (test for heterogeneity: P = 0.22 and I2 = 33). No changes were found in controls. Conclusion: Cinnamon supplementation improves levels of serum CRP, particularly in chronic conditions, where basal CRP levels are raised. Further well-designed studies are warranted to confirm or not the above-mentioned findings. © 2018 Elsevier Lt
Regulation of tumor angiogenesis by microRNAs: State of the art
No full textMicroRNAs (miRNAs, miRs) are small (21�25 nucleotides) endogenous and noncoding RNAs involved in many cellular processes such as apoptosis, development, proliferation, and differentiation via binding to the 3�-untranslated region of the target mRNA and inhibiting its translation. Angiogenesis is a hallmark of cancer, which provides oxygen and nutrition for tumor growth while removing deposits and wastes from the tumor microenvironment. There are many angiogenesis stimulators, among which vascular endothelial growth factor (VEGF) is the most well known. VEGF has three tyrosine kinase receptors, which, following VEGF binding, initiate proliferation, invasion, migration, and angiogenesis of endothelial cells in the tumor environment. One of the tumor microenvironment conditions that induce angiogenesis through increasing VEGF and its receptors expression is hypoxia. Several miRNAs have been identified that affect different targets in the tumor angiogenesis pathway. Most of these miRNAs affect VEGF and its tyrosine kinase receptors expression downstream of the hypoxia-inducible Factor 1 (HIF-1). This review focuses on tumor angiogenesis regulation by miRNAs and the mechanism underlying this regulation. © 2018 Wiley Periodicals, Inc
Assessment of microRNA-146a in generalized aggressive periodontitis and its association with disease severity
Get PDFBackground and Objective: MicroRNA-146a (miR-146a) is a small noncoding RNA that plays a critical role in the negative regulation of the innate immune response, and the dysregulation of miR-146a has been associated with several inflammatory disorders. In generalized aggressive periodontitis (GAgP) the degree of clinical inflammation appears to be similar to that of chronic periodontitis, and, in this situation, age of onset and family history are important additional criteria for diagnosis. This study was performed to evaluate the level of miR-146a expressed in gingival tissues of patients with GAgP and its association with disease severity. Material and Methods: Gingival samples from 18 patients with GAgP and 10 healthy subjects were collected and the level of miR-146a and its targets, including necrosis factor-alpha, interleukin-1beta, and interleukin-6, were assessed using real-time PCR. Clinical parameters, including probing depth and clinical attachment loss, were measured and their correlations with the level of miR-146a were determined. Results: Our results demonstrated an elevation in the level of miR-146a expressed in patients with GAgP compared with healthy controls (P <.001), which was directly associated with disease severity (P <.05). Overexpression of miR-146a was accompanied by a reduction in the levels of pro-inflammatory cytokines. Conclusions: Our findings suggest that there is an association between miR-146a and GAgP and imply that miR-146a may serve as an indicator of periodontal disease severity. However, further studies and additional information are required to confirm this relationship and the precise role of miR-146a in the development and/or progression of periodontitis. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Lt
N�89 and C�274 Truncated Enzymes of Chondroitinase ABC I Regain More Imperturbable Microenvironments Around Structural Components in Comparison to their Wild Type
Get PDFImmune response stimulation and inactivation of chondroitinase ABC I in physiological condition have been limited its use in various clinical conditions as a bacterial enzyme drug. In the present study, we have investigated some structural and functional features of N�89, C�274 and N�89C�274; three designed truncated cABC I, in order to clarify the unclear role of two terminal parts of cABC I i.e., the 1�89 and 747�1021 amino acids sequences of the full length enzyme through truncation. As a result, the numbers of potential epitopes, the susceptibility to trypsin digestion, ANS fluorescence spectra, and fluorescence quenching using KI and acrylamide were diminished for N�89 and C�274 in comparison to the wild type. Secondary and tertiary structure investigation for N�89 and C�274 revealed that the intrinsic fluorescence was increased and Far-UV CD spectra were changed accordingly. Relative to the wild type enzyme, 0.164, 0.195 remaining activity and lack of activity was shown with the zymographic assay for N�89, C�274 and N�89C�274 variants, respectively. The diminished enzyme activity and structural changes suggested a reorientation of microenvironments interactions including cation�� interactions around structural elements toward lowering regional mobility. Constructing applicable truncated cABC I with improved features could be regarded as a strategy to regain new possible functional advantages over the full length enzyme. © 2019, Springer Science+Business Media, LLC, part of Springer Nature
The effects of coenzyme Q10 supplementation on biomarkers of inflammation and oxidative stress in among coronary artery disease: a systematic review and meta-analysis of randomized controlled trials
Get PDFObjective: Systemic inflammation and oxidative stress significantly contribute in developing coronary artery disease (CAD). This systematic review and meta-analysis was aimed to determine the effects of coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress among patients with CAD. Methods: The electronic databases including MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library databases were systematically searched until Oct 2018. The quality assessment and heterogeneity of the selected randomized clinical Trials (RCTs) were examined using the Cochrane Collaboration risk of bias tool, and Q and I 2 tests, respectively. Given the presence of heterogeneity, random-effects model or fixed-effect model were used to pool standardized mean differences (SMDs) as summary effect sizes. Results: A total of 13 clinical RCTs of 912 potential citations were found to be eligible for the current meta-analysis. The pooled findings for biomarkers of inflammation and oxidative stress demonstrated that CoQ10 supplementation significantly increased superoxide dismutase (SOD) (SMD 2.63; 95 CI, 1.17, 4.09, P < 0.001; I 2 = 94.5) and catalase (CAT) levels (SMD 1.00; 95 CI, 0.57, 1.43, P < 0.001; I 2 = 24.5), and significantly reduced malondialdehyde (MDA) (SMD � 4.29; 95 CI � 6.72, � 1.86, P = 0.001; I 2 = 97.6) and diene levels (SMD � 2.40; 95 CI � 3.11, � 1.68, P < 0.001; I 2 = 72.6). We did not observe any significant effect of CoQ10 supplementation on C-reactive protein (CRP) (SMD � 0.62; 95 CI � 1.31, 0.08, P = 0.08; I 2 = 87.9), tumor necrosis factor alpha (TNF-α) (SMD 0.22; 95 CI � 1.07, 1.51, P = 0.73; I 2 = 89.7), interleukin-6 (IL-6) (SMD � 1.63; 95 CI � 3.43, 0.17, P = 0.07; I 2 = 95.2), and glutathione peroxidase (GPx) levels (SMD 0.14; 95 CI � 0.77, 1.04, P = 0.76; I 2 = 78.7). Conclusions: Overall, this meta-analysis demonstrated CoQ10 supplementation increased SOD and CAT, and decreased MDA and diene levels, but did not affect CRP, TNF-α, IL-6, and GPx levels among patients with CAD. © 2019, Springer Nature Switzerland AG
Effect of simulated mastication on the surface roughness and wear of machinable ceramics and opposing dental enamel
Get PDFObjective: Computer aided design-computer aided machining (CAD-CAM) ceramic crowns are replacing ceramo-metal ones due to newly developed mechanical properties and esthetics. To obtain knowledge about their interactions due to polishing and occlusal contacts with the opposing dental enamel specimen, including surface roughness and wear, the three-body wear simulation was investigated. Methods and Materials: The surface roughness (RA) and wear rate (mm) of four CAD-CAM blocks with different compositions including Vita Mark II, e.max, Suprinity, and Enamic, after two surface treatments of glazing and polishing, and their opposing enamel specimens, were investigated using a mastication simulator and atomic force microscope. Results: The roughness of all ceramic and to a greater extent enamel samples, with the exception of enamel opposing polished Enamic samples, was decreased after wear. No significant difference in wear was evident for the ceramic samples between the glazed and polished treatments. Lower wear rates were recorded only for polished Vita Mark II and polished Enamic in comparison to the glazed ones. Conclusion: The newly developed polishing systems for CAD-CAM ceramics can be good alternatives to reglazing, because the roughness and wear rate of both the ceramic and the opposing enamel will either not change or decrease. © Operative Dentistry, 2019