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Aims: This study examines microencapsulation as a method to enhance the stability of natural compounds, which typically suffer from inherent instability under environmental conditions, aiming to extend their application in the pharmaceutical industry., Methods: We explore and compare various microencapsulation techniques, including spray drying, freeze drying, and coacervation, with a focus on spray drying due to its noted advantages., Results: The analysis reveals that microencapsulation, especially via spray drying, significantly improves natural compounds' stability, offering varied morphologies, sizes, and efficiencies in encapsulation. These advancements facilitate controlled release, taste modification, protection from degradation, and extended shelf life of pharmaceutical products., Conclusion: Microencapsulation, particularly through spray drying, presents a viable solution to the instability of natural compounds, broadening their application in pharmaceuticals by enhancing protection and shelf life.

EFL listening comprehension has been a stark challenge for language learners, but little is known about the combined effect of individual differences, such as working memory capacity, and metacognitive intervention. Thus, the present experimental study investigates the effect of metacognitive intervention on the listening performance and metacognitive awareness of high- and low-WMC EFL learners. For this purpose, Oxford Placement Tests were distributed among 120 male Iranian EFL learners, of which 94 were identified as intermediate. Then, backward visual digit span tests were administered to measure their working memory capacity. Based on the median of all scores, 80 learners were selected and randomly assigned to two experimental groups and two control groups each with 20 participants. Next, their performance on the International English Language Testing System and the Metacognitive Awareness Listening Questionnaire was measured before and after the 8-session metacognitive intervention. Results showed that high-WMC experimental learners had a higher gain with a large effect size in terms of listening performance compared with all the other groups. In addition, the experimental group learners reported the significantly higher use of the metacognitive strategies with a moderate effect size. Interestingly, low-WMC learners' listening performance and metacognitive awareness also improved as a result of the intervention. Our findings bear pedagogical significance in that individual differences in WMC should be considered more in both EFL language classes and the future line of research involving the metacognitive intervention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To describe a patient diagnosed with Exophiala jeanselmei keratitis., Methods: We report a case of a patient who developed infectious keratitis following laser in situ keratomileusis and chronic topical steroid use for approximately six months in both eyes. An atypical infiltrate containing dark pigmentation was noted in the left eye on the initial presentation. During treatment, the infiltrates of the right eye began to exhibit a similar pigmentation., Results: Early treatment with topical antifungals was initiated in the left eye and later in the right eye once culture results returned. Both eyes recovered with good vision after approximately one month., Conclusions: Patients treated with postoperative topical corticosteroids should be cautioned of potential adverse effects of chronic use and have close follow-up. If infectious keratitis develops, particularly after two weeks, then atypical organisms, such as fungi, should be considered. In addition, our case highlights the significance of recognizing and associating dark-pigmentation with fungal etiologies., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Contact Lens Association of Ophthalmologists.)

Background: Today, modern lifestyles and disrupted sleep patterns cause circadian clock rhythm impairments that are associated with altered leptin levels, which subsequently affect a wide range of physiological processes and have significant health burdens on societies. Nevertheless, there has been no systematic review of circadian clock genes and proteins, leptin, and related signaling pathways., Methods: Accordingly, we systematically reviewed circadian clock proteins, leptin, and molecular mechanisms between them by searching Pubmed, Scopus, ProQuest, Web of Sciences, and Google Scholar until September 2022. After considering the inclusion and exclusion criteria, 20 animal studies were selected. The risk of bias was assessed in each study., Results: The results clarified the reciprocal interconnected relationship between circadian clock genes and leptin. Circadian clock genes regulate leptin expression and signaling via different mechanisms, such as CLOCK-BMAL1 heterodimers, which increase the expression of PPARs. PPARs induce the expression of C/EBPα, a key factor in upregulating leptin expression. CLOCK-BMAL1 also induces the expression of Per1 and Rev-erb genes. PER1 activates mTORC1 and mTORC1 enhances the expression of C/EBPα. In addition, REV-ERBs activate the leptin signaling pathway. Also, leptin controls the expression of circadian clock genes by triggering the AMPK and ERK/MAPK signaling pathways, which regulate the activity of PPARs. Moreover, the roles of these molecular mechanisms are elucidated in different physiological processes and organs., Conclusions: Crosstalk between circadian clock genes and leptin and their affecting elements should be considered in the selection of new therapeutic targets for related disorders, especially obesity and metabolic impairments., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

In order to help dentists in choosing the right type of cement for implant-based prostheses, the radiopacity of commonly used cements available in the market was investigated by digital radiography with PSP sensor. In the present study, temporary cements of TempBond (Kerr, Germany), TempBond clear (Kerr, Germany), Dycal (Dentsply, USA) and permanent cements of Multilink N (Ivoclar, Brazil), Panavia F 2.0 (Kurrary, Japan), Fuji plus (GC, Japan), RelyX (3M, USA), Durelon (3M, USA) were used. Four pill-like samples with 0.5 mm and 1 mm thickness and 5 mm in diameter inside the silicon index as recommended by the manufacturer were prepared for each cement. Aluminum step wedge (99% aluminum alloy) was used as control. Using digital radiography, cement and aluminum step wedge samples were radiographed. The images of cement tablets were measured by digital radiography using DFW software to check their radiopacity values. Bonferroni test and Mann-Whitney U test were used for comparison of cements. The highest radiopacity between the group of 1 and 0.5 mm thickness was related to Glass ionomer Fujiplus GC (2407±45.99) and TempBond (137.21±22.46) cement, respectively. Whereas, the lowest radiopacity among the groups was related to Clear cement. The difference between the mean radiopacities among the studied groups was statistically significant (p<0.001). Based on the results, among the available cements, Glass ionomer Fujiplus GC and TempBond cement are the most efficient for 1 and 0.5 mm thickness, respectively, and Clear cement is the least efficient cement in both groups in terms of radiopacity.

Purpose: To compare the efficacy of phakic intra-ocular lenses in isolation or in combination with corneal crosslinking (CXL) and/or intra-stromal corneal ring segments (ICRS) in keratoconus., Methods: Data extracted from the publications meeting the selection. The outcome parameters included mean pre- and post-operative uncorrected distance visual acuity, corrected distance visual acuity (CDVA), sphere and cylinder of refraction and complications. Available data analyzed with Cochrane Review Manager., Results: A total of 23 studies including 464 eyes were included. All the parameters showed significant improvement in all subgroups other than CDVA in ACPIOL + CXL subgroup and cylinder in PIOL + CXL subgroups. There was not a significant difference between PCPIOL and ACPIOL in the outcomes, exception was more improvement of CDVA in "ACPIOL only" than" PCPIOL only" subgroup., Conclusion: Both PCPIOLs and ACPIOLs are comparably safe and efficient options in management of KCN and their efficacy significantly improves when combined with CXL/ICRS., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: In the present study, we aimed to validate the Behçet's syndrome Overall Damage Index (BODI) and compare its performance with that of vasculitis damage index (VDI) in Iranian patients with BD., Methods: This study included 274 patients with a diagnosis of BD and median follow-up of 40 months. The medical records of the patients were reviewed and the demographic characteristics, disease activity status, clinical manifestations, and data on organs damage were collected from all patients., Results: To evaluate the construct/convergent validity, BODI and VDI were applied to all participants. We found a good correlation between BODI score and VDI score. There was a significant and strong correlation between physician global assessment with BODI (r = 0.869, P = 0.001) and VDI (r = 0.817, P = 0.001). The ability of BODI to determine the accumulation of damage over time was assessed by analyzing the changes in BODI score over time. The increase in BODI score was occurred in 53 (19.3%) patients. In comparison, the increase in VDI score occurred in 36 (13.1%) patients. The increase in median BODI was significantly more than median VDI (P < 0.001). Multiple linear regression analysis showed that age at disease onset, disease duration, and disease severity were independent predictors of BODI scores. Reliability of BODI was examined by comparing the BODI scores as determined by two independent assessors in 100 patients. Cronbach's α was 0.942., Conclusion: The BODI demonstrated acceptable validity and reliability in assessing BD-related damage in Iranian patients with BD., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Purpose: To describe a 25-year-old female patient with unilateral Roth spots as the initial presentation of Essential Thrombocythemia., Method: Case report., Results: A 25 -year-old female presented with visual complaints of seeing flashing lights and mild blurred vision in her left eye. Dilated fundus exam revealed intra-retinal hemorrhages with a pattern compatible with Roth spots. Further work up showed thrombocythemia with positive JAK2 (V617F) mutation, confirming the diagnosis of Essential Thrombocythemia (ET). The symptoms and fundus findings resolved in one month after initiation of the treatment with low dose oral aspirin.ET which is defined as repeated platelet count of ≥ 450,000 per microliter without a secondary cause, can present with highly variable symptoms from being asymptomatic to chest pain, cerebral venous sinus thrombosis, retinal vascular occlusion, and granuloma annulare.In the presented case Roth spots hastened the need for more complete workup to determine the systemic cause of this ocular finding, ultimately leading to the diagnosis., Conclusion: Finding of Roth spots may warrant a systemic work up to find out the underlying pathologic condition, which in the present case was Essential Thrombocythemia, a potentially life-threatening condition., Declaration: Authors declare no conflict of interest., Competing Interests: Authors declare no conflict of interest.

Background: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs., Result: There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials., Conclusion: This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19., (© 2023. The Author(s).)

Objective: New coronavirus (COVID-19) pandemic socioeconomically affected the world. In this study, we measured the perceived stress in response to the COVID-19 pandemic among Iranians to determine the groups at both extremes of the spectrum followed by identifying the stressors and coping mechanisms., Methods: This study was a mixed-methods study. We distributed a web-based 10-item perceived stress scale (PSS-10), to measure perceived stress score (PSS), through social networks from March 12 to 23, 2020. Then, we interviewed 42 students, 31 homemakers, 27 healthcare providers, and 21 male participants to identify the sources of stress and coping mechanisms., Results: Finally, 13,454 participants completed the questionnaires. The median and interquartile range (IQR) of the participants' PSS was 21 (15-25). Students, homemakers, and healthcare workers (HCWs) showed a higher median (IQR) of PSS compared to other groups (23 [18 to 27], 22 [16 to 26], and 19 [14 to 24], respectively). Male participants showed a lower median (IQR) PSS (17 [12 to 23]). Content analysis of 121 participants' answers showed that the most common stressors were school-related issues mentioned by students, family-related issues mentioned by homemakers, and COVID-19-related issues mentioned by healthcare providers. Male participants' coping mechanisms were mostly related to the perception of their abilities to cope with the current crisis., Conclusion: Our participants clinically showed a moderate level of PSS. The main stressors among students, homemakers, and HCWs were related to their principal role in this period, and male participants' coping mechanisms were inspired by the self-image retrieved from the social perspectives.

Mounting scientific evidence over decades has established that atherosclerosis is a chronic inflammatory disorder. Among the potentially critical sources of vascular inflammation during atherosclerosis are the components of pathogenic bacteria, especially lipopolysaccharide (LPS). Toll-like receptor (TLR)-4, expressed on different inflammatory cells involved with the recognition of bacterial LPS, has been recognized to have mutations that are prevalent in a number of ethnic groups. Such mutations have been associated with a decreased risk of atherosclerosis. In addition, epidemiological investigations have proposed that LPS confers a risk factor for the development of atherosclerosis. Gram-negative bacteria are the major source of LPS in an individual's serum, which may be generated during subclinical infections. The major cell receptors on inflammatory cells involved in the pathogenesis of atherosclerosis, like macrophages, monocytes, and dendritic cells (DCs), are CD14, MD-2, and LPS binding protein (LBP). These receptors have been blamed for the development of atherosclerosis through dysregulated activation following LPS recognition. Lipoproteins may also play a role in modulating the LPS-induced inflammatory events during atherosclerosis development. In this review article, we attempt to clarify the role of LPS in the initiation and progression of atherosclerotic lesion development., (Copyright © 2021. Published by Elsevier Inc.)

Background: COVID-19 related stigma has been identified as a critical issue since the beginning of the pandemic. We developed a valid and reliable questionnaire to measure COVID-19 related enacted stigma, inflicted by the non-infected general population. We applied the questionnaire to measure COVID-19 related enacted stigma among Tehran citizens from 27 to 30 September 2020., Methods: A preliminary questionnaire with 18 items was developed. The total score ranged from 18 to 54; a higher score indicated a higher level of COVID-19 related stigma. An expert panel assessed the face and content validity. Of 1637 randomly recruited Tehran citizens without a history of COVID-19 infection, 1064 participants consented and were interviewed by trained interviewers by phone., Results: Item content validity index (I-CVI), Item content validity ratio (I-CVR), and Item face validity index (I-FVI) were higher than 0.78 for all 18 items. The content and face validity were established with a scale content validity index (S-CVI) of 0.90 and a scale face validity index (S-CVI) of 93.9%, respectively. Internal consistency of the questionnaire with 18 items was confirmed with Cronbach's alpha of 0.625. Exploratory factor analysis revealed five latent variables, including "blaming", "social discrimination", "dishonor label", "interpersonal contact", and "retribution and requital attitude". The median of the stigma score was 24 [25th percentile: 22, 75 the percentile: 28]. A large majority (86.8%) of participants reported a low level of stigma with a score below 31. None of the participants showed a high level of stigma with a score above 43. We found that the higher the educational level the lower the participant's stigma score., Conclusion: We found a low level of stigmatizing thoughts and behavior among the non-infected general population in Tehran, which may be due to the social desirability effect, to the widespread nature of COVID-19, or to the adaptation to sociocultural diversity of the large city., (© 2022. The Author(s).)

Cell therapeutic approaches focusing on the regeneration of damaged tissue have been a popular topic among researchers in recent years. In particular, self-repair scarring from the central nervous system (CNS) can significantly complicate the treatment of an injured patient. In CNS regeneration schemes, either glial progenitor cells or reactive glial cells have key roles to play. In this review, the contribution and underlying mechanisms of these progenitor/reactive glial cells during CNS regeneration are discussed, as well as their role in CNS-related diseases., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The quality of health care has a significant impact on both patients and the health system in terms of long-term costs and health consequences. This study focuses on determining the long-term cost-effectiveness in quality of diabetes care in two different settings (private/public) using longitudinal patient-level data in Iran., Methods: By extracting patients intermediate biomedical markers in under-treatment type 2 diabetes patients(T2DP) in a longitudinal retrospective study and by applying the localized UKPDS diabetes model, lifetime health outcomes including life expectancy, quality-adjusted Life expectancy (QALE) and direct medical costs of managing disease and related complications from a healthcare system perspective was predicted. Costs and utility decrements had derived on under-treatment T2DP from 7 private and 8 Public diabetes centers. We applied two steps sampling mehods to recruit the needed sample size (cluster and random sampling). To cope with first and second-order uncertainty, we used Monte-Carlo simulation and bootstrapping techniques. Both cost and utility variables were discounted by 3% in the base model., Results: In a 20-year time horizon, according to over 5 years of quality of care data, outcomes-driven in the private sector will be more effective and more costly (5.17 vs. 4.95 QALE and 15,385 vs. 8092). The incremental cost-effectiveness ratio (ICER) was $33,148.02 per QALE gained, which was higher than the national threshold., Conclusion: Although quality of care in private diabetes centers resulted in a slight increase in the life expectancy in T2DM patients, it is associated with unfavorable costs, too. Private-sector in management of T2DM patients, compared with public (governmental) diabetic Centers, is unlikely to be cost-effective in Iran., (© 2022. The Author(s).)

Psoriasis is an organ-specific autoimmune disease characterized by the aberrant proliferation and differentiation of keratinocytes, leading to skin lesions. Abnormal immune responses mediated by T cells and dendritic cells and increased production of inflammatory cytokines have been suggested as underlying mechanisms in the pathogenesis of psoriasis. Emerging evidence suggests that there is a heritable basis for psoriatic disorders. Moreover, numerous gene variations have been associated with the disease risk, particularly those in innate and adaptive immune responses and antigen presentation pathways. Herein, this article discusses the genetic implications of psoriatic diseases' etiopathogenesis to develop novel investigative and management options., (© 2022 Bentham Science Publishers.)

Background: Non-communicable diseases are imposing a considerable burden on Iran. This study aims to assess the Return on Investment (ROI) for implementation of Non-communicable diseases (NCDs) prevention program in Iran., Methods: Four disease groups including cardiovascular diseases, diabetes, cancer, and respiratory diseases were included in our ROI analysis. The study followed four steps: 1) Estimating the total economic burden of NCDs using the Cost-of-Illness approach. 2) Estimating the total costs of implementing clinical and preventive interventions using an ingredient based costing at delivering level and a program costing method at central level.3) Calculating health impacts and economic benefits of interventions using the impact measures of avoided incidence, avoided mortality, healthy life years (HLYs) gained, and avoided direct treatment costs. 4) Calculating the ROI for each intervention in 5- and 15- year time horizons., Results: The total economic burden of NCDs to the Iranian economy was IRR 838.49 trillion per year (2018), which was equivalent to 5% of the country's annual Gross Domestic Product (GDP). The package of NCD will lead to 549 000 deaths averted and 2 370 000 healthy life years gained over 15 years, and, financially, Iranian economy will gain IRR 542.22 trillion over 15 years. The highest ROI was observed for the package of physical activity interventions, followed by the interventions addressing salt, tobacco package and clinical interventions. Conclusions NCDs in Iran are causing a surge in health care costs and are contributing to reduced productivity. Those actions to prevent NCDs in Iran, as well as yielding to a notable health impact, are giving a good economic return to the society. This study underscores an essential need for establishment of a national multi-sectorial NCD coordination mechanism to bring together and strengthen existing cross-agency initiatives on NCDs., (© 2022. The Author(s).)

Background: There are increasing concerns about mental health consequences of the COVID-19 pandemic among seafarers. This study aims to assess the effects of the current global health pandemic on life satisfaction and adverse psychological outcomes among seafarers., Methods: In this cross-sectional study, 470 multinational seafarers working on board ships of two international shipping companies were assessed. Mental health outcomes were assessed by the general anxiety disorder (GAD-7) questionnaire, post-traumatic stress disorder (PTSD-8) questionnaire, and patient health questionnaire (PHQ-9) depressive severity score. Multivariate logistic regression was used to determine the association of demographic and work-related variables with mental health outcomes., Results: Overall, 439 out of 470 invited seafarers with a mean age of 34.5 (SD: 8.05) years participated in this study (participation rate: 93.4%). The prevalence of anxiety, depressive, and post-traumatic stress symptoms was 12.4, 14.1, and 37.3%, respectively. In the multivariate model, the current vessel's signing duration was directly associated with the odds of depressive and intrusion symptoms. Moreover, the duration of work per week was inversely associated with hyper-vigilance and avoidance. Also, non-officers, compared to officers, experienced significantly lower anxiety and depressive symptoms, hyper-vigilance, and avoidance., Conclusion: The present study revealed a high prevalence of mental health problems among seafarers during the COVID-19 pandemic. We recommend that more evidence is generated regarding psychosocial health issues for this vulnerable occupation., (© 2022. The Author(s).)

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings., (© 2021 John Wiley & Sons Ltd.)

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day., (© 2021 John Wiley & Sons Ltd.)

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are administered as first line therapy for hypercholesterolemia, both in primary and secondary prevention. There is a growing body of evidence showing that beyond their lipid-lowering effect, statins have a number of additional beneficial properties. Pitavastatin is a unique lipophilic statin with a strong effect on lowering plasma total cholesterol and triacylglycerol. It has been reported to have pleiotropic effects such as decreasing inflammation and oxidative stress, regulating angiogenesis and osteogenesis, improving endothelial function and arterial stiffness, and reducing tumor progression. Based on the available studies considering the risk of statin-associated muscle symptoms it seems to be also the safest statin. The unique lipid and non-lipid effects of pitavastatin make this molecule a particularly interesting option for the management of different human diseases. In this review, we first summarized the lipid effects of pitavastatin and then strive to unravel the diverse pleiotropic effects of this molecule., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Statins are well-known lipid-lowering drugs. The pleiotropic effects of statins have brought about some beneficial effects on improving the therapeutic outcomes of cell therapy and tissue engineering approaches. In this review, the impact of statins on mesenchymal stem cell behaviors including differentiation, apoptosis, proliferation, migration, and angiogenesis, as well as molecular pathways which are responsible for such phenomena, are discussed. A better understanding of pathways and mechanisms of statin-mediated effects on mesenchymal stem cells will pave the way for the expansion of statin applications. Furthermore, since designing a suitable carrier for statins is required to maintain a sufficient dose of active statins at the desired site of the body, different systems for local delivery of statins are also reviewed., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Considering the pathologic significance of inflammation and oxidative stress in rheumatoid arthritis (RA) as well as the antioxidant, anti-inflammatory and hypolipidemic effects of melatonin, the current research is designed to investigate the effect of melatonin supplementation on disease activity, oxidative stress, inflammatory, and metabolic parameters in RA patients., Methods: In this randomized double-blind, placebo-controlled trial, 64 RA cases were selected and randomly assigned into 2 groups to take 6 mg/day melatonin or placebo for 12 weeks. Before and after trial, serum malondialdehyde (MDA), total antioxidant capacity (TAC), erythrocyte sedimentation rate (ESR), lipid profile, fasting blood sugar (FBS), and insulin levels were measured and disease activity was determined by disease activity score-28 (DAS-28)., Results: Compared to the baseline, melatonin significantly decreased DAS-28, ESR, MDA, and LDL-C by 50.5%, 59%, 97%, and 13%, respectively (P<0.001) and significantly increased TAC by 89% (P=0.013) and HDL-C by 22% (P<0.001). After treatment, considerable differences were only seen between the two groups in serum MDA (P<0.001) and LDL-C (P=0.007) concentrations, adjusted for baseline measures. Moreover, there were no significant changes in DAS-28, ESR, TAC, triglyceride, total cholesterol, HDL-C, FBS, and insulin levels compared to placebo group (P>0.05)., Conclusions: Although melatonin supplementation had no beneficial effects on DAS-28, it could lower serum MDA and LDL-C levels. It seems that melatonin supplementation should not be used as a replace for routine drugs prescribed in RA treatment. Further investigations should be conducted to fully understand the effects of melatonin in RA. Key Points • Compared to baseline, melatonin significantly decreased DAS-28, ESR, MDA, and LDL-C and significantly increased TAC and HDL-C. • After treatment, considerable differences were only seen between melatonin and placebo groups in serum MDA and LDL-C concentrations. • After treatment, there were no significant changes in DAS-28, ESR, TAC, triglyceride, total cholesterol, HDL-C, FBS, and insulin levels compared to the placebo group., (© 2021. International League of Associations for Rheumatology (ILAR).)

Statins, which are functionally known as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) inhibitors, are lipid-lowering compounds widely prescribed in patients with cardiovascular diseases (CVD). Several biological and therapeutic functions have been attributed to statins, including neuroprotection, antioxidation, anti-inflammation, and anticancer effects. Pharmacological characteristics of statins have been attributed to their involvement in the modulation of several cellular signaling pathways. Over the past few years, the therapeutic role of statins has partially been attributed to the induction of autophagy, which is critical in maintaining cellular homeostasis and accounts for the removal of unfavorable cells or specific organelles within cells. Dysregulated mechanisms of the autophagy pathway have been attributed to the etiopathogenesis of various disorders, including neurodegenerative disorders, malignancies, infections, and even aging. Autophagy functions as a double-edged sword during tumor metastasis. On the one hand, it plays a role in inhibiting metastasis through restricting necrosis of tumor cells, suppressing the infiltration of the inflammatory cell to the tumor niche, and generating the release of mediators that induce potent immune responses against tumor cells. On the other hand, autophagy has also been associated with promoting tumor metastasis. Several anticancer medications which are aimed at inducing autophagy in the tumor cells are related to statins. This review article discusses the implications of statins in the induction of autophagy and, hence, the treatment of various disorders., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Armita Mahdavi Gorabi et al.)

Statins, a class of drugs for lowering serum LDL-cholesterol, have attracted attention because of their wide range of pleiotropic effects. An important but often neglected effect of statins is their role in the renin-angiotensin system (RAS) pathway. This pathway plays an integral role in the progression of several diseases including hypertension, heart failure, and renal disease. In this paper, the role of statins in the blockade of different components of this pathway and the underlying mechanisms are reviewed and new therapeutic possibilities of statins are suggested.

Background: Our previous studies showed the safe preventive and therapeutic effects of immunization using the nanoliposomal antiPCSK9 vaccine called "Liposomal Immunogenic Fused PCSK9-Tetanus plus Alum adjuvant" (L-IFPTA), in mouse models of atherosclerosis. Here we aimed to ascertain the immunogenicity and safety of the L-IFPTA vaccine in a pre-clinical study in healthy non-human primates., Methods: Five male rhesus macaque monkeys were subcutaneously immunized with the L-IFPTA vaccine, four times with bi-weekly intervals. To evaluate immunogenicity, the plasma antiPCSK9 antibody in immunized monkeys was detected and quantified using the ELISA method. The functionality of the induced antiPCSK9 antibodies was determined by the PCSK9/LDLR in vitro binding assay kit. The safety of the vaccine was tested using the evaluation of several major circulating indicators including plasma lipid alterations, inflammatory biomarkers and organ injury biomarkers., Results: The resultant data indicated that the L-IFPTA vaccine significantly and highly induced the generation of functional and safe antiPCSK9 antibodies in immunized monkeys. Plasma levels of specific biomarkers indicating organ performance including creatinine, urea, uric acid, bilirubin, ALP, AS, ALT and TSH were not significantly altered. After immunization in healthy monkeys, non-prespecified endpoints (plasma levels of TC, LDL-C, VLDL-C and TG) were non-significantly reduced by 11.6 ± 36%; 16 ± 28%; 22 ± 53% and 24 ± 51%, respectively, while HDL-C was slightly increased by 2 ± 64%. There were also no significant changes in plasma levels of pro- and anti-inflammatory biomarkers., Conclusion: The L-IFPTA vaccine could efficiently stimulate the host humoral immune response to produce active antibodies that inhibit plasma PCSK9 while not provoking systemic inflammation and not adversely affecting organ performance.

It has been suggested that curcumin has the potential for lowering inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin/turmeric supplementation in reducing concentrations of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in patients with an inflammatory background. The main databases were searched to identify eligible trials evaluating the effect of curcumin in reducing IL-1, IL-6, IL-8, and TNF-α in serum up to March 2021. The effect sizes for weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Overall, 32 randomized controlled trials (RCTs) were included. There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment. Nonetheless, curcumin/turmeric supplementation was non-significantly associated with reduced levels of IL-6 (WMD = -0.33 pg/ml, 95% CI = -0.99-0.34, P = 0.33) and increased levels of IL-8 (WMD = 0.52 pg/ml, 95% CI = -1.13-2.17, P = 0.53). The dose-responses analysis indicated that curcumin/turmeric supplementation resulted in IL-1 and IL-8 alteration in a non-linear model. Subgroup analysis according to duration and dose of treatment and target population revealed diverse outcomes. Curcumin could have a beneficial effect in reducing the proinflammatory cytokines IL-1 and TNF-α, but not IL-6 and IL-8 levels., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Endothelial cells are a clinically important infection site for COVID-19, both as a mechanism for disease pathogenesis and as a therapeutic target. People with dysfunctional endothelium, defined by nitric oxide deficiency, appear to have a more severe disease course. As such, nitric oxide has therapeutic potential to mitigate COVID-19 severity. Inhaled nitric oxide appears to improve outcomes, although this strategy neglects systemic endothelium. Meanwhile, early studies have documented that endothelial protective medications, such as the administration of statins and ACE-inhibitors, are associated with less severe disease and reduced mortality. Importantly, these medications augment endothelial sources of nitric oxide, which may explain this effect.

Neuroglobin is the third member of the globin family to be identified in 2000 in neurons of both human and mouse nervous systems. Neuroglobin is an oxygen-binding globin found in neurons within the central nervous system as well as in peripheral neurons, that produces a protective effect against hypoxic/ischemic damage induced by promoting oxygen availability within the mitochondria. Numerous investigations have demonstrated that impaired neuroglobin functioning is implicated in the pathogenesis of multiple neurodegenerative disorders. Several in vitro and animal studies have reported the potential of neuroglobin upregulation in improving the neuroprotection through modulation of mitochondrial functions, such as ATP production, clearing reactive oxygen species (ROS), promoting the dynamics of mitochondria, and controlling apoptosis. Neuroglobin acts as a stress-inducible globin, which has been associated hypoxic/ischemic insults where it acts to protect the heart and brain, providing a wide range of applicability in the treatment of human disorders. This review article discusses normal physiological functions of neuroglobin in mitochondria-associated pathways, as well as outlining how dysregulation of neuroglobin is associated with the pathogenesis of neurodegenerative disorders., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Palindromic rheumatism (PR) is characterized by repetitive, afebrile episodes of acute arthritis and peri-arthritis. The aim of this study was considering the long-term outcomes of patients with PR who were treated with tight control strategy using Disease-modifying anti-rheumatic drugs (DMARDs)., Methods: We reviewed the charts of 106 patients diagnosed with PR who were referred to the Connective Tissue Diseases Research Center (CTDRC). We recruited all the patients diagnosed with PR according to the criteria of Hannonen. They visited the CTDRC clinic regularly and were treated with hydroxychloroquine and low dose prednisolone because of active episodes of PR. In cases that the attacks did not come under control in 3-6 months, methotrexate was added or replaced and the dose was increased up to 25mg/week. In resistant cases, sulfasalazine was added, followed by the addition of leflunomide and then azathioprine. Disease outcome was evaluated by getting complete or partial remission and prevention of disease evolution to rheumatoid arthritis (RA) or other inflammatory connective tissue diseases., Results: This study included 92 patients with PR who were treated with DMARDs. Attacks were controlled completely or partially in 76 (82.6%) patients. Medications free remission was obtained in 16.3% of the patients. RA developed in 8.7% of the patients. By multivariate logistic regression analysis, age ≤40 at disease presentation, non-adherence to therapy and PIP joints involvement were the only factors which independently predicted the risk of treatment failure., Conclusions: Tight control strategy by using DMARDs may control PR and prevent disease progression to RA., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: Keratoconus is a bilateral progressive noninflammatory degenerative disease of the cornea characterized by corneal thinning, irregular astigmatism, and subsequent visual impairment. It has an aggressive course in children. This systematic review evaluates the efficacy of available corneal collagen cross-linking (CXL) protocols for stabilizing the cornea in pediatric patients with keratoconus., Methods: We searched all peer-reviewed publications from 2000 to 2019 indexed in PubMed, Google Scholars, Web of Science, and Cochrane's Database for the terms keratoconus and cross-linking. The following data were extracted from eligible studies: study design, type of intervention, number of the eyes and mean age of patients for each study, duration of follow-up period, mean pre- and postoperative uncorrected and corrected visual acuity, keratometric and aberrometric indices, were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t tests., Results: A total of 28 studies, including 1,300 eyes, were reviewed. In conventional and accelerated epithelium-off techniques, there was a significant improvement in uncorrected and corrected visual acuities. Similarly, the keratometric indices improved significantly after CXL. Uncorrected visual acuity did not alter after CXL using transepithelial method., Conclusions: Both conventional and accelerated collagen CXL of the cornea are effective therapeutic options in management of keratoconus in children., (Published by Elsevier Inc.)

The identification of RNA interference (RNAi) has caused a growing interest in harnessing its potential in the treatment of different diseases. Modulation of dysregulated genes through targeting by RNAi represents a potential approach with which to alter the biological pathways at a post-transcriptional level, especially as it pertains to autoimmunity and malignancy. Short hairpin RNAs (shRNA), short interfering RNAs (siRNA), and microRNAs (miRNA) are mainly involved as effector mechanisms in the targeting of RNAi biological pathways. The manipulation and delivery of these molecules in an efficient way promotes the specificity and stability of RNAi-based systems, while minimizing the unwanted adverse reactions by the immune system and reducing cytotoxicity and off-target effects. Advances made to date in identifying the etiopathogenesis of autoimmune diseases has prompted the utilization of RNAi-based systems in vitro and in vivo. Future investigations aimed at deciphering the molecular basis of RNAi and optimizing the delivery of RNAi-based targeting systems will hopefully promote the applicability of such regulatory mechanisms and, ultimately, transfer the acquired knowledge from bench-to-bedside to ameliorate human diseases. In this review, we seek to clarify the potential of RNAi, with a focus on siRNAs, in designing therapeutics for potential treatment of human autoimmune disorders., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the pattern of retinal thickness distribution in patients with keratoconus (KCN) and its correlation with disease severity., Methods: For this cross-sectional cohort study, the study subjects with documented keratoconus and normal eyes were prospectively enrolled. All subjects had anterior segment (Pentacam HR) and posterior segment (Spectralis) imaging. Posterior segment imaging by optical coherence tomography included the posterior pole asymmetry analysis map. Data were analyzed with multiple linear regression models and correlation tests to examine the mean and variance of the measured thickness of the retina and its distribution relative to the presence and severity of KCN., Results: A total of 24 subjects with keratoconus (48 eyes) and 14 normal subjects (28 eyes) enrolled in this study. The posterior pole retinal thickness, both superior and inferior hemifields, as well as the overall retinal thickness in KCN patients was greater than the control group. There was a direct correlation between the overall retinal thickness of the posterior pole and the severity of KCN (R 2  = 0.422, P < 0.001). However, the variability of the retinal thickness showed no difference between KCN-afflicted and healthy eyes., Conclusion: Although KCN is a disease of the anterior segment of the eye, we found an orderly increase in posterior pole retinal thickness that is correlated with the severity of disease in KCN eyes compared to control. These findings suggest that the retina may maintain some degree of plasticity to respond to the degraded optical system of the eye.

Background: Altered innate immune function plays an important role in the initiation of inflammatory response in Behcet's disease (BD). Toll-like receptors (TLRs) are the master regulators of the innate immune system. Because the role of TLRs remains unknown in the pathogenesis of BD, the present study aimed to evaluate the expression levels and methylation status of the TLR2 and TLR4 promoters in patients with BD., Methods: In the present study, Iranian Azeri BD patients (n = 47) with an active (n = 22) and inactive (n = 25) period, and healthy controls (n = 61), were matched according to age, sex and ethnicity. TLR2 and TLR4 genes promoter CpG islands were predicted with the Eukaryotic Promoter Database (https://epd.vital-it.ch). Methylated DNA immunoprecipitation (MeDIP) was conducted., Results: The results showed that mRNA of TLR4 was significantly increased in the peripheral blood mononuclear cells (PBMCs) of BD patients with an active phase compared to the control group. Differences in mRNA of TLR4 between the inactive BD and control groups were not significant. Differences in TLR2 mRNA levels in the PBMCs of the active and inactive phase BD and control groups were not significant. The methylation rate of TLR4 gene promoter was significantly lower in the active and inactive BD groups compared to the control group. The difference between the active and inactive BD groups was not significant. There was no significant difference in the methylation rates of the TLR2 gene between studied groups., Conclusions: Our preliminary findings suggest that the hypomethylation of TLR4 gene may be involved in the pathogenesis of BD via increasing TLR4 expression., (© 2020 John Wiley & Sons, Ltd.)

Cardiac fibrosis stems from the changes in the expression of fibrotic genes in cardiac fibroblasts (CFs) in response to the tissue damage induced by various cardiovascular diseases (CVDs) leading to their transformation into active myofibroblasts, which produce high amounts of extracellular matrix (ECM) proteins leading, in turn, to excessive deposition of ECM in cardiac tissue. The excessive accumulation of ECM elements causes heart stiffness, tissue scarring, electrical conduction disruption and finally cardiac dysfunction and heart failure. Curcumin (Cur; also known as diferuloylmethane) is a polyphenol compound extracted from rhizomes of Curcuma longa with an influence on an extensive spectrum of biological phenomena including cell proliferation, differentiation, inflammation, pathogenesis, chemoprevention, apoptosis, angiogenesis and cardiac pathological changes. Cumulative evidence has suggested a beneficial role for Cur in improving disrupted cardiac function developed by cardiac fibrosis by establishing a balance between degradation and synthesis of ECM components. There are various molecular mechanisms contributing to the development of cardiac fibrosis. We presented a review of Cur effects on cardiac fibrosis and the discovered underlying mechanisms by them Cur interact to establish its cardio-protective effects.

Coronary artery diseases (CAD), as a leading cause of mortality around the world, has attracted the researchers' attention for years to find out its underlying mechanisms and causes. Among the various key players in the pathogenesis of CAD cytokines, microRNAs (miRNAs) are crucial. In this study, besides providing a comprehensive overview of the involvement of cytokines, growth factors, and miRNAs in CAD, the interplay between miRNA with cytokine or growth factors during the development of CAD is discussed., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2020 Armita Mahdavi Gorabi et al.)

Atherosclerosis is a disease in which lipid-laden plaques are developed inside the vessel walls of arteries. The immune system is activated, resulting in inflammation and oxidative stress. Endothelial cells (ECs) are activated, arterial smooth muscle cells (SMCs) proliferate, macrophages are activated, and foam cells are developed, leading to dysfunctional ECs. Epigenetic regulatory mechanisms, including DNA methylation, histone modifications, and microRNAs are involved in the modulation of genes that play distinct roles in several aspects of cell biology and physiology, hence linking environmental stimuli to gene regulation. Recent research has investigated the involvement of DNA methylation in the etiopathogenesis of atherosclerosis, and several studies have documented the role of this mechanism in various aspects of the disease. Regulation of DNA methylation plays a critical role in the integrity of ECs, SMC proliferation and formation of atherosclerotic lesions. In this review, we seek to clarify the role of DNA methylation in the development of atherosclerosis through different mechanisms., Competing Interests: Declaration of competing interest Dr. Penson owns four shares in Astra Zeneca PLC and has received travel/speaker's fees from Amgen Inc. Dr. Banach has served as speakers bureau: Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Sanofi-Aventis and Valeant; consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Lilly, MSD, Resverlogix, Sanofi-Aventis; received grants from Sanofi and Valeant. Other authors have no competing interests to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Autoimmune disorders are outcomes of impaired activity of the immune system regarding the maintenance of tolerance, which results in tissue damage secondary to an excess in the inflammatory response. Under normal conditions, the cells in the adaptive immune system are highly controlled to remain unresponsive against self-antigens (self-Ags) through various mechanisms and during different stages of maturation. CD69 (cluster of differentiation 69), a C-type lectin disulfide-linked homodimer, is expressed on different leukocytes, including newly-activated lymphocytes, certain subtypes of memory T-cells, infiltrating lymphocytes isolated from patients with chronic inflammatory disorders, and regulatory T-cells (Tregs). Cumulative evidence from in vitro and in vivo studies has revealed an immunoregulatory role for CD69. This marker has been reported to play a controversial role in chronic human inflammatory disorders. Many investigations have linked the absence of CD69 with a predisposition to inflammatory and/or autoimmune conditions, which indicates an immunoregulatory function for CD69 by mechanisms such as controlling the balance between differentiation of Th/Treg cells and enhancing the suppressive activity of Tregs. However, some reports from human studies have indicated that CD69 may exert a stimulatory effect on the inflammatory response. In this review, we first present a brief summary of the concept of 'immune tolerance' and, subsequently, review previous studies to uncover the details that underlie the immunoregulatory effects of CD69., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD - 0.66, 95% CI - 1.27, - 0.06), very-low-density lipoprotein (SMD - 1.59, 95% CI - 2.86, - 0.31), and total cholesterol (SMD - 0.65, 95% CI - 1.15, - 0.15). Similarly, zinc supplementation significantly decreased fasting blood glucose (SMD - 0.52, 95% CI - 0.96, - 0.07) and HbA1c (SMD - 0.64, 95% CI - 1.27, - 0.02). The effects of zinc supplementation on blood pressure and anthropometric indices were not statistically significant (P > 0.05). Zinc supplements had beneficial effects on glycemic indices and lipid profile. Thus, it appeared that zinc supplementation might be associated with a decrease in cardiometabolic risk factors contributing to a reduction in risk of atherosclerosis.

Background: Childhood hypertension is a predictor of later diseases, increases the risk for cardiovascular morbidity and mortality in adulthood and results in major economic burdens. The purpose of this study was to investigate the direct and indirect effect of anthropometric, socioeconomic and lifestyle factors on blood pressure (BP) in a large population-based sample of children and adolescents using a path analysis., Methods: This multi-centric nationwide study was performed on students aged 7-18 years. Anthropometric indices and blood pressure were measured by standard methods and demographic data, socioeconomic status, dietary habits and health related behaviors were obtained using validated questionnaires. Path analysis was applied to evaluate the relationships among the study variables and to implement the subsequent structural modeling., Results: Totally, 7235 students (50.6% boys; the mean age 12.3 ± 3.1 years) were assessed. Systolic and diastolic BP positively correlated with age (r = 0.35 and 0.26; respectively), BMI (r = 0.06 and 0.04; respectively) and WC (r = 0.05 and 0.03; respectively). According to path analysis, age had significant direct effect on BMI, WC, and BP (β = 0.035, 0.043 and 0.345; respectively), which was greater for BP. BMI and WC had the greatest direct effect on BP (β = 0.05 and 0.03; respectively). Education level, subjective health complaints, health-related behaviors and dietary habits had positive direct effects on BP (β = 0.036, 0.030, 0.018 and 0.017; respectively). Socioeconomic status and positive changes in diet had negative indirect effect on BP (β = - 0.001 for both)., Conclusion: Our findings strengthen the importance of weight and body composition in BP control. It is suggested to improve diet and health related behaviors especially in families with low socioeconomic position.

The consequences of atherosclerotic cardiovascular disease (ASCVD) include myocardial infarction, ischemic stroke, and angina pectoris, which are major causes of mortality and morbidity worldwide. Despite current therapeutic strategies to reduce risk, patients still experience the consequences of ASCVD. Consequently, a current goal is to enhance visualization of early atherosclerotic lesions to improve residual ASCVD risk. The uses of liposomes, in the context of ASCVD, can include as contrast agents for imaging techniques, as well as for the delivery of antiatherosclerotic drugs, genes, and cells to established sites of plaque. Additionally, liposomes have a role as vaccine adjuvants against mediators of atherosclerosis. Here. we review the scientific and clinical evidence relating to the use of liposomes in the diagnosis and management of ASCVD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Chronic hemodialysis is a lifesaving procedure for end-stage renal failure patients who may lead to the transmission of oncogenic viral infections discussed as a major cause of liver disease and a potential cause of substantial morbidity and mortality. In this regard, the hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common infections that studied recently. This study aimed to review systematically all available documents on the prevalence of hepatitis D virus (HED), hepatitis E virus (HEV), hepatitis G virus (HGV), human T-lymphotropic virus (HTLV), human immunodeficiency virus (HIV), and Kaposi's sarcoma-associated herpes virus (KSHV) in Iranian hemodialysis patients., Methods: We conducted a comprehensive systematic review of literature on the prevalence and factors associated with HED, HEV, HGV, HTLV, HIV, and KSHV in Iranian hemodialysis patients. Using Medical Subject Headings (MeSH) terms, Emtree, and related equal Persian key words, irrespective of age, date, and language, the main domestic databanks of Barekat, Scientific Information Database (SID), Iran-doc, and also international databases of PubMed and NLM Gateway (for MEDLINE), Institute of Scientific Information (ISI), and SCOPUS searched. Interest outcome of infection prevalence was confirmed based on reported positive tests of blood samples. Since the studied factors are very numerous and there is even a high heterogeneity in each factor, so the meta-analysis was not performed., Results: Based on our search strategy through comprehensive searching, 509 studies were found. From them, 314 articles were from international data bases and others from Iranian data banks. After excluding duplicates and overlapping studies, 41 studies were included in the analysis; 11 studies were relevant to HIV, 10 studies assigned to HEV, and 7 studies belonged to HGV field. The HDV, HTLV1,2, and KSHV were the other research subject areas. The prevalence of HIV, HGV, and HTLV1,2 ranged from 0% to 1.5%, 0% to 24.19%, and 0.6% to 70.4%, respectively, in different provinces., Conclusions: This is the comprehensive systematic review on oncogenic viral infections prevalence in the Iranian hemodialysis patients. Present findings emphasize on requirement to evidence-based practical intervention for better prevention and control of problem. The findings could be used as a scientific evidence for developing related policies and highlighting the future plan of complementary researches., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 International Journal of Preventive Medicine.)