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Background: Depression is a state of low mood and aversion to activity, which affects a person's thoughts, behavior, motivation, feelings, and sense of wellbeing. Pharmacologic therapies are still the best effective treatment of depression. Still, most antidepressant drugs have low efficacy and delayed onset of therapeutic action, have different side effects, and even exacerbate depression. Such conditions make it possible to look for alternatives. Consequently, we decided to summarize the impact of flavonoids on depression in this review., Methods: We searched scientific databases such as SCOPUS, PubMed, and Google Scholar to find relevant studies until July 2022., Results: A wide variety of natural components have been shown to alleviate depression, one of which is flavonoids. Due to the growing tendency to use natural antidepressant drugs, scientific studies are increasingly being conducted on flavonoids. This study aims to review the latest scientific researches that indicate the antidepressant potential of flavonoids. Various mechanisms include neurotransmitter system modulation and dopaminergic, noradrenergic, and serotonergic pathways regulation in the central nervous system. Different compounds of flavonoids have antidepressant properties in vivo or in vitro experiments or clinical trials and can be used as alternative and complementary treatments for depression. In general, it was observed that there were no severe side effects., Conclusion: Our study proves the antidepressant potential of flavonoids, and considering the limited side effects, they can be used as complementary medicine for depressed patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alizadeh, Pourfallah-Taft, Khoshnazar, Safdari, Komari, Zanganeh, Sami, Valizadeh, Faridzadeh, Alijanzadeh, Mazhari, Khademi, Kheirandish and Naziri.)

A few studies have examined post-traumatic growth (PTG) after burns, a relatively new area of research. To understand how to promote PTG in burn survivors, we need to know how PTG and coping are presented, how they change over time, and the components that influence development. Based on the criteria of the PRISMA statement, we conducted our initial search on 1 February 2023. This study systematically reviewed relevant studies in five PubMed, Web of Science, Google Scholar, Scopus and Science Direct search databases. The search used the following keywords: Post-traumatic Growth, Psychological Growth, Post-traumatic Growth, Psychological, PTG, Burns and Burn. The two researchers evaluated the quality of the included studies using a 20-item tool called the appraisal tool for cross-sectional studies (AXIS tool). A total of 1396 burn patients participated in 12 studies. Among the studies included in this systematic review, seven were cross-sectional, and five were cohort. The average age of the patients in this study was 35.77 (SD = 10.19). Among the participants, 52.4% were men. The total body surface area (TBSA) percentage in these patients was 32.77 (SD = 16.42). The mean of PTG inventory (PTGI) was 54.08 (SD = 20.46) out of 105, which is a moderate level. Factors such as coping strategies, perceived social support, TBSA, religion/spirituality and severity of burn are positive factors for PTG in burn survivors. Also, factors such as depression, post-traumatic stress disorder and physical and mental recovery are negative factors for PTG in burn survivors. These factors can be improved through targeted intervention strategies, including overall function, quality of life, social support, optimism, hope and new opportunities. There is a need for further research in several areas related to growth, intervention and measurement., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background and Purpose: A Farsi version of the Heartland Forgiveness Scale (HFS-F) for assessing forgiveness in Iranian cardiovascular patients was not available. This study aimed to determine the validity and reliability of the Farsi version of HFS in this population. Methods: In this methodological cross-sectional research design, 400 Iranian cardiovascular patients completed the HFS-F between October 2019 and January 2020. We assessed the characteristics, content, and both exploratory and confirmatory construct validity of the measures. To evaluate the reliability and construct validity of the HFS-F, we calculated Cronbach's alpha, McDonald's omega, and the Intraclass Correlation Coefficient. Results: Three factors were identified following confirmatory and deterministic factor analyses. The extracted factors demonstrated satisfactory reliability, exceeding a threshold of 0.7. Conclusions: The HFS-F exhibited a robust level of validity and reliability, rendering it a suitable instrument for future research endeavors., (© 2024 Springer Publishing Company.)

Background: Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by dopamine depletion and severe motor impairments. Preladenant, an adenosine A2 receptor antagonist, is an investigational treatment for PD. This systematic review and meta-analysis aimed to critically evaluate the efficacy of Preladenant in improving motor symptoms in patients with PD., Methods: A comprehensive literature search was conducted in PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to March 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials (RCTs) comparing Preladenant with placebo in PD patients were included. The primary outcome was the change in daily ON time without troublesome dyskinesia. Secondary outcomes included the change in daily OFF time and adverse events. The risk of bias was assessed using the Cochrane Risk of Bias tool., Results: Four RCTs with a total of 2097 PD patients were included. Pooled analysis showed that Preladenant could generally increase daily ON time (pooled effect 0.15 and 95 % CI: -0.19-0.48) and reduce daily OFF time (pooled effect -0.04 and 95 % CI: -0.43-0.36) compared to placebo, however it was not significant. The included studies had moderate to high heterogeneity. No significant differences in adverse events were observed between Preladenant and placebo., Conclusion: This meta-analysis suggests that Preladenant may improve motor fluctuations in PD patients by increasing ON time and reducing OFF time. However, the high heterogeneity among studies warrants further large-scale, high-quality RCTs to confirm these findings and establish the long-term safety and efficacy of Preladenant in PD management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Inc. on behalf of International Brain Research Organization.)

Introduction: The present study employs bioinformatics tools to identify shared upregulated genes between chemical burns and gastric cancer., Methods: Gene Expression Omnibus (GEO) retrieved gene sets for this investigation. GSEs with P value less than 0.05 and LOG fold change (FC) greater than 1 were valid and upregulated. Gastric cancer and chemical burn common elevated genes were found using Venn diagram online tools. In the second stage, the "string" visualized gastric cancer elevated genes network, and non-coding RNAs were deleted, and "interaction" greater than 1 was examined to choose important gene nodes. Next, they explored the String gene-interaction network for common genes. To determine the most interacting genes, Gephi (V 0.9.7) used "betweenness centrality" greater than "0" to evaluate the twenty-gene network. TISIDB and drug banks provide gene-related medications., Results: In the present study, two genes, including ALOX5AP and SERPINB2, were obtained, with the highest centrality among chemical burns and gastric cancer shared genes. Additionally, the current study presented five drugs, including Urokinase, Tenecteplase, DG031, AM103, and Fiboflapon, which can have predicted effects on gastric cancer following chemical burns., Conclusion: According to current in-silicon analyses, ALOX5AP and SERPINB2 are linked genetic keys between gastric chemical burn and cancer. Considering that burn is an environmental factor that leads to the upregulation of the two genes thus, the chemical burn can be related to the incidence of gastric cancer., Competing Interests: The authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: The present study aimed to examine the psychometric properties of the Persian version of the Mendelson and White Body Esteem Scale in Iranian adults. Methods: This cross-sectional study design was used and carried out in 2023. Following the inclusion criteria, 500 adults were gathered from Tehran (Tehran, Iran) with an accessible sampling method. After translation of Body Esteem Scale to Persian language, construct validity (with factor analysis and exploratory graph analysis) and reliability were assessed. Results: The mean age of the participants was 30.66 (standard deviation = 7.40) years. The results of Maximum Likelihood Exploratory Factor Analysis (MLEFA) with Promax with Kaiser normalization rotation extracted three factors accounting for 43.4% of the variance comprising 21 items. Also, after necessary modifications during confirmatory factor analysis, the final model was approved. As for construct reliability, the Cronbach's alpha, Composite Reliability, and Maximal Reliability for all constructs were greater than 0.7, demonstrating good internal consistency and construct reliability. Conclusions: According to results, the Persian version of Body Esteem Scale has a valid structure and acceptable reliability. This scale can be used by health professionals in many ways., (© 2024 Springer Publishing Company.)

Due to the growth of the elderly population, age-related neurological disorders are an increasing problem. Aging begins very gradually and later leads to several neurological issues such as lower neurotransmitter levels, oxidative stress, neuronal inflammation, and continual neuronal loss. These changes might contribute to brain disorders such as Alzheimer's disease (AD), dementia or mild cognitive impairment, and epilepsy and glioma, and can also aggravate these disorders if they were previously present. Momordica charantia (bitter gourd), a member of the Cucurbitaceae family, is a good source of carbohydrates, proteins, vitamins, and minerals. It is used for diabetes and known for its hypoglycemic and antioxidant effects. In this review, we discuss the pharmaceutical effects of M. charantia on age-related neurological disorders. We searched several databases, including PubMed and Google Scholar, using MeSH terms. We searched articles published up until 2022 regardless of publication language. M. charantia is rich in luteolin, which increases acetylcholine in neurons by binding to enzymes in acetylcholine metabolism pathways, including butyrylcholinesterase and acetylcholinesterase. This binding inhibits the hyperphosphorylation of tau protein by restraining its kinase enzyme. Furthermore, this substance can lower serum cholesterol and has multi-target activity in AD and memory loss. M. charantia can also improve memory by decreasing tau protein and it also has potent antioxidant activity and anti-inflammatory effects. This review highlights that M. charantia has effects on many age-related neurological disorders, and can be a cost-effective supplement with minimal side effects., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Introduction: Burn injuries lead to dysregulation of immune molecules, impacting cellular and humoral immune pathways. This study aims to determine the prediction of immune molecule activity during burn wound healing among elderly patients., Methods: The current study utilized the Gene Expression Omnibus (GEO) database to extract the proper gene set. Also, the literature review was conducted in the present study to find immune signatures. The study used the "enrich r" website to identify the biological functions of extracted genes. The critical gene modules related to mortality were identified using the weighted gene co-expression network analysis (WGCNA) R package., Results: The appreciated GSE was extracted. According to the data, the most upregulated signatures were related to natural killer (NK) cells, and the most downregulated signatures were associated with M1 macrophages. Also, the results of WGCNA have shown that the most related gene modules ( P <107 and score 0.17) to mortality were investigated, and the modules 100 first genes were extracted. Additionally, the enrich r analysis has demonstrated related pathways, including the immune process, including regulation of histamine secreted from mast cell ( P <0.05), T helper 17 cell differentiation ( P <0.05), and autophagy ( P <0.05) were obtained. Finally, by network analysis, the critical gene "B3GNT5" were obtained (degree>ten and "betweenness and centrality">30 were considered)., Conclusion: The study identified significant changes in macrophage and NK cell expression patterns post-burn injury, linking them to potential improvements in clinical outcomes and wound healing. The gene B3GNT5, associated with mortality, was highlighted as a key marker for prognostic evaluation., Competing Interests: The authors have no conflicts of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Clear cell renal cell carcinoma (ccRCC) is a form of kidney cancer characterized by dysregulated angiogenesis and multidrug resistance. Hypoxia-induced tumor progression plays a crucial role in ccRCC pathogenesis. Beta-hydroxybutyrate (BHB) and quercetin (QCT) have shown potential in targeting angiogenesis and drug resistance in various cancer types. This study investigates the combined effects of BHB and QCT in hypoxia-induced Caki-1 cells., Methods: Caki-1 cells were subjected to normoxic and hypoxic conditions and treated with BHB, QCT, or a combination of both. Cell-viability was assessed using the MTT assay, and mRNA expression levels of key angiogenesis-related genes (HIF-1α/2α, VEGF, Ang-1, Ang-2, and MDR4) were quantified through real-time PCR during 24 and 48 h., Results: BHB and QCT treatments, either alone or in combination, significantly reduced cell-viability in Caki-1 cells (p < 0.05). Moreover, the combined therapy demonstrated a potential effect in downregulating the expression of angiogenesis-related genes and MDR4 in hypoxia-induced cells, with a marked reduction in HIF-1α/2α, VEGF, Ang-1, and MDR4 expression (p < 0.05). The expression of Ang-2 increases significantly in presence of BHB combined QCT treatment., Conclusion: This study highlights the promising potential of a combination therapy involving BHB and QCT in mitigating angiogenesis and MDR4 expression in hypoxia-induced ccRCC cells. These findings support further investigation into the underlying mechanisms and warrant clinical studies to evaluate the therapeutic value of this combined treatment for ccRCC patients. This research provides new insights into addressing the challenges posed by angiogenesis and drug resistance in ccRCC., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Evaluating complications and mortality risks in burn patients is crucial for effective treatment planning and improving survival rates. This study investigated the relationship between the serum vitamin D level and the clinical outcomes of adult burns patients. This was a prospective cohort of adult patients hospitalized due to thermal burns at a burn centre in the north of Iran. Based on the level of 25 hydroxyvitamin D measured upon admission, patients were divided into two groups of patients with sufficient 25 hydroxyvitamin D level and insufficient 25 hydroxyvitamin D level. Descriptive statistics were used for baseline demographics. Univariate analysis was conducted using Mann-Whitney U, Chi-square, independent samples, and Fisher's exact tests. A multivariate logistic regression was performed to adjust for the effects of confounding variables. Statistical analyses were conducted using SPSS 28.0 software. A total of 220 patients were included in the study. The average total body surface area burned was 30.52 ± 9.34. Patients with insufficient vitamin D levels had longer hospital stays (12.53 vs. 11.45) and longer stays in the intensive care unit (ICU) (3.32 vs. 2.40) than those with appropriate vitamin D levels. Participants with insufficient vitamin D levels exhibited a numerically higher incidence of infections than those with adequate levels (p < 0.05). The multivariate regression found that vitamin D deficiency levels were associated with increased infection rates and prolonged hospital stay. This study suggests that vitamin D deficiency is a significant risk factor for adverse clinical outcomes in burn patients. Further research is needed to confirm these associations and to explore potential interventions to optimize vitamin D status in this patient population., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions., Methods and Results: The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls. The mRNA expression levels of neurotrophin growth factors and their receptors were measured using quantitative PCR. A Bayesian regression model was used in the research to assess the relationship between gene expression levels and demographic characteristics such as age and gender. The correlations between variables were analyzed using Spearman correlation coefficients, and the diagnostic potential was assessed using a Receiver Operating Characteristic curve. NTRK2, TrkA, TrkC, and BDNF expression levels were found to be considerably lower (p-value < 0.05) in the blood samples of AD patients compared to the control group. The expression of BDNF exhibited the most substantial decrease in comparison to other neurotrophin growth factors. Correlation analysis indicates a statistically significant positive association between the genes. The ROC analysis showed that BDNF exhibited the greatest Area Under the Curve (AUC) value of 0.76, accompanied by a sensitivity of 70% and specificity of 66%. TrkC, TrkA, and NTRK2 demonstrated considerable diagnostic potential in distinguishing between cases and controls., Conclusion: The observed decrease in the expression levels of NTRK2, TrkA, TrkC, and BDNF in AD patients, along with the identified associations between specific genes and their diagnostic capacity, indicate that these expressions have the potential to function as biomarkers for the diagnosis and treatment of AD., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Aims: The current systematic review aimed to elucidate the effects of lipid variability on microvascular complication risk in diabetic patients. The lipid components studied were as follows: High-density lipoprotein (HDL), High-density lipoprotein (LDL), Triglyceride (TG), Total Cholesterol (TC), and Remnant Cholesterol (RC)., Method: We carried out a systematic search in multiple databases, including PubMed, Web of Science, and SCOPUS, up to October 2nd, 2023. After omitting the duplicates, we screened the title and abstract of the studies. Next, we retrieved and reviewed the full text of the remaining articles and included the ones that met our inclusion criteria in the study., Result: In this research, we examined seven studies, comprising six cohort studies and one cross-sectional study. This research was conducted in Hong Kong, China, Japan, Taiwan, Finland, and Italy. The publication years of these articles ranged from 2012 to 2022, and the duration of each study ranged from 5 to 14.3 years. The study group consisted of patients with type 2 diabetes aged between 45 and 84 years, with a diabetes history of 7 to 12 years. These studies have demonstrated that higher levels of LDL, HDL, and TG variability can have adverse effects on microvascular complications, especially nephropathy and neuropathic complications. TG and LDL variability were associated with the development of albuminuria and GFR decline. Additionally, reducing HDL levels showed a protective effect against microalbuminuria. However, other studies did not reveal an apparent relationship between lipid variations and microvascular complications, such as retinopathy. Current research lacks geographic and demographic diversity. Increased HDL, TG, and RC variability have been associated with several microvascular difficulties. Still, the pathogenic mechanism is not entirely known, and understanding how lipid variability affects microvascular disorders may lead to novel treatments. Furthermore, the current body of this research is restricted in its coverage. This field's lack of thorough investigations required a more extensive study and comprehensive effort., Conclusion: The relationship between lipid variation (LDL, HDL, and TG) (adverse effects) on microvascular complications, especially nephropathy and neuropathic (and maybe not retinopathy), is proven. Physicians and health policymakers should be highly vigilant to lipid variation in a general population., (© 2023. The Author(s).)

Background: Early colorectal cancer (CRC) diagnosis can drastically reduce CRC-related morbidity and mortality. In this regard, increasing attention is now being directed to DNA-based tests, especially the evaluation of methylation levels, to prioritize high-risk suspected persons for colonoscopy examination. Therefore, we aimed to assess the accuracy of MGMT gene promoter methylation levels in peripheral blood mononuclear cells (PBMCs) for distinguishing CRC patients from healthy people., Materials and Methods: For this study, a total of seventy individuals with CRC and 75 healthy individuals from Iran were included. The methylation level of MGMT in the DNA isolated from PBMCs was evaluated using the methylation quantification endonuclease-resistant DNA technique. To assess the diagnostic capability of the MGMT promoter methylation level, a receiver operating characteristic (ROC) curve was generated., Results: The mean promoter methylation level of MGMT in the CRC and control groups was, respectively, 27.83 ± 22.80 vs. 12.36 ± 14.48. The average percentage of methylation of the MGMT promoter between the CRC and control groups was significantly different ( P < 0.001). Also, the MGMT promoter was more hypermethylated in female patients than in males. ROC analyses indicated that the diagnostic power of the MGMT promoter methylation level for CRC was 0.754, with a sensitivity of 81.43% and a specificity of 75.71%, indicating a good biomarker for CRC diagnosis., Conclusion: Methylation evaluation of MGMT in PBMCs could be utilized as a diagnostic biomarker with high accuracy for prioritizing suspected CRC patients before colonoscopy., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)

Introduction: Considering the importance of delirium disorder in burn patients and its complications, the present systematic review and meta-analysis aimed to determine the prevalence of delirium and its related factors in burn patients., Methods: A comprehensive, systematic search was performed in different international electronic databases, such as Scopus, PubMed, and Web of Science, as well as Persian electronic databases such as Iranmedex, and Scientific Information Database (SID) using keywords extracted from Medical Subject Headings such as "Prevalence", "Delirium", and "Burns" from the earliest to the 17th of July, 2023., Results: In total, 2,710 burn patients participated in ten original studies. Among the participants, 64.6% were male. In the ten studies, the reported pooled prevalence of delirium among burn patients was 20.5% (95% CI: 10.9% to 35.0%; I 2 =96.889%; P<0.001). Also, factors such as total body surface area, duration of hospitalization, mortality, days on ventilator, alcoholism, benzodiazepine dose, methadone dose, age, male gender, ICU days, operation days, wound care under anesthesia, and opioid dose had a significant correlation with the prevalence of delirium in burn patients., Conclusion: Health managers and policymakers can reduce the prevalence of delirium in burn patients by eliminating or reducing factors associated with it., Competing Interests: The authors declare no conflict of interest.

Introduction: Pain experienced during the insertion of a catheter into the arteriovenous fistula (AVF) and restless legs syndrome (RLS) are prevalent issues among Hemodialysis (HD) patients. The primary objective of this systematic review and meta-analysis was to consolidate the findings from randomized clinical trial (RCT) studies examining the impact of aromatherapy with lavender on the pain associated with AVF catheter insertion and RLS in HD patients., Methods: A systematic search was conducted on PubMed, Web of Science, Scopus, Cochrane, Embase, ClinicalTrials.gov, and Google Scholar search engine from inception to August 1, 2022, using keywords extracted from Medical Subject Headings, such as "Aromatherapy", "Lavender", "Arteriovenous fistula", "Pain", "Restless legs syndrome", and "Hemodialysis"., Results: Finally, eleven articles were included in this systematic review and meta-analysis. The results showed that aromatherapy reduced the average pain of catheter insertion in AVF compared to the control group (Standard Mean Difference: -1.60, 95% Confidence Interval: -2.32 to -0.87, Z=4.32, I 2 :90.3%, P<0.001). Also, aromatherapy massage reduced the average severity of RLS compared to the control group, which was statistically significant (Weighted Mean Difference: -13.21, 95% Confidence Interval: -17.50 to -8.91, Z=6.03, I 2 :93.0%, P<0.001). Also, the subgroup analysis showed that lavender in the intervention group significantly decreased the pain intensity compared to the "no intervention" group (P<0.001), yet it was not significant compared to the placebo group (P=0.12)., Conclusion: In summary, the findings indicate a notable reduction in catheter insertion pain in AVF and relief from RLS among HD patients through the use of lavender essential oil. As a result, future research is encouraged to include a comparison of lavender's effects with those of a placebo group., Competing Interests: The authors declare that there is no conflict of interest.

Introduction: In the absence of timely treatment, the risk of rupture in patients with ectopic pregnancy (EP) increases, which is associated with extensive bleeding, complicated surgery, and maternal death. This study aimed to investigate the prevalence of rupture and its related factors among EP cases., Methods: A comprehensive, systematic search was conducted in electronic databases, such as Scopus, PubMed, Web of Science, and Persian electronic databases such as Iranmedex, and Scientific Information Database using keywords extracted from Medical Subject Headings such as "Ectopic pregnancies", "Extrauterine pregnancies", and "Ruptured ectopic pregnancy" from the earliest to the 13th of December 2022. The CMA program, version 3, was utilized for analysis. The overall effect size was calculated using the sample size and the frequency of rupture in each of the studies. Heterogeneity was measured using the I 2 statistics., Results: A total of 5,269 women with EP participated in 17 studies. The pooled prevalence of rupture was 56.4% (95%CI: 44.9% to 67.2%; I 2 =98.09%; P<0.001). Factors such as number of parties, amount of β-hCG, age, history of ectopic pregnancy, cornual and isthmic pregnancies, gestational age, number of gravidities, history of tubal ligation, tubal diameters, periods of infertility, history of infertility, pregnancy by ovulation induction, extensive hemoperitoneum, ampullar and isthmic pregnancies, ampullar pregnancies, preoperative heart rate (HR), triage, triage shock index (SI), abdominal pain, single marital status, preoperative hemoglobin levels, preoperative hematocrit levels, history of pelvic inflammatory disease (PID), and use of contraceptives were associated with the prevalence of rupture in EP cases., Conclusion: Based on the findings, 56.4% of EP cases experienced rupture and various factors influence its prevalence. As a result, health managers and policymakers can address and mitigate modifiable factors contributing to rupture in EP cases by implementing regular consultations and screenings., Competing Interests: The authors declare no conflict of interest.

Background: Traditionally, the diagnosis and monitoring of disease activity in systemic lupus erythematosus (SLE) are contingent upon clinical manifestations and serological markers. However, researchers are struggling to find biomarkers with higher sensitivity and specificity. DNA methylation has been the most studied epigenetic feature in SLE. So, in this study, we performed a systematic review of studies about DNA methylation alterations in SLE patients compared to healthy controls., Methods: By searching PubMed, Scopus, and Google Scholar up to July 2022, all case-control studies in which DNA methylation of specific genes was assessed by a non-high-throughput technique and passed the quality of bias assessment were included., Results: In total, 44 eligible studies underwent a data extraction process. In all, 3471 SLE patients and 1028 healthy individuals were included. Among the studies that reported the patients' gender ( n = 2853), 89.41% were female and 10.59% were male. Forty studies have been conducted on adult patients. The number of works on fractionated and unfractionated blood cells was almost equal. In this regard, 22 studies were conducted on whole blood or peripheral blood mononuclear cells and two studies on unfractionated white blood cells. Sorted blood cells were biological sources in 20 studies. The most investigated gene was IFI44L . Sensitivity, specificity, and diagnostic power of methylation levels were only reported for IFI44L in five studies. The most employed methylation profiling method was bisulfite sequencing polymerase chain reaction. The correlation between methylation patterns and clinical parameters was explored in 22 studies, which of them 16 publications displayed a remarkable association between DNA methylation status and clinical indices., Conclusions: The methylation status of some genes especially IFI44L , FOXP3 , and MX1 has been suggested as promising SLE biomarkers. However, given the conflicting findings between studies because of potential confounders such as different sample types, methylation profiling methods, and ethnicity as well as shared DNA methylation patterns of SLE and other autoimmune diseases, DNA methylation biomarkers are currently not reliable diagnostic biomarkers and do not represent surrogate markers of SLE disease activity. Future investigations on a larger scale with the discarding of limitations of previous studies would probably lead to a consensus.