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Background: Alopecia areata (AA) commonly displays as non-scarring, irregular hair loss. Experimental and clinical research have specifically implicated autoimmunity and genetics in the disruption of anagen hair follicles. AA patients' scalp lesions and peripheral blood mononuclear cells (PBMCs) exhibited an immune state imbalance. Numerous studies attempt to establish a connection between the occurrence and prognosis of AA and the epigenetic modulation of gene expression by long noncoding RNA (lncRNA) and microRNA (miRNA). The current study aimed to examine the serum levels of nuclear enriched abundant transcript 1 (NEAT1) and its target miRNA101 (miR-101) in AA and investigate the ability to use them as diagnostic biomarkers in the disease. Methods: Seventy-two AA patients were included in this prospective cohort study. Demographics, patient history, laboratory characteristics, and treatments were recorded. The miR-101 and NEAT1 levels were evaluated. Results: Serum NEAT1 levels were lower in AA patients, but there was no significant difference. However, there was no substantial disparity in NEAT1 level regarding other disease characteristics. There was a substantial positive association between NEAT1 and miR-101 levels among cases. On the other hand, the results showed a markedly low mean of miR-101 levels among patients, but the miR-101 marker shows no significant difference regarding different disease characteristics. The specificity and sensitivity test for the miR-101 marker shows a significant specificity of 60 % and sensitivity of 75 % with a p-value of 0.001 and a cut-off value of 0.897. Conclusions: The current research determined that miR-101 works as a diagnostic biomarker for AA.

Background Trichodynia or hair pain refers to the painful sensation occurring in the hair and or scalp in the setting of hair shedding. It has been reported mainly in association with telogen effluvium and androgenetic alopecia (AGA). Recently, trichodynia cases have been growing in numbers. Several theories have been proposed to explain the pathogenesis of trichodynia, suggesting a major role for substance P (SP) accompanied by perifollicular inflammation. Objective To assess tissue and serum levels of SP in trichodynia occurring in AGA patients. Patients and methods This is a case–control study that included 35 patients of trichodynia in AGA as well as 35 age-matched and sex-matched healthy participants included as controls. The diagnosis was made by clinical, trichoscopic examination, and scalp biopsy. Tissue and serum levels of SP were measured using the enzyme-linked immunoassay technique. Results The mean tissue levels of SP were significantly higher in patients (448.11±241.24 pg/g), than in controls (75.78±11.81 pg/g) (P

Abstract Vitiligo is a common long-term depigmenting skin disorder that is characterized by patches of skin losing their pigment. To evaluate serum/tissue levels of miR-16, 146a, 19b and 720 in vitiligo patients and healthy controls, also analyzing the correlations between all biomarkers to indicate whether those can be used to early diagnose vitiligo patients. Forty-subjects were included, divided into two equal groups, 20 healthy matched individuals and 20 vitiligo patients. For all groups a 5 mL venous blood sample for serum isolation was taken and analyzed for the serum level of miRNAs. For tissue analysis, 3 mm biopsy was taken. For all patients Vitiligo area scoring index (VASI), vitiligo disease activity (VIDA), disease duration and extent percentages were calculated. No significant difference was observed in age and sex ratio among the two groups (p > 0.05). Serum, expression levels for miR-16, 146a, and 19b were overexpressed in vitiligo patients as compared to healthy controls with p-value 0.000 for all biomarkers. While miR-720 was reported low in vitiligo patients compared to controls (p = 0.000). For tissue samples, miR-16, 146a, 19b were overexpressed in vitiligo patients with p-values 0.000, 0.000 and

Abstract Background Oral Lichen Planus is one of the most popular chronic mucocutaneous diseases. It is classified as potentially malignant lesions. Many microRNAs can be used as biological markers for the disease and for its malignant transformation. The aim of the study to measure the expression of microRNA-93 and microRNA-412-3p in Oral Lichen Planus patients, patients diagnosed as Oral Squamous Cell Carcinoma and healthy controls. Methodology A total of 60 patients were divided into 3 groups; each group contains 20 patients. Group I for Oral Lichen Planus patients, group II for healthy controls and group III for Oral Squamous cell carcinoma patients. All of these patients were chosen from those attending Kasr Al-Einy hospital, Cairo University. After full diagnosis and matching of our eligibility criteria, saliva sample was taken from each patient to measure the concentration of microRNA-93 and microRNA-412-3p. Results Both microRNA-93 and miceoRNA-412-3p were upregulated in Oral Squamous cell carcinoma patients than Oral Lichen patients than controls and both of them had great sensitivity, specificity and diagnostic accuracy for both Oral Lichen Planus and Oral Squamous cell carcinoma. Conclusion MicroRNA-93 and micriRNA-412-3p can be used as diagnostic markers and for the oncogenic potential of Oral Lichen Planus.

To date, the epigenetic signature of preeclampsia (PE) is not completely deciphered. Oxidative stress-responsive long non-coding RNAs (lncRNAs) are deregulated in preeclamptic placenta; however, their circulating profiles and diagnostic abilities are still unexplored. We investigated serum redox-sensitive lncRNAs TUG1, H19, and NEAT1, and their target miR-29b/cystine/neutral/dibasic amino acids transporter solute carrier family 3, member 1 (SLC3A1) as potential non-invasive biomarkers of PE risk, onset, and severity. We recruited 82 patients with PE and 78 healthy pregnant women. We classified PE patients into early-onset (EOPE) and late-onset (LOPE) subgroups at a cut-off 34 gestational weeks and into severe and mild PE subgroups by blood pressure and proteinuria criteria. Bioinformatics analysis was employed to select lncRNAs/microRNA/target gene interactions. Serum H19, NEAT1, and SLC3A1 mRNA expression were reduced, meanwhile miR-29b levels were elevated, whereas there was no significant difference in TUG1 levels between PE patients and healthy pregnancies. Serum H19 levels were lower, whereas miR-29b levels were higher in EOPE versus LOPE. Serum miR-29b and H19 levels were higher in severe versus mild PE. ROC analysis identified serum H19, NEAT1, miR-29b, and SLC3A1 as potential diagnostic markers, with H19 (AUC = 0.818, 95%CI = 0.744–0.894) and miR-29b (AUC = 0.82, 95%CI = 0.755–0.885) were superior discriminators. Only H19 and miR-29b discriminated EOPE and severe PE cases. In multivariate logistic analysis, miR-29b and H19 were associated with EOPE, using maternal age and gestational age as covariates, while miR-29b was associated with severe PE, using maternal age as covariate. Studied markers were correlated with clinical and ultrasound data in the overall PE group. Serum H19 and TUG1 were negatively correlated with albuminuria in EOPE and LOPE, respectively. NEAT1 and SLC3A1 were correlated with ultrasound data in EOPE. Likewise, TUG1, miR-29b, and SLC3A1 showed significant correlations with ultrasound data in LOPE. Conclusively, this study configures SLC3A1 expression as a novel potential serum biomarker of PE and advocates serum H19 and miR-29b as biomarkers of EOPE and miR-29b as a biomarker of PE severity.

Abstract Background and objectives Behçet’s disease (BD) is an ongoing systemic vasculitis with mouth and genital ulceration and eye, skin, and systemic affection. It has considerable morbidity and mortality, and a high incidence and a higher male-to-female affection characterize Egypt. We aimed to evaluate liver x receptor messenger RNA beta (LXR β) and microRNA-146a (miR-146a) gene expression in Behçet’s disease cases in Egypt to relate them with clinicopathological features. Subject and method Eighty Egyptian individuals were split into two groups for the current study: Forty Behçet’s disease cases and forty healthy controls matched by age and gender from the Rheumatology Department at Helwan University Hospital, Egypt. The transformed score, also known as the Behçet’s Disease Current Activity Form (BDCAF), was utilized to measure disease activity. To assess the amounts of LXR β and miR-146a serum expression via real-time PCR, a blood sample was obtained. Results There was a downregulation of both LXR β and miR-146a levels that significantly differed between the BD group and the control group (p = 0.0001 and 0.0001, respectively). There is a noteworthy inverse relationship between the expression level of LXR β and BDCAF Patients Index (r = − 0.79 and p = 0.0001) was found. Regarding miR-146a, it had a reverse correlation with BDCAF Patients Index (r = − 0.89 and p = 0.0001). Conclusion LXR β and miR-146a were found to be significant non-invasive predictor biomarkers for Behçet’s disease and can indicate disease activity.

Abstract Background Noncoding RNAs play pivotal roles in the process of autoimmune diseases. However, the definite contributions of these molecules to Behçet’s disease (BD) are still unknown. This study aimed to explore the clinical value of a novel competing endogenous (ce) RNA network in the pathogenesis of BD and to assess its use in primary diagnosis. Methods Bioinformatic analysis was applied to construct a BD-related ceRNA network: lncRNA (MIAT and PVT1)-miRNA (miR-93-5p and miR-124-3p)-mRNA (SOD-2 and MICA). Blood was obtained from 70 BD patients and 30 healthy subjects, and the serum expression of the tested RNAs was estimated via quantitative real-time PCR (qPCR). Serum tumor necrosis factor-alpha (TNF-α) levels were also determined. The associations between these RNAs were further analyzed, and receiver operating characteristic (ROC) curve and logistic regression analyses were employed to validate their diagnostic and prognostic values. Results The expression levels of the lncRNAs PVT1 and miR-93-5p were significantly increased, whereas those of the lncRNAs MIAT and miR-124-3p, as well as those of the SOD-2 and MICA mRNAs, were significantly decreased in BD patients compared with controls. BD patients had significantly higher serum TNF-α levels than controls did. ROC curve analysis indicated that the selected RNAs could be candidate diagnostic biomarkers for BD. Moreover, the highest diagnostic efficiency was achieved with the combination of MIAT and miR-93-5p or PVT1 and miR-124-3p with either SOD-2 or MICA. Logistic regression analysis revealed that all RNA expression levels could be predictors for BD. Conclusion Mechanistically, our research revealed a novel ceRNA network that is significantly disrupted in BD. The findings reported herein, highlight the noncoding RNA-molecular pathways underlying BD and identify potential targets for therapeutic intervention. These insights will likely be applicable for developing new strategies for the early diagnosis, management and risk assessment of BD as well as the design of novel preventive measures. Trial registration The protocol for the clinical studies was approved by Cairo University’s Faculty of Pharmacy’s Research Ethics Committee (approval number: BC 3590)

Abstract Background Nitric oxide (NO) may contribute to the persistence of high-risk human papillomavirus (hrHPV) infection, which has been linked to the development of premalignant lesions and cervical cancer. Our study aimed to examine the relationship between cervical NO metabolite (NOx) levels, hrHPV infection, and cytopathological findings. Additionally, we assessed cervical NOx levels as a biomarker for predicting hrHPV infection and epithelial atypia. Methods The study involved 74 women who attended the Gynecology and Obstetrics outpatient clinics at Cairo University Hospitals between November 2021 and August 2022. Cervical samples were subjected to Pap testing, assessment of NOx levels by the Griess method, and detection of hrHPV DNA by real-time polymerase chain reaction. Results High-risk HPV was detected in 37.8% of women. EA was found in 17.1% of cases, with a higher percentage among hrHPV-positive than negative cases (35.7% vs. 4.3%, p = 0.001). The most prevalent hrHPV genotype was HPV 16 (89.3%). The cervical NOx level in hrHPV-positive cases was significantly higher (37.4 µmol/mL, IQR: 34.5–45.8) compared to negative cases (2.3 µmol/mL, IQR: 1.2–9.8) (p = 23.61 µmol/mL and > 11.35 µmol/mL exhibited good diagnostic accuracy for the prediction of hrHPV infection and EA, respectively. Conclusions The high prevalence of hrHPV infection, particularly HPV 16, in our hospital warrants targeted treatment and comprehensive screening. Elevated cervical NOx levels are associated with hrHPV infection and high-grade atypia, suggesting their potential use as biomarkers for predicting the presence of hrHPV and abnormal cytological changes.

Abstract Background Diabetes mellitus is a disease that may result from interaction between environmental factors and a strong genetic component. The current study is aimed at exploring three single nucleotide polymorphisms to identify the associated ones with type 2 diabetes in the Egyptian society. The studied single nucleotide polymorphisms (rs10096097 in GOAT, rs6740584 in CREB1, and rs62521874 in MAFA) were examined via genotyping cases (n = 98) and irrelevant healthy subjects (n = 82). Results Associations were checked using dominant, recessive, genotypic, allelic, and Cochran–Armitage trend models. By comparing diabetic patients with controls, rs6740584 was associated with type 2 diabetes by employing all used models except the recessive model. Rs10096097 was connected with type 2 diabetes using the genotypic association, Cochran–Armitage trend test, and recessive model and not any other model. Rs62521874 was not linked with type 2 diabetes in all models. Moreover, haplotype association for rs10096097 and rs62521874 was conducted as these two single nucleotide polymorphisms were located on the same chromosome. The haplotype pattern rs10096097:G—rs62521874:A was identified as a biomarker for type 2 diabetes susceptibility in the Egyptian community. Conclusions The GOAT and CREB1 polymorphisms showed susceptibility to type 2 diabetes. Moreover, MAFA had no role in the disease except through the haplotype with GOAT polymorphism.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16–9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57–16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p

Abstract The identification of novel screening tools is imperative to empower the early detection of colorectal cancer (CRC). The influence of the long non-coding RNA maternally expressed gene 3 (MEG3) rs941576 single nucleotide polymorphism on CRC susceptibility remains uninvestigated. This research appraised MEG3 rs941576 association with the risk and clinical features of CRC and obesity-related CRC and its impact on serum MEG3 expression and its targets miR-27a/insulin-like growth factor 1 (IGF1)/IGF binding protein 3 (IGFBP3) and miR-181a/sirtuin 1 (SIRT1), along with the potential of these markers in obesity-related CRC diagnosis. 130 CRC patients (60 non-obese and 70 obese) and 120 cancer-free controls (64 non-obese and 56 obese) were enrolled. MEG3 targets were selected using bioinformatics analysis. MEG3 rs941576 was associated with magnified CRC risk in overall (OR (95% CI) 4.69(1.51–14.57), P = 0.0018) and stratified age and gender groups, but not with obesity-related CRC risk or MEG3/downstream targets’ expression. Escalated miR-27a and IGFBP3 and reduced IGF1 serum levels were concomitant with MEG3 downregulation in overall CRC patients versus controls and obese versus non-obese CRC patients. Serum miR-181a and SIRT1 were upregulated in CRC patients versus controls but weren’t altered in the obese versus non-obese comparison. Serum miR-181a and miR-27a were superior in overall and obesity-related CRC diagnosis, respectively; meanwhile, IGF1 was superior in distinguishing obese from non-obese CRC patients. Only serum miR-27a was associated with obesity-related CRC risk in multivariate logistic analysis. Among overall CRC patients, MEG3 rs941576 was associated with lymph node (LN) metastasis and tumor stage, serum MEG3 was negatively correlated with tumor stage, while SIRT1 was correlated with the anatomical site. Significant correlations were recorded between MEG3 and anatomical site, SIRT1 and tumor stage, and miR-27a/IGFBP3 and LN metastasis among obese CRC patients, while IGF1 was correlated with tumor stage and LN metastasis among non-obese CRC patients. Conclusively, this study advocates MEG3 rs941576 as a novel genetic marker of CRC susceptibility and prognosis. Our findings accentuate circulating MEG3/miR-27a/IGF1/IGFBP3, especially miR-27a as valuable markers for the early detection of obesity-related CRC. This axis along with SIRT1 could benefit obesity-related CRC prognosis.

Background and aims: Systemic sclerosis (SSc) is a common autoimmune disorder involving the skin, blood vessels, and internal organs with an elusive pathophysiology. SSc is believed to be a genetically prone T-cell-mediated autoimmune disease. miRNAs and lncRNAs were thought to be involved in the etiology of several immunological diseases including SSc. This work aimed to assess the expression of miRNA-133, lncRNA-H19, PKM2, and TGF-β levels in SSc in comparison to controls and their relationship to the clinical course and severity of disease. Patients and methods: Fifty patients with SSc and 40 healthy age and sex-matched controls were included in this study. miRNA-133 and H19 expression levels were detected using quantitative RT-PCR while serum levels of PKM2 and TGF-β were measured using ELISA techniques. Patients’ clinical data and treatments received were extracted and correlated with proteins investigated. Results: Our results showed that miRNA-133 was significantly downregulated in SSc patients in comparison to controls (Mean + SD of SSc = 0.61 ± 0.22, Mean ± SD of HC = 0.97 ± 0.007, p = 0.003). However, there was significant upregulation of the serum expressions of all other tested biomarkers in SSc patients in comparison to controls; H19 (Mean + SD of SSc = 10.37 ± 3.13, Mean ± SD of HC = 1.01 ± 0.01, p = 0.0001), PKM2 (Mean + SD of SSc = 28.0 ± 4.84, Mean ± SD of HC = 16.19 ± 1.32, p = 0.005) and TGF-β (Mean + SD of SSc = 150.8 ± 6.36, Mean ± SD of HC = 23.83 ± 0.93, p = 0.0001). We also detected several correlations between serum levels of the investigated proteins in patients with SSc. Conclusion: Along with TGF-β, our results show that miRNA-133, H19, and PKM2 seem to be potential contributors to SSc pathogenesis and could be promising biomarkers in the diagnosis of SSc patients. The lncRNA-H19 correlations with TGF- β, miRNA-133, and PKM2 suggest a possible influential effect of this RNA molecule on the pathogenesis of SSc.

Abstract Background People of Mediterranean descent are primarily affected by the autoinflammatory genetic condition known as familial Mediterranean fever (FMF). The disease is resistant to colchicine therapy in 10–20% of patients. Numerous recent animal studies showed promising results of extra virgin olive oil (EVOO) to control inflammation. The objective of this study was to assess the effectiveness of combining EVOO with colchicine in the treatment of colchicine-resistant familial Mediterranean fever (CRFMF) patients. Results Both the frequency of episodes and inflammatory indicators significantly decreased after a three-month course of daily EVOO treatment with colchicine. The average erythrocyte sedimentation rate (ESR) of patients was 78.6 mm/h before the EVOO administration, and it dropped to 27.8 mm/h, after that. Additionally, after taking EVOO, the mean serum amyloid A (SAA) decreased from 123.82 mg/dl to 59.78 mg/L. Also, the average C-reactive protein (CRP) decreased from 34.22 to 7.84 mg/dl following its administration; the mean nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) level decreased from 134.92 to 64.23 pg/ml. The mean caspase-1 level decreased from 7.8 to 4.98 ng/ml; and the mean levels of cytokines, interleukin 6 (IL-6), interleukin 1 beta (IL-1 β), and tumor necrosis factor-alpha (TNF-α) decreased from 9.8, 18.14, and 52.7 pg/ml, respectively, to 5.95, 12.51, and 29.39 pg/ml. Finally following the administration of EVOO, there was a notable overall improvement in the quality of life of (CRFMF) patients. Conclusion EVOO demonstrated a significant positive impact when paired with the tolerated dosage of colchicine in the management of CRFMF. Improvements were observed in both clinical and laboratory settings, including a reduction in the attack frequency and serum levels of inflammatory markers, such as NLRP3, caspase-1, ESR, CRP, IL-1β, IL-6, and TNF-α without any negative side effects.

Abstract Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has a high incidence of spread. On January 30, 2020, the World Health Organization proclaimed a public health emergency of worldwide concern. More than 6.9 million deaths and more than 768 million confirmed cases had been reported worldwide as of June 18, 2023. This study included 51 patients and 50 age- and sex-matched healthy subjects. The present study aimed to identify the expression levels of lncRNA CASC2 and miRNA-21-5p (also known as miRNA-21) in COVID-19 patients and their relation to the clinicopathological characteristics of the disease. The expression levels of noncoding RNAs were measured by RT-PCR technique. Results detected that CASC2 was significantly downregulated while miRNA-21-5p was significantly upregulated in COVID-19 patients compared to healthy subjects. A significant negative correlation was found between CASC2 and miRNA-21-5p. ROC curve analysis used to distinguish COVID-19 patients from controls. MiRNA-21-p serum expression level had a significant positive association with temperature and PO2 (p = 0.04 for each). These findings indicate that CASC2 and miRNA-21-p might be used as potential diagnostic and therapeutic biomarkers in COVID-19.

Background Vitiligo is an acquired depigmentary disorder characterized by destruction of melanocytes. The activity of vitiligo influences the clinical outcome and alters the choice of treatment modality. Intestinal fatty acid binding protein (I-FABP), also called FABP-2, is solely expressed in intestinal enterocytes of mammals. Objective To evaluate the serum and tissue levels of I-FABP in vitiligo patients and its relation to healthy controls. Patients and methods The present study is a case-control study that was carried out on 44 subjects subdivided into two equal groups, vitiligo, and matched controls. The clinical study was done as well and I-FABP levels in both serum and tissue were measured by Enzyme-linked immunosorbent assay (ELISA). Results There were significant elevations in I-FABP levels in both serum with a median of 7.16 and 5.29 (P=0.011) and in tissue with a median of 707.3 and 274.9 (P=0.014) for vitiligo patients in comparison with controls, respectively. Positive correlation between I-FABP levels in serum and in tissue was detected (r=0.488, P=0.021). Sensitivity for diagnosis vitiligo for serum and tissue I-FABP were 77.3 and 86.36%, respectively and specificity were 54.5 and 95.5%, respectively. Conclusion I-FABP can play a vital role in vitiligo and may be a marker that helps in early diagnosis of vitiligo, but it does not appear to be useful for determining vitiligo activity, severity.

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Several studies demonstrated the role of lncRNAs and miRNAs in the pathogenesis of preeclampsia; the aim was to detect the expression profiles of serum LncRNA ANRIL, miR-186, miR-181a, and MTMR-3 in patients with preeclampsia. The study included 160 subjects divided into 80 subjects considered as a control group, 80 patients with preeclampsia. We found that there was a significant difference between the preeclampsia and control groups with up-regulation of miR-186 median (IQR) = 4, 29 (1.35–7.73) (P

Psoriasis is a persistent inflammatory skin disorder driven by T cells. The disease is characterized by aberrant keratinocytes (KCs) differentiation, epidermal proliferation, and excessive hyperplasia of veins and arteries. The purpose of the study was to identify the levels of circulating lnc-HULC, miR-122, and Sirtuin 1 (SIRT-1) in psoriatic patients, evaluate their possible roles as diagnostic biomarkers, and link their levels with the development of metabolic syndrome during psoriasis progression. This study included 176 participants. The subjects were divided into four groups, with 44 participants in each group. All patients have undergone a complete history taking and clinical examination. Laboratory investigations included Low-density lipoprotein (LDL), High-density lipoprotein (HDL), Triglycerides (TG), Fasting blood sugar (FBS), and cholesterol plasma levels. Serum levels of miR-122 and lnc-HULC were examined by qRT-PCR. Serum levels of SIRT-1 were examined by ELISA. The serum concentrations of lnc-HULC and miR-122 were significantly higher in psoriatic participants compared to controls. Psoriatic patients' serum concentrations of SIRT-1 were much lower than those of healthy individuals. There was a negative association between SIRT-1 concentration and BMI, disease duration, PASI score, LDL, and cholesterol levels. The blood levels of lnc-HULC, miR-122, and SIRT-1 in psoriasis patients provide a promising role as diagnostic biomarkers in patients with and without metabolic syndrome.

Numerous malignancies, including colorectal and liver cancers, are ultimately more likely to occur in obese people, and chronic inflammatory conditions have been linked to this association. We are attempting to determine the clinical relevance of the mechanisms controlling the microRNA (miR-215 and miR-146a) expression and transforming growth factor-β (TGF-β)/interleukin-6 (IL-6) in a cross-link axis between obesity and colorectal cancer (CRC). Study participants were divided into four groups: healthy controls; obese without colorectal cancer; non-obese colorectal cancer; and obese with colorectal cancer. Obese and CRC patients had markedly higher expression of IL-6 and TGF-β, as well as tumor biomarkers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19.9 (CA19.9), and alpha-fetoprotein (AFP) levels. The relative expression of microRNAs (miR-215 and miR-146a) was significantly lower in obese patients with colorectal cancer. BMI and the microRNAs(miR-215 and miR-146a) showed a substantial negative correlation. TGF-β was favorably linked with IL-6, cholesterol, triglyceride levels, and BMI. High levels of TGF-β and IL-6 in the blood indicate how intensely inflammation develops in obesity, which could increase the risk of colorectal cancer.

Background: Thyroid hormones (THs) signaling has profound effects on many physiological processes. The regulation of THs signaling in various tissues involves the action of microRNAs (miRNAs) on thyroid deiodinases and receptors. THs regulate the expression of certain miRNAs and their target messenger RNAs (mRNAs) in various tissues and cells. The modulation of miRNA levels by THs affects their functions in processes such as liver lipid metabolism, skin physiology, and muscle and heart performance.Aim: This research aimed to investigate miR-181b, miR-206, and miR-21 in the serum of patients with subclinical and overt hypothyroidism to determine their possible role in the diagnosis of the disease and their relationship to clinical disorders related to hypothyroidism.Methods: This study included ninety participants, divided evenly into three groups as follows: patients with overt hypothyroidism diagnosed clinically, radiologically, and by investigation, subclinical hypothyroid patients, and healthy volunteers. The patients had a thorough medical history and underwent a clinical examination. Laboratory tests included plasma cholesterol, LDL, HDL, TGs, liver and renal function tests, CBC, fasting insulin, HOMA-IR, HbA1c, TSH, and free T4. The serum levels of miR-21, miR-206, and miR-181b were measured using qRT-PCR.Results: miR-206 and miR-181b levels were higher in the subclinical group, followed by the hypothyroid and control groups. For miR-21, there was a significantly lower mean value in both the hypothyroid and subclinical groups than in the control group, with no difference between the two groups. Both miR-206 and miR-181b showed a significant negative association with albumin and free T4 levels and a significant direct association with GGT, ALT, AST, creatinine, uric acid, TGs, TC, LDL, TSH, thyroid volume, and CAP score. The same correlation pattern was observed for miR-181b, except that it was not significantly correlated with the TGs. For miR-21 levels, there was a significant positive correlation with albumin, free T4 level, and kPa score and a negative correlation with GGT, ALT, AST, creatinine, uric acid, HOMA-IR, HbA1c, TC, LDL, TSH, and CAP score. Cases with F1 kPa score and S2 CAP scores had significantly higher averages for miR-206 and miR-181b, with a p-value of 0.05. Moreover, miR-21 levels were significantly lower in the S2 CAP score group.Conclusion: These miRNAs (miR-206, miR-181b, and miR-21) may be used as diagnostic biomarkers for hypothyroidism. They may be used as therapeutic targets to control dyslipidemia and hepatic steatosis during hypothyroid disease.

Background. Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma where red rash exists on the skin. Understanding the role of miRNAs and ncRNAs in p53-response has become an open discussion, as they can regulate p53 or its downstream targets, and ncRNAs themselves. Objectives. To evaluate the serum levels of NEAT-1, miR-34a, and p53 in MF patients and its relation to healthy controls to indicate whether it has a potential role in the pathogenesis of the disease. Subjects and Methods. This prospective case-control study was carried out on 75 subjects subdivided into two groups, 35 MF patients (stages 1 and II) and 40 matched healthy controls. Their clinical investigations and serum biomarkers (NEAT-1, miR-34a, and p53) were measured. Results. There were significant elevations in the expression levels of both NEAT-1 (5.10 ± 1.16) and p53 (277.28 ± 62.02) in the serum of MF patients in comparison with controls (1.01 ± 0.031) and (194.29 ± 16.039), respectively, while the level of miR-34a tends to decrease in MF patients (0.24 ± 0.15). There are no significant difference between MF stages and the level of miR-34a, while in NEAT-1 and p53, there are significant differences with p value

Abstract Background Colorectal malignant cells (CRC) are one of the world’s main causes of cancer mortality and morbidity. Notwithstanding the plenty of anti-CRC therapeutics, its prognosis remains not selective owing to cancer resistance to these therapeutics. Raloxifene (RX), a medication firstly used to treat osteoporosis, was recently licenced for the prevention of CRC. Unfortunately, due to medication resistance, many RX-based therapies are likely to become ineffective. Recently, we identified a novel method of administration to lengthen the half-life of RX by mixing it with chitosan (CS) and hyaluronic acid (HA). Thus, the rationale of the current study was to investigate how colon cancer cells were affected by RX-HA-CS nanoparticles (RX NPs) in terms of targetability, cytotoxicity, and epigenetic cascade alteration. Results RX NP had an entrapment efficiency (EE%) of 90.0 ± 8.12%. Compared to HCT 116 cells, Caco-2 cells were more susceptible to the cytotoxic effects of RX and its NP as well as they had a higher binding affinity to CD44 receptors compared to normal WI-38 cells. In comparison to the free RX, the RX NP’s cytotoxic fold changes in HCT 116 and Caco-2 cells were 2.16 and 2.52, respectively. Furthermore, the epigenetic cascade of some noncoding RNAs was examined. Moreover, particular protein concentrations were investigated in all tested cells after application of the proposed therapies. Our results showed that the RX NP recorded higher remarkable cytotoxic impact on CRC cells compared to the free RX. Intriguingly, it was hypothesized that RX nanoparticles attacked colon cancerous cells by up-regulating miR-944 and E-cadherin (ECN) expressions, while down-regulating the expressions of PPARγ, YKL-40, VEGF, H-19, LINC00641, HULC, HOTTIP, miR-92a, miR-200, and miR-21. Conclusions We may conclude that the RX NP effectively targets CRC cells in vitro via altering lncRNAs and miRNAs epigenetic cascade as well as cellular uptake through CD44-expressed CRC cells.

Background: Cerebrovascular stroke (CVS) is a potentially fatal disease. The most common risk factor for CVS is hypertension. Aim: While most studies in the field have focused on the functional roles of long noncoding RNAs (lncRNAs) NEAT1, GAS5, and HOTAIR in CVS, less attention has been paid to their clinical relevance to stroke incidence and prognosis. Also, a link has not yet been made between these lncRNAs and hypertension, our study aim was to investigate whether the expression of these lncRNAs differed between CVS with and without hypertension, as well as to compare each group to controls. Method: In total, 181 CVS patients were enrolled, including 91 chronic hypertensive patients with stroke, 90 stroke patients without hypertension, and 51 control subjects. blood samples were collected on the day of recruitment from patients with CVS and controls. Real-time qRT-PCR was used to detect the expression of target lncRNAs in serum. Results: When compared to controls, there was a statistically higher level of lncNEAT1 in each case group (median (IQR) = 3.68 (1.35–7.35) and 3.05 (0.95–6.45) for the hypertensive and non-hypertensive groups, respectively, with a significantly higher level in the hypertensive group (P = 0.04). When compared to controls, lncHOTAIR was significantly downregulated in all case groups (medians in hypertensive and non-hypertensive patients were 0.13, and 0.34, respectively), with a significantly lower level in the hypertensive group (P = 0.05). LncGAS5 levels in patients were significantly lower (median (IQR) = 0.16 (0.02–0.55) and 0.25 (0.03–0.99) for the hypertensive and non-hypertensive groups, respectively) compared to controls, with a significantly lower level in the hypertensive group (P = 0.02). There was a significant positive correlation between NEAT1 and GAS5, but a significant negative correlation between each with HOTAIR in both patients' groups. We also detected a significant negative correlation between each NEAT1 or GAS5 and NIHSS score while a significant positive correlation between HOTAIR and NIHSS. ROC curve analysis for GAS5 was able to differentiate patients with CVS hypertensive from patients with CVS non-hypertensive. Conclusion: Patients in each case group had statistically higher levels of NEAT1 and lower levels of HOTAIR and GAS5 compared to control levels, with higher significant NEAT1 but lower significant HOTAIR and GAS5 in the hypertensive group. Therefore, lncRNAs NEAT1, HOTAIR, and GAS5 could be used as diagnostic and prognostic biomarkers of CVS that correlate with NIHSS score and could produce a novel target for CVS therapy.

Abstract The genetic and epigenetic architecture of clinical and subclinical hypothyroidism remains unclear. We investigated the impact of long noncoding RNA (LncRNA)-PAX8-AS1 and LAIR-2 genetic variants on the susceptibility to clinical and subclinical hypothyroidism, their influence on LncRNA-PAX8-AS1 and LAIR-2 expression and their potential as hypothyroid biomarkers. Hundred clinical hypothyroid patients, 110 subclinical hypothyroid patients, and 95 healthy controls were enrolled. Gene expression analysis and genotyping were performed by qPCR. LAIR-2 protein, a proinflammatory mediator, was tested by ELISA. Serum LncRNA-PAX8-AS1 was downregulated, whereas LAIR-2 mRNA and protein levels were upregulated in clinical and subclinical hypothyroid patients compared to healthy controls. LncRNA-PAX8-AS1 rs4848320 and rs1110839 were associated with increased risk of clinical hypothyroidism. Interestingly, both SNPs were associated with differential expression of serum LncRNA-PAX8-AS1 among clinical hypothyroid patients. LAIR-2 rs2287828 was associated with elevated risk of both clinical and subclinical hypothyroidism. Harboring the rs2287828 T allele augmented the LAIR-2 mRNA expression among clinical hypothyroid patients, while elevated both LAIR-2 mRNA and protein levels in subclinical hypothyroid patients. The rs4848320-rs1110839-rs2287828 TTT, CTT, and CGT haplotypes were associated with increased hypothyroid risk. Surprisingly, serum LncRNA-PAX8-AS1 and LAIR-2 mRNA expression demonstrated superior diagnostic accuracy for clinical hypothyroidism and turned out as independent predictors in the multivariate analysis. Conclusively, LncRNA-PAX8-AS1 and LAIR-2 genetic variants are novel genetic biomarkers of hypothyroidism that could alter the LncRNA-PAX8-AS1 and LAIR-2 expression. LncRNA-PAX8-AS1 and LAIR-2 expression profiles have the potential as effective diagnostic and prognostic indicators of hypothyroidism.

Abstract Introduction Essential oils (EOs) are complex structures and possess several pharmacological effects. Nanomedicine offers a solution for their major limitations, including poor solubility, volatility, and non–controlled release, preventing their clinical use. Methods Here, we developed a novel delivery system by nanoformulations that were prepared by impregnating savory essential oil (SA) into mesoporous silica nanoparticles (MSNs). The nanoformulations were characterized and examined for their anticancer activities on cancer cells (HepG2 liver and HL60 leukemia cells) and MRC5 normal cells. We further tested the mechanisms of action and possible molecular targets against HL60 cells. Results The results demonstrated that SA was governed by nanoformulations under the dual–trigger release of pH/glutathione, and it typically fit the Korsmeyer–Peppas kinetic model. The nanoformulations enhanced the anticancer effect against HepG2 cells and HL60 cells compared to SA but were less cytotoxic to MRC5 normal cells and regulated various molecular pathways of apoptosis. Most importantly, new results were obtained on the genetic regulation principle through the high inhibition of long noncoding RNAs (HOTAIR, HULC, CCAT1, and H19) and matrix metalloproteinases (MMP–2 and MMP–9), providing a novel leukemia target. Conclusions These results suggest potential impacts for nanoformulations composed of SA with a sustained release pattern controlled by dual–trigger release of pH/GSH that enhanced anticancer cells. This approach may offer a new route for using EOs as new targets for cancers and open the door for deep preclinical investigations.

Key points 1. MIR146A (C allele) had a protective role in rheumatoid arthritis association. MTMR3 was associated with rheumatoid arthritis using the dominant, Co-dominant heterozygote and recessive models. MIR499/MIR499A had no association with rheumatoid arthritis.

Objective: RNA-based mechanisms of epigenetic modification related to acute ischemic stroke (AIS) have been widely studied recently. The current work aimed to determine the potential roles of four ncRNAs (TUG1 and its target miR-21, NBAT1, and miR-335) as promising diagnostic biomarkers in AIS as well as their involvement in the disease pathogenesis.Methods: The levels of the studied lncRNAs and miRNAs were measured in the serum for two different groups, including patients with AIS (60) and healthy controls (60). All individuals were subjected to a full history investigation and clinical examination. Blood samples were tested for FBS, 2HPP, TAG, HDL, LDL, TSH, T3, and T4 levels.Results: The serum levels of TUG1 were significantly increased in AIS patients compared to control subjects. It is worthwhile to note that serum TUG1 levels were positively correlated with cholesterol, triglycerides, LDL, carotid IMT (Intima-media thickness), and miR-21, while they were negatively correlated with HDL levels. Our study showed that NBAT1 serum expression levels were elevated in AIS patients compared to controls. NBAT1 expression levels were observed to be positively correlated with triglycerides, TUG1, and miR-21. NBAT1 could distinguish between AIS patients and controls with a sensitivity of 100% and specificity of 100% at a cut-off point of 1.45. Regarding miR-335, we found that its expression levels were downregulated in AIS patients compared with healthy controls. It could distinguish between AIS patients and controls with a sensitivity of 73.3% and a specificity of 100% at a cut-off point of 0.796.Conclusion: Our results revealed that serum TUG1, miR-21, NBAT1, and miR-335 could be promising molecular diagnostic markers for AIS as these biomarkers could discriminate between AIS patients and healthy controls.

Background: Ischemic stroke is one of the serious complications of diabetes. Non-coding RNAs are established as promising biomarkers for diabetes and its complications. The present research investigated the expression profiles of serum TUG1, LINC00657, miR-9, and miR-106a in diabetic patients with and without stroke.Methods: A total of 75 diabetic patients without stroke, 77 patients with stroke, and 71 healthy controls were recruited in the current study. The serum expression levels of TUG1, LINC00657, miR-9, and miR-106a were assessed using quantitative real-time polymerase chain reaction assays.Results: We observed significant high expression levels of LINC00657 and miR-9 in the serum of diabetic patients without stroke compared to control participants. At the same time, we found marked increases of serum TUG1, LINC00657, and miR-9 and a marked decrease of serum miR-106a in diabetic patients who had stroke relative to those without stroke. Also, we revealed positive correlations between each of TUG1, LINC00657, and miR-9 and the National Institutes of Health Stroke Scale (NIHSS). However, there was a negative correlation between miR-106a and NIHSS. Finally, we demonstrated a negative correlation between LINC00657 and miR-106a in diabetic patients with stroke.Conclusion: Serum non-coding RNAs, TUG1, LINC00657, miR-9, and miR-106a displayed potential as novel molecular biomarkers for diabetes complicated with stroke, suggesting that they might be new therapeutic targets for the treatment of diabetic patients with stroke.

Background: Breast cancer (BC) patients have a higher chance of survival if it is diagnosed at an early stage, which is essential for efficient treatment of the condition. The results of an elevated risk of cancer, including BC, previously associated with the ins/del polymorphism rs145204276 in the promoter region of growth arrest-specific 5 (GAS5) are still up for debate. Thus, this study aimed to appraise the frequency of the GAS5 rs145204276 variant with BC risk and demonstrate the potential impact of the sirtuin 1 (SIRT-1), transforming growth factor-beta (TGF-β), and microRNA-182 (miR-182) expression and their diagnostic value in BC. Methods: Blood samples of 155 patients with BC and fibroadenoma and 80 healthy controls were analyzed for GAS5 rs145204276 single nucleotide polymorphism (SNP), SIRT-1, TGF-β, and miRNA-182 expression levels. Results: Ins/ins genotype and ins allele frequencies for GAS5 rs145204276 were considerably higher in BC patients compared with controls. Patients with BC had significantly greater serum levels of TGF-β, miR-182, and SIRT-1 expression. Conclusions: The SIRT-1, TGF-β, and miR-182 genes provide novel, noninvasive diagnostic biomarkers for BC.

BackgroundThe SARS-CoV-2 virus's frequent mutations have made disease control with vaccines and antiviral drugs difficult; as a result, there is a need for more effective coronavirus drugs. Therefore, detecting the expression of various diagnostic biomarkers, including ncRNA in SARS-CoV2, implies new therapeutic strategies for the disease.AimOur study aimed to measure NEAT-1, miR-374b-5p, and IL6 in the serum of COVID-19 patients, demonstrating the correlation between target genes to explore the possible relationship between them. Also, the association between target genes and patients' clinical findings and radiological severity indices will be explored.Patients and methodsThe current study included 48 COVID-19-infected individuals and 40 controls. Quantitative real-time PCR (qPCR) was performed to detect lncRNA NEAT-1 and miRNA374b-5p fold change (FC) in the participants' sera. Enzyme-Linked Immune Sorbent Assay (ELISA) is used to detect IL6.ResultsOur results showed statistical significance with lower levels of (NEAT-1) [ median (range) = 0.08 (0.001-0.602)], and (miR374b-5p) [ median (range) = 0.14 (.01-7.16)] while higher IL-6 levels [ median (range) = 41.3 (7.2-654) pg/ml] when compared to controls with p-value ConclusionsOur study is the first to detect decreased NEAT-1 and miR374b-5p expression in COVID-19 patients' serum. There was also an increase in IL6 levels. There is a negative correlation between NEAT-1 and IL6 in COVID-19 patients.

Background Psoriasis is a chronic, inflammatory, T-cell-mediated autoimmune disease. Vitiligo is an acquired depigmentary disease that occurs due to the loss of functional melanocytes from the epidermis. Interleukin (IL)-9 is a T cell-derived cytokine that was initially designated as a T helper2 cytokine. There is a link between the expression and action of IL-9 and pro-inflammatory cytokines tumor necrosis factor, IL-1, IL-17, and interferon-γ, suggesting that IL-9 is associated with the pathogenesis of autoimmune diseases. Objective To evaluate the tissue levels of IL-9 in patients with psoriasis and vitiligo in comparison with controls, to assess the possible role of IL-9 in the pathogenesis of these diseases. Patients and methods This case–control study included 30 patients with psoriasis, 30 patients with vitiligo, and 30 age-matched and sex-matched healthy controls. A skin biopsy was taken from all participants for evaluation of tissue IL-9 levels by enzyme-linked immunosorbent assay. Results Tissue IL-9 was significantly higher in patients with psoriasis (28.65±18.456) and patients with vitiligo (51.056±41.536) than controls (P=0.013 and P