Combined microneedling with topical vitamin D3 or bimatoprost versus microneedling alone in the treatment of alopecia areata: A comparative randomized trial.

INTRODUCTION: Alopecia areata (AA) is a challenging disease with variable treatment outcomes. Hair follicles express vitamin D receptors. Therefore, vitamin D3 may be promising for AA treatment through immunomodulatory mechanisms. The efficacy of bimatoprost in scalp AA treatment was reported by few studies. OBJECTIVE: To evaluate the efficacy and safety of microneedling (MN) with topical vitamin D3 versus MN with bimatoprost in comparison with MN alone in the treatment of localized AA. PATIENTS AND METHODS: Seventy-five patients with localized AA were divided into three groups. The first group: 25 patients were treated with MN alone. The second group: 25 patients treated with MN combined with topical vitamin D3. The third group: 25 patients treated with MN combined with bimatoprost solution. The response was evaluated clinically and dermoscopically. RESULTS: At the end of the study, all groups showed a statistically significant decrease in the SALT score compared to the baseline. The clinical response (regrowth scale): vitamin D and bimatoprost groups showed a statistically significant higher regrowth scale compared to MN alone group (p-value = 0.000). After treatment, hair regrowth was significantly higher in MN combined with bimatoprost than in MN combined with topical vitamin D3. However, after 3 months of follow-up, there was no statistically significant difference between both groups. Side effects were mild and transient in all groups. CONCLUSION: Topical vitamin D3 and bimatoprost combined with MN are safe and effective therapeutic options for localized AA.

MiR-146a and miR-155 polymorphisms in Egyptian patients with Behcet's disease.

Introduction: The current study was designed to analyze whether polymorphisms of miR-146a and miR-155 are related to Behçet's disease (BD) in the Egyptian population. Material and methods: A total of 96 unrelated BD patients and 100 healthy subjects were genotyped for miR-146a (rs2910164) and miR-155 (rs767649) using real-time polymerase chain reaction. Results: The results showed significant elevation in the frequency of rs2910164 GG and CC genotypes in BD patients compared with controls (adjusted OR = 22.156, 95% CI: 4.728-103.818; p < 0.001 and adjusted OR = 40.358, 95% CI: 8.928-182.440; p < 0.001, respectively). Also, the rs2910164 G allele conferred a higher risk of developing BD (adjusted OR = 3.665, 95% CI: 2.013-6.671; p < 0.001). MiR-146a (rs2910164) polymorphism was a risk factor for susceptibility to BD in dominant, recessive and additive models of inheritance (all p < 0.001), while the miR-155 (rs767649) polymorphism was a risk factor in the recessive model only (p = 0.021). GG and CG genotypes of rs2910164 were associated with higher Behcet's disease current activity index (BDCAI) and ocular involvement compared with CC genotype (p = 0.005 and p = 0.004, respectively). Genotype AT of rs767649 was related to higher BDCAI (p = 0.026) compared with TT and AA genotypes. Conclusions: miR-146a (rs2910164) and miR-155 (rs767649) are likely to play an important role in the Egyptian population in development of BD and also influence disease severity.

Comparative study between fractional carbon dioxide laser versus retinoic acid chemical peel in the treatment of acanthosis nigricans.

BACKGROUND: Acanthosis nigricans (AN) is a common dermatological issue with several therapeutic modalities to treat. Despite retinoid is the first drug of choice in the treatment, the fractional-ablative carbon dioxide (CO2 ) laser has revealed as a promising procedure for the management of neck-AN, outstanding to its ability for superficial ablation of the skin surface, with trans-epidermal melanin elimination. OBJECTIVES: To decide whether fractional-ablative CO2 laser or retinoic acid (5%) peel is the more effective and safe choice for AN treatment. METHODS: In this study, twenty Egyptian cases with neck-AN were enrolled, where each case was exposed to four sessions with 2 weeks apart of both fractional CO2  laser on the right half of the neck and retinoic acid peel on the left half of the neck. Cases were assessed by a scoring system: Acanthosis Nigricans Area and Severity Index (ANASI) score, two blinded dermatologists, and dermoscopically before and one month after treatment. RESULTS: We found a highly statistically significant improvement among both treated groups regarding (ANASI) score and dermatologist's assessments. Bedside, the degree of sulci cutis, cristae cutis, brown-to-dark brown dots, and milia-like cysts, dermoscopic sign improvement was evident in both treated groups. However, fractional CO2 laser shows the superior result to retinoic acid peel in the treatment. CONCLUSION: Fractional CO2 laser and retinoic acid peel are considered effective modalities for neck-AN treatment. However, fractional CO2 laser was more effective.

Vortioxetine mitigates neuronal damage by restricting PERK/eIF2α/ATF4/CHOP signaling pathway in rats subjected to focal cerebral ischemia-reperfusion.

AIMS: Stroke has risen to the fifth and third most common causes of death in the United States and the rest of the world, respectively. Vortioxetine (VTX) is a multimodal antidepressant agent that balances 5-HT receptors and represses the serotonin transporter. Our study aimed to examine the neuroprotective impacts of VTX against cerebral ischemia caused by occluding the middle cerebral artery (MCA). MAIN METHODS: Until the middle cerebral artery occlusion (MCAO) induction, VTX (10 mg/kg/day) was taken orally for 14 days. Behavioral assessments were carried out 24 h after the MCAO technique. The hippocampal and cortical tissues of the brain were isolated to assess the histological changes and the levels of the biochemical parameters. KEY FINDINGS: MCAO damage led to severe neurological deficits and histopathological damage. However, VTX improved MCAO-induced neurological deficits and ameliorated histopathological changes in both hippocampal and cortical tissues of MCAO rats. Western blot analysis showed increments of p-PERK, CHOP, ASK-1, NICD, HES-1, HES-5, and p-eIF2α expression levels in MCAO rats. Moreover, ELISA revealed an increase in the levels of ATF4, IRE1, Apaf-1, and HIF-1α, while VTX administration ameliorated most of these perturbations induced after MCAO injury. SIGNIFICANCE: This research suggests that VTX could be a potent neuroprotective agent against ischemic stroke by inhibiting a variety of oxidative, apoptotic, inflammatory, and endoplasmic reticulum stress pathways.

The Influence of rs1859168 Polymorphism on Serum Expression of HOTTIP and Its Target miR-615-3p in Egyptian Patients with Breast Cancer.

BACKGROUND: Polymorphisms of long noncoding RNAs are lately documented as hazardous factors for the development of numerous tumors. Furthermore, the evaluation of noncoding RNAs has emerged as a novel detector of breast cancer patients. We aimed to genotype the HOXA transcript at the distal tip (HOTTIP) rs1859168 and assess its relationship with the levels of the serum HOTTIP and its target miR-615-3p in patients with breast cancer (BC). METHODS: One hundred and fifty-one patients with BC, 139 patients with fibroadenoma (FA), and 143 healthy participants were incorporated into the current study. The genotyping of rs1859168 and the measurements of the HOTTIP and miR-615-3p levels were assessed using quantitative real-time PCR. RESULTS: We revealed a significant association between each of the CC genotypes, C allele, dominant and recessive models, and the increased risk of BC (p = 0.013, p < 0.001, p < 0.001, and p < 0.001, respectively) relative to the healthy controls. Similarly, the CC genotype, C allele, and recessive model were observed to be related to the increased incidence of BC with respect to FA (p < 0.001 for all). A significant upregulation of HOTTIP and a marked decrease of miR-615-3p were verified in patients with BC compared to each of the healthy individuals, patients with FA, and the non-BC group (healthy subjects + FA) (p < 0.001 for all). A significant negative correlation was demonstrated between the expression of HOTTIP and miR-615-3p in the serum of patients with BC. The HOTTIP expression was upregulated, while that of miR-615-3p was downregulated in patients with BC who carried the CC genotype with respect to those who carried the AA or AC genotypes (p < 0.05 for all). CONCLUSIONS: The genetic variants of rs1859168 are linked to an increased susceptibility to BC. Moreover, HOTTIP and miR-615-3p may be used as novel indicators and targets for the treatment of patients with BC.

Differential Expression of Serum TUG1, LINC00657, miR-9, and miR-106a in Diabetic Patients With and Without Ischemic Stroke.

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.

Analysis of the expression profile of long non-coding RNAs MALAT1 and THRIL in children with immune thrombocytopenia.

BACKGROUND/AIMS: Pediatric immune thrombocytopenia (ITP) is an autoimmune disease; whose etiology is not exactly understood and seems to be highly multifactorial. Long non-coding RNAs (lncRNAs) are key regulators of different actions, which contribute to the development of many autoimmune diseases. To gain a further understanding, we estimated the relative expression of lncRNAs Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and tumor necrosis factor-α (TNF-α) and heterogeneous nuclear ribonucleoprotein L (hnRNPL) immune-regulatory lncRNA (THRIL) in pediatric ITP. METHODS: In this case-control study, analysis of the expression profiles of these lncRNAs in blood samples from children with ITP and healthy controls (HCs) using quantitative real-time PCR was done. The association of MALAT1 and THRIL with ITP clinical features and their potential usage as non-invasive circulating biomarkers for ITP diagnosis was also evaluated. The receiver operating characteristic curve was constructed, and an area under the curve was analyzed. RESULTS: Both lncRNAs MALAT1 and THRIL were significantly upregulated in ITP patients in comparison to HCs ( p < .0001 and = .001 respectively). In addition, there was a positive significant correlation between the expression level of both biomarkers among patients (r = 0.745, p < .0001). At cutoff points of 1.17 and 1.27 for lncRNAs MALAT1and THRIL, respectively, both biomarkers had an excellent specificity (100% for both) and fair sensitivity (63.6 and 73.3% for lncRNAs MALAT1and THRIL, respectively). Improvement of biomarkers specificity was obtained by evaluation of the combined expression of both biomarkers. Serum lncRNAs MALAT1 and THRIL could be used as potential biomarkers in differentiating childhood ITP patients and HCs.

Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent form of cancer. Various long non coding RNA (lncRNAs) and micro RNA have been confirmed to have a role in the progression of HCC. Our aim was to investigate for the first time the expression profile of serum level of LNC NEAT (nuclear enrich abundant transcript) and MiR-129-5p in HCC patients and their relations with patient's clinical and biochemical investigations rather than previous studies on tissue cell lines. Our study includes 72 subjects divided into 36 as control subjects and 36 patients with HCC. Complete physical and laboratory investigations were done on all subjects. RNAs were extracted from sera of all subjects. RNAs were reversed transcribed into cDNAs using Qiagen, Valenica, CA. Quantitative PCR (qPCR) was performed using Rotor gene Q System (Qiagen). Relative NEAT1 expression level was significantly increased in serum of HCC patients 4.7 (1.31-6.82) (p < .0001). Meanwhile MiR-129-5p relative expression level was significantly decreased in serum of HCC patients 0.17 (0.14-20) (p < .0001). Also there was negative significant correlation between the expression level of LNC NEAT and MiR-129-5p in HCC group (p < .0001). ROC curve analysis revealed that LNC NEAT; AUC = 0.981, p < .0001, cutoff value (1.02), sensitivity 100%, specificity 88.9%. MiR-129-5p; AUC = 0.997, p < .0001, cutoff value (0.43), sensitivity 100%, specificity 97.2%. Serum LNC NEAT and MiR-129-5p could be used as potential biomarkers for HCC cancer diagnosis and prognosis.

Analgesic Potentials of Preoperative Oral Pregabalin, Intravenous Magnesium Sulfate, and their Combination in Acute Postthoracotomy Pain.

OBJECTIVES: The objective of this study was to investigate the effects of the preoperative combination of oral Pregabalin and intravenous (IV) magnesium sulfate as analgesic adjuvants in postthoracotomy pain. PATIENTS AND METHODS: One hundred twenty patients with American Society of Anesthesiologists physical status II were allocated randomly into 1 of 4 groups. Group MP received 300 mg pregabalin orally and an IV infusion of magnesium sulfate 50 mg/kg mixed with 200 mL normal saline (NS); group P received 300 mg pregabalin orally and 200 mL NS infusion; group M received an IV infusion of magnesium sulfate 50 mg/kg mixed with 200 mL NS and a placebo capsule; and group C received placebo capsule and an IV infusion of 200 mL NS. All medications were given 1 hour before surgery in all groups. In the first 24 hours postoperatively, total morphine consumption, the Visual Analog Scale (0 to 10)-used as a pain measurement tool-and postoperative nausea and vomiting were assessed. RESULTS: The total morphine consumption in the first 24 hours postoperatively decreased significantly in group MP (28.47±5.76 mg) compared with group P (33.97±6.34 mg), group M (40.87±4.4 mg), and group C (42.2±6.1 mg), respectively. VAS scores were in the accepted range (≤4) in the 4 groups throughout the first 24 hours, as all patients were on patient-controlled analgesia. However, there was a statistically significant difference at 0 and 4 hours postoperatively in favor of groups MP and P. Postoperative nausea and vomiting decreased significantly in groups MP, P, and M in comparison with group C (P<0.001). CONCLUSIONS: The combined preoperative single dose of pregabalin and magnesium sulfate is an effective method for attenuating postoperative pain and total morphine consumption in patients undergoing thoracotomy.

Comparative study between: Carboxytherapy, platelet-rich plasma, and tripolar radiofrequency, their efficacy and tolerability in striae distensae.

BACKGROUND: Striae distensae are very common cutaneous disorders that produce great psychological stress for women. OBJECTIVE: measure and compare between efficacy and tolerability of three modalities for treatment of striae distensae. PATIENTS AND METHODS: Forty-five female patients with striae distensae were randomly selected from the outpatient dermatology clinics of Al-Zahra university Hospital within 6 months period. Patients divided into three groups according to the therapeutic modalities were used. Group A: treated with carboxytherapy using carbon dioxide (CO2) injection, Group B: where patients were treated with intradermal injection of autologous platelet-rich plasma (PRP), and Group C: where we used tripolar radiofrequency (RF) for treatment. RESULTS: All treated groups showed overall clinical improvement as regards the width, texture, and overall improvement after treatment (P > .05), with no statistically significant differences between the three groups. Patient's satisfaction was statistically significantly better in both group C (93.33%) and group A (80%) while group B (53.33%) was less with minimal side effects such as pain and ecchymosis, which were more frequent in group B than the other two groups; but with no statistically significance differences both groups A and C were effective with no significant differences in both types of striae and in any site of the body but group B is significantly more effective on striae rubra on trunk, with better improvement of lesions texture. CONCLUSION: The three modalities of treatments proved to be effective clinically and histopathologically in treating both types of striae, which were well tolerated by the patients with minimal, transient side effects and our study results gave us guidelines for their clinical application.

Treatment of periorbital dark circles: Comparative study of carboxy therapy vs chemical peeling vs mesotherapy.

OBJECTIVE: Evaluation and comparison of the efficacy and safety of 3 different modalities of treatment for dark circles that function via different modes of action. METHODS: In total, 45 female patients with periorbital hyperpigmentation were randomly selected to participate from those attending the outpatient dermatology clinic of Al-Zahraa University Hospital within a 6-month period. Patients were divided into 3 groups, and the groups were subjected to different types of therapy: group A, carboxy therapy; group B, chemical peel; and group C, vitamin C mesotherapy. RESULTS: No statistically significant differences were detected in improvements in pigmentation or the degree of patient satisfaction between any of the groups. However, the mesotherapy group reported more of a burning sensation following treatment than the other 2 groups but also showed a significant improvement in pigmentation and patient satisfaction compared with the carboxy group. CONCLUSION: All 3 treatment modalities were effective in the reduction in periorbital pigmentation. However, mesotherapy showed a significant improvement in pigmentation and a higher level of patient satisfaction compared with the other types of treatment.

LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis.

Long non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.

Association of MicroRNA-155rs767649 Polymorphism with Susceptibility to Preeclampsia.

Preeclampsia (PE) is a multifactorial disorder. Several studies showed that micro RNAs may play a critical role in PE pathogenesis. We aimed to investigate for the first time the association of mir-155rs767649 polymorphism with PE. Eighty patients with preeclampsia and 80 normal subjects were enrolled in the study. Serum expression levels of mature mir-155were evaluated using real-time PCR, and mir-155 rs767649 (T/A) polymorphism was genotyped using TaqMan SNP genotyping. There was a significant difference between the expression level of mir-155 in cases (5.86 ± 3.11) in comparison with controls (0.58 ± 0.30) (P<0.0001). Also,the minor allele of rs767649 was significantly associated with increased risk of PE [Recessive model: adjusted Odds ratio (OR) = 5.240, 95% confidence interval (CI) = (1.999-13.733),P= 0.001]. There was a significant difference between different genotypes according to expression levels of mir-155 in PE (P<0.0001) with high expression levels in TA genotype (7.10 ± 3.11 ). Mir-155 may play a critical role in PE pathogenesis. The obtained data suggest that a minor allele of rs767649 might be a predisposing factor for PE.

The anti-inflammatory and anti-fibrotic effects of tadalafil in thioacetamide-induced liver fibrosis in rats.

Liver fibrosis is a health concern that leads to organ failure mediated via production of inflammatory cytokines and fibrotic biomarkers. This study aimed to explore the protective effect of tadalafil, a phosphodiesterase-5 inhibitor, against thioacetamide (TAA)-induced liver fibrosis. Fibrosis was induced by administration of TAA (200 mg/kg, i.p.) twice weekly for 6 weeks. Serum transaminases activities, liver inflammatory cytokines, fibrotic biomarkers, and liver histopathology were assessed. TAA induced marked histopathological changes in liver tissues coupled with elevations in serum transaminases activities. Furthermore, hepatic content of nitric oxide and tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta were elevated, together with a reduction of interleukin-10 in the liver. In addition, TAA increased hepatic contents of transforming growth factor-beta, hydroxyproline, alpha-smooth muscle actin, and gene expression of collagen-1. Pretreatment with tadalafil protected against TAA-induced liver fibrosis, in a dose-dependent manner, as proved by the alleviation of inflammatory and fibrotic biomarkers. The effects of tadalafil were comparable with that of silymarin, a natural antioxidant, and could be assigned to its anti-inflammatory and anti-fibrotic properties.

Combined treatment with fractional carbon dioxide laser, autologous platelet-rich plasma, and narrow band ultraviolet B for vitiligo in different body sites: A prospective, randomized comparative trial.

BACKGROUND: Multiple treatment options are introduced in treatment of vitiligo but the response is unsatisfactory. OBJECTIVE: In this prospective, randomized, comparative trial, we studied the effect of combined treatment with fractional carbon dioxide (CO2 ) laser, platelet-rich plasma (PRP) injection, and narrowband ultraviolet B (NB-UVB) for stable nonsegmental vitiligo regarding repigmentation grade, patient's satisfaction, and side effects. METHODS: Eighty adult patients with localized nonsegmental vitiligo were enrolled in this study. The patients were randomly categorized to receive 4 lines of treatment; fractional CO2 laser, PRP, combined fractional CO2 laser and PRP, and combined fractional CO2 laser and NB-UVB. The treatment period was 2 months. Patients were clinically evaluated 3 months after the last treatment. Outcome was evaluated by 5-point scale for repigmentation, 10-point visual analog scale for patient's satisfaction, and side effects. RESULTS: Laser and PRP group achieved the best results regarding repigmentation and patient's satisfaction. Sixty percent of the patients developed repigmentation >50% and 40% of patients developed repigmentation >75%. In laser and NB-UVB group, 5% developed repigmentation >75% and 25% developed repigmentation >50%. Only 10% of patients developed repigmentation >75% in laser group and only 20% of patients developed repigmentation >75% in PRP group. CONCLUSIONS: Combination of fractional CO2 laser with PRP injection is a promising treatment for vitiligo, followed by combination of fractional CO2 laser with NB-UVB phototherapy. Both fractional CO2 laser and PRP injection gave poor results if they received alone.