Examining the correlation of lymphangiogenesis biomarkers with clinical condition in Age-Related Macular Degeneration (AMD).

The aim of this study is to investigate the relationship between age-related macular degeneration (AMD) and lymphangiogenesis biomarkers, namely LYVE-1, Podoplanin, VEGF-C, VEGFR-2 and VEGFR-3. This prospective and interventional study includes 30 patients with AMD which may be dry or wet type and 30 controls for whom vitrectomy and phacoemulsification was indicated due to additional pathologies (epiretinal membrane, macular hole, retinal detachment, and cataract). 0.1-0,2 ml of aqueous humor and 0.5-1 ml of vitreous sample was taken during the operations. Before the operations 1 tube serum was also taken. All the lymphangiogenesis biomarkers in the study are examined by ELISA method. LYVE-1 (p = 0.001) and Podoplanin (p = 0.004) levels in the vitreous for the patient group are found to be significantly lower than the control group. Serum (p = 0.019), vitreous (p = 0.001), aqueous (p < 0.001) levels of VEGF-C for the patient group are significantly higher than the control group. VEGF-C/VEGFR-2 (p < 0.001), VEGF-C/VEGFR-3 (p < 0.001) ratios in the vitreous for the patient group are found to be significantly higher than the control group. Especially in wet AMD patients, LYVE-1 level is significantly lower in the vitreous (p = 0.002) and aqueous (p = 0.002) than the control group. In addition, Podoplanin level is observed as significantly lower in the vitreous (p = 0.014) and serum (p = 0.002) in comparison to control group. In the wet AMD group, VEGF-C level in the vitreous (p < 0.001), aqueous (p < 0.001) and serum (p = 0.001) is higher than the control group. The result of this study indicates a valid relationship between the weakening of lymphangiogenesis and the pathophysiology of AMD, especially for the wet type. It is observed that the levels of receptors that bind VEGF-C (VEGFR-2 and VEGFR-3) do not increase at the same rate as VEGF-C to compensate for the increase in VEGF-C. The absence of an increase in VEGFR-3, which is especially necessary for lymphangiogenesis, also suggests that lymphangiogenesis is weakened or decreased in AMD. In the future interventional studies with larger series, examination of lymphangiogenic biomarkers in inflammatory retinal diseases and glaucoma may reveal unexplored details.

Predictors of Significant Histological Hepatic Abnormality in Treatment-Naive Patients Infected with HBeAg-Negative Chronic Hepatitis B.

Objective: This study aimed to determine the predictors for significant hepatic abnormality (SHA), a treatment indication, by assessing demographic, laboratory, and radiological results of chronic hepatitis B (CHB) patients who underwent liver biopsy. Materials and Methods: In this retrospective study, individuals with untreated hepatitis B e-antigen (HBeAg)-negative CHB infection were enrolled. Multivariate analysis modeling was conducted with parameters identified as predictors for SHA in univariate analysis. Optimal threshold levels for variables to predict SHA in patients with chronic hepatitis B were determined based on receiver operating characteristic (ROC) curve analysis. Results: A total of 566 patients with untreated chronic hepatitis B were included in the cohort; 61% (345/566) were male, and the median age was 41 years (interquartile range [IQR]=34-50). Notably, 36.9% (209/566) had SHA. In the multivariate analysis, utilizing different models, age, gender, HBV-DNA, LDL, ALT, and platelet count were identified as the most reliable predictors for SHA in CHB patients. For predicting SHA, the area under the ROC curve values of HBV-DNA, AST, and ALT were 0.704 (sensitivity=62.8%, specificity=76.2%; p<0.0001), 0.747 (sensitivity=51.9%, specificity=88.9%; p<0.0001), and 0.737 (sensitivity=68.6%, specificity=68.4%; p<0.0001), respectively. Conclusion: In our study, age, male gender, ALT, AST, HBV-DNA, LDL cholesterol, platelet count, and FIB-4 score were independent predictors of SHA in HBeAg-negative chronic hepatitis B. The most sensitive parameters for SHA were LDL and ALT. The most specific parameters were age, AST, and APRI score. SHA may occur in patients with high HBV-DNA levels, even if ALT values are normal in HBeAg-negative patients.

Independent predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B.

OBJECTIVE: There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection. METHODS: All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records. RESULTS: A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors. CONCLUSION: Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.

Liposomal formulations of Oleae europaea L.: analyzing the antioxidant and antidiabetic activities along with toxicity profile in pancreatic beta TC6 cell line.

Olea europaea L. (Oleaceae), is rich in phenolic content and has powerful antioxidant and antidiabetic activity. However, there are no medicinal products prepared due to this feature. Therefore, this study aims to characterize an O. europaea extract with strong antioxidant and antidiabetic properties and to prepare nanoformulations containing this extract. To determine the activities of the extracts prepared from the leaves of the plant, DPPH• and ABTS•+ scavenging, Fe+3 reducing activity, α-amylase, and α-glucosidase inhibition assays were performed. The oleuropein content of the absolute ethanol extract with the highest activity was analysed by HPLC. The characterized extract was loaded into liposomes and chitosan coated liposomes, and the long-term sustainability of their activity was investigated. The encapsulation efficiency was 65.2% for the liposome and 66.8% for the chitosan-coated liposome formulation. The amounts of the extracts released from the formulations were evaluated to exhibit antioxidant and antidiabetic activity.

Biomonitoring of Oxidative-Stress-Related Genotoxic Damage in Patients with End-Stage Renal Disease.

Chronic kidney disease (CKD), a common progressive renal failure characterized by the permanent loss of functional nephrons can rapidly progress to end-stage renal disease, which is known to be an irreversible renal failure. In the therapy of ESRD, there are controversial suggestions about the use of regular dialysis, since it is claimed to increase oxidative stress, which may increase mortality in patients. In ESRD, oxidative-stress-related DNA damage is expected to occur, along with increased inflammation. Many factors, including heavy metals, have been suggested to exacerbate the damage in kidneys; therefore, it is important to reveal the relationship between these factors in ESRD patients. There are very few studies showing the role of oxidative-stress-related genotoxic events in the progression of ESRD patients. Within the scope of this study, genotoxic damage was evaluated using the comet assay and 8-OHdG measurement in patients with ESRD who were undergoing hemodialysis. The biochemical changes, the levels of heavy metals (aluminum, arsenic, cadmium, lead, and mercury) in the blood, and the oxidative biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were evaluated, and their relationship with genotoxic damages was revealed. Genotoxicity, oxidative stress, and heavy-metal levels, except mercury, increased significantly in all renal patients. DNA damage, 8OHdG, and MDA significantly increased, and GSH significantly decreased in patients undergoing dialysis, compared with those not having dialysis. The duration and the severity of disease was positively correlated with increased aluminum levels and moderate positively correlated with increased DNA damage and cadmium levels. In conclusion, this study revealed that the oxidative-stress-related DNA damage, and also the levels of Al and Cd, increased in ESRD patients. It is assumed that these changes may play an important role in the progression of renal damage. Approaches for reducing oxidative-stress-related DNA damage and heavy-metal load in ESRD patients are recommended.

Independent predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B

SUMMARY OBJECTIVE: There are limited data on non-alcoholic fatty liver disease in chronic hepatitis B virus infection. We aimed to determine the predictors for non-alcoholic fatty liver disease in patients with treatment-naïve chronic hepatitis B virus infection. METHODS: All consecutive treatment-naïve patients with chronic hepatitis B virus infection at the Haseki Training and Research Hospital between October 1, 2021, and September 31, 2022, were retrospectively enrolled. Chronic hepatitis B virus infection is defined by positive serum hepatitis B surface antigen for 6 months or more. Patients with significant alcohol consumption, prolonged steatogenic drug use, malignancy, monogenic hereditary disorders, patients co-infected with hepatitis D virus, hepatitis C virus infection, or human immunodeficiency virus were excluded. Demographic characteristics, anthropometric determinants, laboratory findings, and virological parameters were retrospectively collected from patients' charts and electronic medical records. RESULTS: A total of 457 patients with treatment-naïve chronic hepatitis B virus infection were included in the study. The three multivariate regression models revealed that age (p<0.028), body mass index (p=0.046), diabetes mellitus (p=0.030), hemoglobin (p=0.008), platelet (p=0.012), and triglyceride (p=0.002) in Model 1; body mass index (p=0.033), diabetes mellitus (p<0.001), hemoglobin (p=0.008), platelet (p=0.004), LDL (p=0.023), and HDL (p=0.020) in Model 2; and age (p<0.001), body mass index (p=0.033), hemoglobin (p=0.004), platelet (p=0.004), and HDL (p=0.007) in Model 3 were independent predictors. CONCLUSION: Non-alcoholic fatty liver disease was observed in about one-third of patients with chronic hepatitis B virus infection and was positively associated with older age, higher body mass index, presence of comorbid conditions including diabetes mellitus, increased levels of metabolic laboratory parameters, especially serum triglyceride and LDL, and decreased HDL.

Assessment of the biointeractivity of a novel vital pulp therapy agent derived from eggshell biowaste: An in vitro study.

This study aimed to assess the calcium (Ca2+ ) and hydroxyl (OH- ) ion-releasing ability, namely the biointeractivity of eggshell-derived hydroxyapatite (ESDHA) in comparison with mineral trioxide aggregate (MTA) and calcium hydroxide (CH). ESDHA, MTA and CH samples (n = 10; 8 × 1.6 mm) were immersed in 10 mL of deionised water (37°C, pH 6.8). Ca2+ and OH- ion releases were detected in 1, 7 and 21 days. Scanning electron microscopy and Fourier transform infrared spectroscopy analyses were also conducted. IBM SPSS 20.0 was used for statistical analyses. The cumulative Ca2+ ions (56.22 ± 11.28 ppm) were detected as most significant in ESDHA (day 21; p < 0.05). The OH- ion values of the ESDHA group were statistically higher than MTA and CH (days 1 and 7; p < 0.05). ESDHA and CH showed a similar pattern with sharp peaks in Ca2+ , oxygen and carbon elements. ESDHA being a sustainable material with a high ion-releasing ability may be a preferable alternative to the commercial vital pulp therapy agents.

Comparative Metabolomic Profiles of Vascular Involvement in Behçet's Disease.

BACKGROUND: Behçet's disease is a systemic, inflammatory disease affecting multiple organs. Vascular involvement is the main cause of morbidity and mortality in Behçet's disease patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidence in this patient group. The aim of this study is to investigate the unique metabolic signatures of Behçet's disease patients with vascular involvement. METHODS: Metabolomic profiling was performed on serum samples of 48 Behçet's disease patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometrybased untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. RESULTS: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of Behçet's disease, vascular involvement in Behçet's disease, and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis, could be an important stage for developing Behçet's disease. CONCLUSION: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of Behçet's disease pathogenesis and also developing vascular involvement in Behçet's disease at the metabolite level. The results showed that vascular involvement in Behçet's disease could be highly linked with amino acid metabolism and also the antioxidant system, and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of Behçet's disease and also for vascular involvement in Behçet's disease.

Thiol-Disulphide Homeostasis, Ischemia-Modified Albumin, Trace Elements and Vitamins in Vitiligo Patients.

Background: Vitiligo, a multifactorial, depigmented skin disease, is characterised by selective loss of functional melanocytes leading to pigment reduction in the affected areas of the skin. Aim: We aimed to examine thiol-disulphide homeostasis, IMA, copper, zinc, selenium, vitamin A and vitamin C levels in vitiligo patients. Materials and Methods: The study included 83 vitiligo patients and 72 healthy controls. Copper, zinc, and selenium levels were measured by atomic absorption spectrophotometer; vitamin A and E levels were measured by high-performance liquid chromatography. Ischemia-modified albumin and native/total thiol levels were measured by colourimetric method. Results: Serum native and total thiol levels were significantly lower in vitiligo patients (P < 0.001, for all). Zn levels were significantly higher in vitiligo patients than in the control group (P = 0.004). There was no statistical difference in terms of Cu, Se, vitamin A and vitamin E levels. Conclusions: All thiol-disulphide homeostasis parameters (the most important antioxidant-oxidant system in circulation), trace elements, and vitamins together were evaluated in the present study in vitiligo patients. It can be concluded that vitiligo patients have increased oxidative stress status, and also the increase in the dissemination of the disease also increases the oxidative stress in the body.

Blood pressure response to exercise in unaffected relatives of autosomal dominant polycystic kidney disease patients: an observational study.

INTRODUCTION: Hypertension is an early finding of autosomal dominant polycystic kidney disease (ADPKD) and is related to different mechanisms. Cyst expansion-related renin secretion or early endothelial dysfunctions are some of these hypotheses. In addition, the underlying genetic factor is thought to play a role in the inheritance of hypertension. The differential course of hypertension in ADPKD preoccupies that relatives of ADPKD patients may also be at risk for this underlying mechanisms with a genetically determined abnormal endothelial-vascular state. In this study, we aimed to evaluate blood pressure response to exercise as an initial vascular problem in unaffected and normotensive relatives of hypertensive ADPKD patients. METHODS: This is an observational study including unaffected and normotensive relatives (siblings and children) of ADPKD patients (relative group) and healthy controls (control group) who performed an exercise stress test. A 6-lead electrocardiogram was recorded and blood pressure was measured automatically with a cuff worn on the right arm, immediately before the test and every 3 min during the exercise and the recovery phase. Participants continued the test until their age-specific target heart rate was reached or symptoms occurred that required discontinuation of the test. The highest blood pressure and pulse values during exercise were noted. In addition, as a marker for endothelial function, nitric oxide (NO) and asymmetric dimethylarginine (ADMA) levels were measured at baseline and post-exercise. RESULTS: There were 24 participants in the relative group (16 female, mean age 38.45 years) and 30 participants in the control group (15 female, mean age 37.96 years). Two groups were similar in terms of age, gender, body mass index (BMI), smoking status, resting systolic blood pressure (SBP)/diastolic blood pressure (DBP) and biochemical parameters. Mean SBP and DBP were similar in both groups during 1st, 3rd and 9th minutes of exercise (1st minute: 136.25 ± 19.71 mmHg vs 140.36 ± 30.79 mmHg for SBP, p = 0.607, 84.05 ± 14.75 mmHg vs 82.60 ± 21.60 mmHg for DBP, p = 0.799; 3rd minute: 150.75 ± 30.39 mmHg vs 148.54 ± 27.30 mmHg for SBP, p = 0.801, 98.95 ± 26.92 mmHg vs 85.92 ± 17.93 mmHg for DBP, p = 0.062; 9th minute: 156.35 ± 30.84 mmHg vs 166.43 ± 31.90 mmHg for SBP, p = 0.300, 96.25 ± 21.99 mmHg vs 101.78 ± 33.11 mmHg for DBP, p = 0.529 for control and relatives, respectively). During the recovery phase, SBP decreased in both groups in 6th minute (119.85 ± 14.06 mmHg vs 122.86 ± 16.76 mmHg, p = 0.538 for control and relatives respectively); however, in the relatives of ADPKD patients DBP remained high at the end of the 6th minute (78.95 ± 11.29 mmHg vs 86.67 ± 9.81 mmHg p = 0.025 for control and relatives, respectively). Baseline and post-exercise NO and ADMA levels were similar in both groups (Baseline p = 0.214 and p = 0.818, post-exercise p = 0.652 and p = 0.918 for NO and ADMA, respectively). CONCLUSION: Abnormal blood pressure response to exercise was observed in unaffected normotensive relatives of ADPKD. Although its clinical significance needs to be demonstrated by additional research, it is an important finding that unaffected relatives of ADPKD may be at risk for an altered arterial vascular network. Furthermore, these data are the first to demonstrate that relatives of ADPKD patients may also be under risk with a genetically determined abnormal vascular state.

Evaluation of preoperative procollagen type 1 N-terminal peptide and collagen type 1 C-telopeptide levels in the prediction of postoperative hypocalcemia in patients undergoing parathyroidectomy due to primary hyperparathyroidism.

PURPOSE: This study is aimed at investigating the role of preoperative procollagen type 1 N-terminal peptide (P1NP) and collagen type 1 C-telopeptide (CTx) levels in predicting the development of postoperative hypocalcemia in primary hyperparathyroidism (PHPT). METHODS: In this prospective observational study, preoperative complaints of patients with primary hyperparathyroidism and their urea, creatinine, glomerular filtration rate (GFR), calcium, albumin, urinary calcium, parathyroid hormone, and bone mineral density (BMD) were recorded. P1NP and CTx levels were analyzed in blood samples taken the day before surgery, and their relationship with calcium levels obtained on the first postoperative day was examined. RESULTS: The median age was 53 years for patients who developed hypocalcemia and 62 years for those who did not develop hypocalcemia (p = 0.01). The urea, creatinine, and GFR values were determined as 22 mcg/dl, 0.61 mcg/dl, and 105 ml/min, respectively, for the hypocalcemia group (Group 1) and 30.5 mcg/dl, 0.74 mcg/dl, and 90 ml/min, respectively, for the non-hypocalcemia group (Group 2) (p = 0.02, 0.001, and 0.01, respectively). The BMD femur Z-score was - 0.1 in Group 1 and 0.8 in the Group 2 (p = 0.02). The mean CTx values were 4.14 pg/dl and 1.98 pg/dl (p = 0.036), and the mean P1NP values were 252.84 mcg/dl and 269.04 mcg/dl (p = 0.427) for Groups 1 and 2, respectively. According to multivariate analysis, only CTx was a significant independent predictor of hypocalcemia (odds ratio 1.739). CONCLUSION: CTx level is a significant factor in predicting the risk of developing early postoperative hypocalcemia in patients scheduled for surgery due to primary hyperparathyroidism.

Decreased serum levels of α-synuclein in patients with schizophrenia and their unaffected siblings.

AIM: The final common pathway in the etiopathogenesis of schizophrenia is suggested that there is a defect in the presynaptic terminal in dopaminergic transmission, in which α-synuclein has an important role. Peripheral biomarker studies in schizophrenia have become crucial for better diagnoses, early interventions, and personalized therapies. This study aims to compare α-synuclein levels in patients with schizophrenia and their unaffected siblings with healthy controls, as a potential peripheral biomarker for schizophrenia. METHODS: The quantifications of α-synuclein serum concentrations were conducted by the ELISA method. PANSS and CGI-S were used to analyse the severity of the symptoms of the subjects. Data were analysed by nonparametric tests and the Receiver Operating Curve (ROC) analysis. RESULTS: Sixty-two patients with schizophrenia (mean age: 34,8 ± 9,9, %64,5 male), their 56 unaffected siblings (mean age: 39,4 ± 11,5, %55,4 male) and 56 healthy controls (mean age: 36,2 ± 9,8, %64,3 male) were included. α-synuclein levels were significantly lower in the patient (27,65 (12,61-46,09) pg/ml) and the unaffected sibling groups (24,62 (15,60-57,87) pg/ml) compared with healthy controls (45,58 (11,25-108,30) pg/ml) (p < .001). According to the ROC analysis, the optimal cut-off value for α-synuclein levels in distinguishing the schizophrenia group from the control group was 42.20. The sensitivity of the measurement of serum α-synuclein at this point was 93.5%, and the specificity was 60.7%. CONCLUSION: Our study demonstrates that decreased levels of serum α-synuclein may be utilized as a possible peripheral biomarker of familial risk for schizophrenia in both patients and their siblings.

Melissa officinalis L. nanoethosomal formulation: evaluation of antioxidant, enzyme inhibitory activities and in vitro toxicity.

This work aimed to create an extract of Melissa officinalis L. with strong antiradical efficacy, characterize it, and enhance its long-term efficacy by developing an ethosomal formulation. DPPH and ABTS assays were used to test the antiradical activity of extracts with different ethanol ratios obtained from the aerial part. Phytochemical characterization of the extract with the highest activity, ethyl acetate fraction of 60% ethanol extract, was analyzed by HPLC. The active ethyl acetate fraction was loaded into ethosomes, and characterization and release studies of the formulation were performed. The released extract from the formulation exhibited substantial antiradical action as well as inhibition of collagenase (71.5%) and elastase (75.5%) enzymes. The toxicity of the active extract and the formulation was determined in the mouse fibroblast cell line. This study successfully developed a long-term antioxidant and enzyme inhibitor formulation containing M. officinalis, which stands out for its medicinal properties.

Assessment of Phenolic Composition, Antioxidant Potential, Antimicrobial Properties, and Antidiabetic Activity in Extracts Obtained from Schinus molle L. Leaves and Fruits.

BACKGROUND: The current research centers on exploring the antioxidant, antimicrobial, and antidiabetic features of Schinus molle L. grown in Turkey. METHODS: Quantitative analysis of chlorogenic acid, caffeic acid, and hyperoside levels in leaf, ripe fruit, and raw fruit extracts was conducted using High-Performance Liquid Chromatography (HPLC) in a 70% methanol-water mixture. Among the extracts, the methanol extract from ripe fruits displayed the highest chlorogenic acid concentration, measuring at 2.040% ± 0.172% standard deviation (SD). Moreover, analysis of their total phenolic and flavonoid contents was carried out. Antioxidant power was assessed through different chemical assays, together with their antimicrobial and anti-diabetic properties. RESULTS: The results of DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), and reducing power assays showed that leaf and ripe fruit alcoholic extract exhibited peak performance. While the MIC ( minimum inhibitory concentration) values of the extracts were determined to have moderate bactericidal effects on Staphylococcus aureus, Escherichia coli, and Candida albicans it was observed that none of the extracts displayed biofilm inhibition. The inhibition percentage of α-glucosidase enzyme activity for the methanol extract of raw fruits was determined to be 99.11 ± 1.61. In diabetic ß-TC cells, glucose level was measured as 129 ± 2.03 mg/dL, and insulin amount was measured as 37.2 ± 0.02 mg/dL. CONCLUSIONS: The findings of our study seem to have important implications for future research, as Schinus molle L. may be a potential pharmaceutical candidate with important pharmacological activities.

Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations.

Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, is one of the most popular spices worldwide, known since ancient times, and used both as a spice and a medicinal plant. The phenolic compounds found in ginger are predominantly gingerols, shogaols, and paradols. Gingerols are the major phenolic compounds found in fresh ginger and contain mainly 6-gingerol as well as 4-, 5-, 8-, 10-, and 12-gingerols. Gingerols possess a wide array of bioactivities, such as antioxidant and anticancer, among others. Regarding the different array of biological activities and published data on the mechanisms underlying its action, the complex interaction between three key events, including inflammation, oxidative stress, and immunity, appears to contribute to a plethora of pharmacological activities of this compound. Among these, the immunomodulatory properties of these compounds, which attract attention due to their effects on the immune system, have been the focus of many studies. Gingerols can alleviate inflammation given their ability to inhibit the activation of protein kinase B (Akt) and nuclear factor kappa B (NF-κB) signaling pathways, causing a decrease in proinflammatory and an increase in anti-inflammatory cytokines. However, given their low bioavailability, it is necessary to develop new and more effective strategies for treatment with gingerols. In order to overcome this problem, recent studies have addressed new drug delivery systems containing gingerols. In this review, the immunomodulatory activities of gingerol and its underlying mechanisms of action combined with the contributions of developed nanodrug delivery systems to this activity will be examined.

The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.

BACKGROUND: Increased bone turnover is a hallmark of hyperthyroidism. The underlying factors of how thyroid hormones affect bone cells are still under the spotlight. Previous studies indicated serum osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and interleukin-6 (IL-6) as mediators of the effect of thyroid hormones on bone metabolism. Ultimately, the present research aimed to examine the association of IL-6 with OPG and RANKL in patients with hyperthyroidism. METHODS: We carried out this study with 39 newly diagnosed and untreated Graves' patients and 43 healthy controls. In addition to routine tests, we measured serum OPG, RANKL, and IL-6 levels. RESULTS: Mean age and sex distribution were similar in both groups. The hyperthyroid group had significantly higher OPG (p = 0.002) and IL-6 (p < 0.001) levels, but RANKL levels were significantly lower in this group (p < 0.001). We found OPG not to correlate with free T4 and T3, while it had a moderate and negative correlation with thyrotropin (TSH) (r = -0.372, p = 0.001). IL-6 had no correlation with OPG but positively correlated with free T4 (r = 0.445, p < 0.001) and free T3 (r = 0.326, p = 0.035). It also negatively correlated with RANKL (r = -0.247, p = 0.033). DISCUSSION: Maintaining skeletal development and integrity is partially regulated by a normal balance of thyroid hormones. We concluded that increases in serum OPG and IL-6 levels accompanied hyperthyroidism. However, excessive levels of the hormones might cause drops in serum RANKL levels. Our results suggested that OPG, RANKL, and IL-6 might be involved in the cross-talking among immunity, thyroid function, and bone metabolism in the case of hyperthyroidism.

Serum concentrations of aminoacylase 1 in schizophrenia as a potential biomarker: a case-sibling-control study.

PURPOSE: Aminoacylase 1 (ACY1) catalyzes the hydrolysis reaction during protein degradation. N-acetylamino acids are accumulated in the urine in Aminoacylase 1 deficiency (ACY1D). This study attempts to evaluate the potential of ACY1 as a biomarker for schizophrenia and predict genetic vulnerability in the high-risk population. MATERIAL AND METHODS: Seventy patients with schizophrenia, twenty-five of which have newly diagnosed, forty-nine unaffected siblings of patients, and fifty-six healthy controls were included in the study. The ELISA method was used to measure serum ACY1. The Positive and Negative Syndrome Scale (PANSS) and The Clinical Global Impression - Severity scale (CGI-S) were used to analyze the severity of the symptoms. Data were analysed statistically by non-parametric tests. RESULTS: The finding of the study indicated that the serum levels of ACY1 in patients and siblings were lower compared to healthy controls (p < 0.001 and p = 0.023). There was no statistically significant difference between patients and siblings (p = 0.067). The duration of disease, PANSS total scores, and CGI-S scores did not have a significant association with the ACY1 levels in the patient group (p > 0.005). ACY1 levels among the drug-using patient group and the newly diagnosed patient group showed no notable difference (respectively, p = 0.120 and p = 0.843). CONCLUSION: This study is the first to evaluate the serum ACY1 levels in patients with schizophrenia. The result of the study provides us insight regarding the first hints that ACY1 might be a potential biomarker. Being aware of the molecule will pave the way for further explorations in the field.

Ethosomal (-)-epigallocatechin-3-gallate as a novel approach to enhance antioxidant, anti-collagenase and anti-elastase effects.

Controlled release systems containing natural compounds have been successfully applied in cosmetics as antiaging products to enhance the penetration of active compounds through the skin. In this study, we aimed to develop novel ethosomal formulations containing a potent antioxidant, epigallocatechin-3-gallate (EGCG), and to evaluate their potential for use in cosmetics by determining their antioxidant and antiaging effects. Ethosomes (ETHs) were prepared via mechanical dispersion and characterized in vitro in terms of particle size (PS), zeta potential (ZP), polydispersity index (PDI), encapsulation efficiency percentage (EE%), and in vitro release. The best ETH formulation was used to prepare the ethosome-based gel (ETHG) by using Carbopol 980 as a gelling agent at a ratio of 1:1 (v/v). The gel formulation was evaluated regarding organoleptic properties, pH values, and viscosity. Stability studies were conducted for three months and changes in characterization parameters and residual EGCG content of ETHs were examined. Besides, for ETHG, organoleptic properties, pH values (every two weeks), and viscosity (first and twelfth week) were determined for three months. The 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the cytotoxicity of the formulations and different EGCG solutions on the L929 cell line. The cell permeation properties and inhibitory effects of ETHs and ETHGs on collagenase and elastase enzymes were investigated compared to those of the solution form. Within the scope of antioxidant activity studies, 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•) radical scavenging and ß-carotene/linoleic acid co-oxidation inhibitory effects were carried out. The optimized EGCG-loaded ETHs (F3) were within the nanoscale range (238 ± 1.10 nm). The highest encapsulation efficiency and in vitro release values were 51.7 ± 1.15% and 50.8 ± 1.70%, respectively. The ETHG was successfully formulated with F3-coded ETHs and the cytotoxicity test revealed that the formulations and the EGCG solution at different concentrations were nontoxic. In terms of cell permeability, enzyme inhibition, and antioxidant activity, the ethosomal formulations yielded better results compared to the EGCG solution. It was observed that the formulations had a long-term effect due to the stability of EGCG. The findings of the study underline the potential of antioxidant and antiaging effects of the developed ethosomal formulations for use in the cosmetic field.

Investigation of thiol-disulfide homeostasis and ischemia-modified albumin levels in patients with hidradenitis supurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. The pathogenesis of HS is not clear, and the triggering mechanism for the initiation of the disease is still a controversy. AIMS: The present study aims to investigate the relationship between thiol-disulfide homeostasis (TDH), ischemia-modified albumin (IMA), and HS. To our knowledge, this will be the first report evaluating TDH and IMA status in HS. PATIENTS/METHODS: The study included 30 patients with HS as the patient group and 30 healthy individuals as the control group. For determination of HS severity, Hurley and Hidradenitis suppurativa physician global assessment (PGA) scores were used. One tube venous blood specimen from every participant was obtained. IMA and TDH tests were analyzed in sera of participants. The results were evaluated statistically. RESULTS: Disulfide (p < 0.001), Index I (p = 0.001), and Index II (p = 0.001) levels in HS group were significantly higher than control group. IMA levels in patients with higher Hurley scores are significantly higher (p = 0.032, r = 0.39). A positive correlation was observed between IMA level and disease duration (p = 0.021, r = 0.42). CONCLUSIONS: The shift in thiol/disulfide balance toward disulfide and significant increase in IMA levels put out the importance of oxidation status in HS etiopathogenesis.

Nanoemulsions Containing Megestrol Acetate: Development, Characterization, and Stability Evaluation.

Many active pharmaceutical ingredients (API) are poorly soluble in water and their low oral bioavailability is a major hindrance to their potential use. Megestrol acetate (MGA) is insoluble in water and its oral absorption is limited and considerably affected by food. Nanoemulsions (NEs) can be used as effective oral drug delivery systems where the hydrophobic API is loaded into the oil phase. In this study, MGA-loaded NEs were prepared based on the spontaneous emulsification technique. The effects of different excipients such as ethanol, Tween 80, Lipoid E80, and medium-chain triglyceride (MCT) on the NEs characterization were investigated. The experimental results indicated that optimum MGA-loaded NEs (F20) were nanometer-sized droplets (166.9 ± 3.0 nm) with negative zeta potential (-12.2 ± 1.1 mV). The effect of polyvinylpyrrolidone (PVP) on characteristic properties of F20 was also evaluated. On the selected NEs, in vitro dissolution tests and stability studies in various mediums and storage conditions were performed. The encapsulation efficiency of NEs were > 99%. The overall droplet size of F20 and PVP-2 (PVP-coated NEs) remained relatively stable as the pH changed from 1.2 to 6.8. It was determined that F20 and PVP-2 remained stable at 4°C until 12 weeks and had higher cytotoxicity on MCF-7 cells. To conclude, droplet size, surface charge, and stability are important properties for NEs to have sufficient effectiveness. In this study, alternative oral NEs of low-solubility drug MGA were developed considering the above features.