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.

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.

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.

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.

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.

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.

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.

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.

Evaluation of erythrocyte membrane fatty-acid compositions in association with interleukin-6 levels in patients with COVID-19.

OBJECTIVE: The cytokine storm presented in the hyperimmune response is related to poor prognosis in people with COVID-19. Interleukin-6 (IL-6) is one of the most prominent cytokines, especially on mucosal surfaces during infection, causing the cytokine storm. Polyunsaturated fatty acids (PUFAs) are the precursors of eicosanoids, which play critical roles in immune regulation and inflammation. The balance between ω-3 and ω-6 levels in the cell membrane has a critical role in regulating the equilibrium between proinflammatory and antiinflammatory processes and inducing IL-6 production. The present study focused on inflammatory and antiinflammatory mechanisms in COVID-19 over PUFAs and on relating their levels with disease prognosis and severity. METHODS: A total of 106 participants were included in the study. They were divided into three groups according to IL-6 level- 1: <35 pg/mL, 2: between 35 and 300 pg/mL, and 3: >300 pg/mL. Erythrocyte membrane PUFA compositions were analyzed by group. RESULTS: Levels of γ-linolenic acid and ω-6/ω-3 ratios were significantly increased in all comparison groups (P < 0.05). Total ω-6 and the ratio of arachidonic acid to eicosopentaenoic acid showed a statistically significant difference only between groups 1 and 3 (P < 0.05). There was a moderately negative correlation between total ω-3 and IL-6 and procalcitonin. There were positive correlations with ω-6/ω-3 ratio inflammatory markers, and the total ω-6 index also showed a moderately positive correlation with IL-6, procalcitonin, and D-dimer levels. CONCLUSIONS: The ratio of arachidonic acid to eicosopentaenoic acid, and ω-3 PUFAs, can be systemic signs of poor prognosis, increased lung damage, and high mortality in COVID-19, together with IL-6.

A New Perspective on the Treatment of Alzheimer's Disease and Sleep Deprivation-Related Consequences: Can Curcumin Help?

Sleep disturbances, as well as sleep-wake rhythm disorders, are characteristic symptoms of Alzheimer's disease (AD) that may head the other clinical signs of this neurodegenerative disease. Age-related structural and physiological changes in the brain lead to changes in sleep patterns. Conditions such as AD affect the cerebral cortex, basal forebrain, locus coeruleus, and the hypothalamus, thus changing the sleep-wake cycle. Sleep disorders likewise adversely affect the course of the disease. Since the sleep quality is important for the proper functioning of the memory, impaired sleep is associated with problems in the related areas of the brain that play a key role in learning and memory functions. In addition to synthetic drugs, utilization of medicinal plants has become popular in the treatment of neurological diseases. Curcuminoids, which are in a diarylheptanoid structure, are the main components of turmeric. Amongst them, curcumin has multiple applications in treatment regimens of various diseases such as cardiovascular diseases, obesity, cancer, inflammatory diseases, and aging. Besides, curcumin has been reported to be effective in different types of neurodegenerative diseases. Scientific studies exclusively showed that curcumin leads significant improvements in the pathological process of AD. Yet, its low solubility hence low bioavailability is the main therapeutic limitation of curcumin. Although previous studies have focused different types of advanced nanoformulations of curcumin, new approaches are needed to solve the solubility problem. This review summarizes the available scientific data, as reported by the most recent studies describing the utilization of curcumin in the treatment of AD and sleep deprivation-related consequences.

Advances in Understanding the Role of Aloe Emodin and Targeted Drug Delivery Systems in Cancer.

Cancer is one of the important causes of death worldwide. Despite remarkable improvements in cancer research in the past few decades, several cancer patients still cannot be cured owing to the development of drug resistance. Natural sources might have prominence as potential drug candidates. Among the several chemical classes of natural products, anthraquinones are characterized by their large structural variety, noticeable biological activity, and low toxicity. Aloe emodin, an anthraquinone derivative, is a natural compound found in the roots and rhizomes of many plants. This compound has proven its antineoplastic, anti-inflammatory, antiangiogenic, and antiproliferative potential as well as ability to prevent cancer metastasis and potential in reversing multidrug resistance of cancer cells. The anticancer property of aloe emodin, a broad-spectrum inhibitory agent of cancer cells, has been detailed in many biological pathways. In cancer cells, these molecular mechanisms consist of inhibition of cell growth and proliferation, cell cycle arrest deterioration, initiation of apoptosis, antimetastasis, and antiangiogenic effect. In accordance with the strategy of developing potential drug candidates from natural products, aloe emodin's low bioavailability has been tried to be overcome by structural modifications and nanocarrier systems. Consequently, this review summarizes the antiproliferative and anticarcinogenic properties of aloe emodin, as well as the enhanced activity of its derivatives and the advantages of drug delivery systems on bioavailability.

Evaluation of the relationship of lymphangiogenesis markers with disease pathogenesis in patients with Behçet's uveitis.

OBJECTIVES: The present study aims to evaluate the relationship between Behçet's uveitis and lymphangiogenesis by determining levels of Vascular endothelial growth factor-C (VEGF-C, its receptors sVEGFR-2, sVEGFR-3 and lymphangiogenesis markers podoplanin (PDPN) and lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1), and C-type lectin domain family 1 member B (CLEC2). MATERIALS AND METHODS: 55 patients with BD uveitis and 31 healthy control subjects were enrolled in the study. RESULTS: sVEGFR-2, sVEGFR-3, VEGF-C/sVEGFR-2 ratio, PDPN and LYVE-1 levels were higher in the patient group. A positive correlation was found between LYVE-1 and hsCRP levels. PDPN had a strong predictive value for progression with a cut-off value of 2 pg/mL, with 69% sensitivity and 68% specificity (p = 0.001). CONCLUSION: LYVE-1 and PDPN can be good representatives of the ongoing inflammatory processes in BD uveitis and point out that the disease can be related to lymphangiogenesis.

Serum IL-17 levels in patients with rosacea.

BACKGROUND: Rosacea is a chronic inflammatory skin disease characterized with increased serum and tissue inflammatory mediators. IL-17 is a well-known inflammatory mediator that plays important roles in pathogenesis of inflammatory skin diseases. Previous studies reported that Th17 pathway is activated in rosacea and IL-17, one of Th17 signature cytokines, is elevated in tissue samples of rosacea patients. OBJECTIVES: The aim of this study was to investigate serum IL-17 levels in rosacea patients and to study its relationship with disease characteristics. METHODS: Sixty patients diagnosed with rosacea and 60 healthy controls were included in the study. Serum IL-17 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The mean serum IL-17 level was 8.03 pg/mL (SD = 1.47) in rosacea patients and 7.37 pg/mL (Sd = 1.19) in controls. Serum IL-17 levels were significantly higher in rosacea (p = 0.002). Serum IL-17 levels were similar among patients with erythematotelangiectatic (ET) and papulopustular (PP) rosacea (8.02 vs 8.06, p = 0.83). Serum IL-17 levels did not correlate with rosacea severity (p = 0.59, r = 0.07 in ET rosacea; p = 0.88, r = 0.02 in PP rosacea), age of onset (p = 0.58, r = -0.07), and disease duration (p = 0.37, r = -0.11). Primary features and global assessments did not correlate with serum IL-17 levels (all p > 0.05). Among secondary features, edema showed a significant negative correlation with serum IL-17 concentrations (p = 0.037, r = -0.26). CONCLUSIONS: Our study showed increased serum IL-17 levels in rosacea patients and a significant correlation between IL-17 concentrations and secondary features of the disease suggesting IL-17 may contribute to pathogenesis of rosacea and may be a new target for rosacea treatment.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet's uveitis.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. OBJECTIVES: To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). MATERIAL AND METHODS: Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. CONCLUSIONS: The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin.

Many anticancer active compounds are known to have the capacity to destroy pathologically proliferating cancer cells in the body, as well as to destroy rapidly proliferating normal cells. Despite remarkable advances in cancer research over the past few decades, the inclusion of natural compounds in researches as potential drug candidates is becoming increasingly important. However, the perception that the natural is reliable is an issue that needs to be clarified. Among the various chemical classes of natural products, anthraquinones have many biological activities and have also been proven to exhibit a unique anticancer activity. Emodin, an anthraquinone derivative, is a natural compound found in the roots and rhizomes of many plants. The anticancer property of emodin, a broad-spectrum inhibitory agent of cancer cells, has been detailed in many biological pathways. In cancer cells, these molecular mechanisms consist of suppressing cell growth and proliferation through the attenuation of oncogenic growth signaling, such as protein kinase B (AKT), mitogen-activated protein kinase (MAPK), HER-2 tyrosine kinase, Wnt/-catenin, and phosphatidylinositol 3-kinase (PI3K). However, it is known that emodin, which shows toxicity to cancer cells, may cause kidney toxicity, hepatotoxicity, and reproductive toxicity especially at high doses and long-term use. At the same time, studies of emodin, which has poor oral bioavailability, to transform this disadvantage into an advantage with nano-carrier systems reveal that natural compounds are not always directly usable compounds. Consequently, this review aimed to shed light on the anti-proliferative and anti-carcinogenic properties of emodin, as well as its potential toxicities and the advantages of drug delivery systems on bioavailability.

Serum galectin-3 levels in patients with psoriasis.

INTRODUCTION: Galectin-3 is a ß-galactoside-binding lectin associated with cellular proliferation, inflammation and angiogenesis, which are the major characteristics of psoriatic skin. OBJECTIVES: To investigate serum galectin-3 levels in psoriasis patients compared with healthy controls and to study its relationship with disease characteristics. METHODS: Seventy-eight patients diagnosed with psoriasis and 78 age- and sex-matched healthy volunteers were included in the study. Serum galectin-3, IL-17, IL-6 and TNF-α levels were measured using Enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum Galectin-3, IL-17, IL-6 and TNF-α levels were significantly higher in psoriasis patients compared with control group (P < .001, P = .003, P < .001 and P < .001, respectively). A cut-off value of 10 ng/mL for galectin-3 was set after receiver operating characteristic analysis. A serum galectin-3 level >10 ng/mL increased the risk of psoriasis by 14.5 times (95% CI: 6.6-32.3, P < .001) and a serum galectin-3 level >10 ng/mL predicted psoriasis with 83.3% sensitivity and 74.3% specificity. No statistically significant association was observed between serum galectin-3 concentrations and disease characteristics including disease severity, presence of psoriatic arthritis, nail involvement and psoriatic comorbidity. No statistically significant correlation was observed between serum galectin-3 level and serum IL-17, IL-6 and TNF-α levels (all three P values > .05). CONCLUSIONS: Elevated serum galectin-3 levels in psoriasis patients may indicate a possible role of galectin-3 in pathogenesis of psoriasis.

Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

AIM: Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. METHOD: Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. RESULTS: Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P < .001). CONCLUSION: This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

Oxidative Stress and Marine Carotenoids: Application by Using Nanoformulations.

Carotenoids are natural fat-soluble pigments synthesized by plants, algae, fungi and microorganisms. They are responsible for the coloration of different photosynthetic organisms. Although they play a role in photosynthesis, they are also present in non-photosynthetic plant tissues, fungi, and bacteria. These metabolites have mainly been used in food, cosmetics, and the pharmaceutical industry. In addition to their utilization as pigmentation, they have significant therapeutically applications, such as improving immune system and preventing neurodegenerative diseases. Primarily, they have attracted attention due to their antioxidant activity. Several statistical investigations indicated an association between the use of carotenoids in diets and a decreased incidence of cancer types, suggesting the antioxidant properties of these compounds as an important factor in the scope of the studies against oxidative stress. Unusual marine environments are associated with a great chemical diversity, resulting in novel bioactive molecules. Thus, marine organisms may represent an important source of novel biologically active substances for the development of therapeutics. Marine carotenoids (astaxanthin, fucoxanthin, ß-carotene, lutein but also the rare siphonaxanthin, sioxanthin, and myxol) have recently shown antioxidant properties in reducing oxidative stress markers. Numerous of bioactive compounds such as marine carotenoids have low stability, are poorly absorbed, and own very limited bioavailability. The new technique is nanoencapsulation, which can be used to preserve marine carotenoids and their original properties during processing, storage, improve their physiochemical properties and increase their health-promoting effects. This review aims to describe the role of marine carotenoids, their potential applications and different types of advanced nanoformulations preventing and treating oxidative stress related disorders.

Combretastatins: An Overview of Structure, Probable Mechanisms of Action and Potential Applications.

Combretastatins are a class of closely related stilbenes (combretastatins A), dihydrostilbenes (combretastatins B), phenanthrenes (combretastatins C) and macrocyclic lactones (combretastatins D) found in the bark of Combretum caffrum (Eckl. & Zeyh.) Kuntze, commonly known as the South African bush willow. Some of the compounds in this series have been shown to be among the most potent antitubulin agents known. Due to their structural simplicity many analogs have also been synthesized. Combretastatin A4 phosphate is the most frequently tested compounds in preclinical and clinical trials. It is a water-soluble prodrug that the body can rapidly metabolize to combretastatin A4, which exhibits anti-tumor properties. In addition, in vitro and in vivo studies on combretastatins have determined that these compounds also have antioxidant, anti-inflammatory and antimicrobial effects. Nano-based formulations of natural or synthetic active agents such as combretastatin A4 phosphate exhibit several clear advantages, including improved low water solubility, prolonged circulation, drug targeting properties, enhanced efficiency, as well as fewer side effects. In this review, a synopsis of the recent literature exploring the combretastatins, their potential effects and nanoformulations as lead compounds in clinical applications is provided.