ORCID Profile
0000-0002-7446-3927
Current Organisation
Deakin University
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.TEM.2018.10.004
Abstract: Cancer is the second leading cause of death in western countries, and thus represents a major global public health issue. Whilst it is well-recognized that diet, obesity, and smoking are risk factors for cancer, the role of low levels of high-density lipoprotein cholesterol (HDL-C) in cancer is less well appreciated. Conflicting evidence suggests that serum HDL-C levels may be either positively or negatively associated with cancer incidence and mortality. Such disparate associations are supported in part by the multitude of high-density lipoprotein (HDL) functions that can all have an impact on cancer cell biology. The aim of this review is to provide a comprehensive overview of the crosstalk between HDLs and cancer, focusing on the molecular mechanisms underlying this association.
Publisher: Springer Science and Business Media LLC
Date: 17-03-2015
DOI: 10.1007/S11655-015-2160-Z
Abstract: To investigate the effectiveness of curcumin, a natural polyphenolic compound with antioxidant and anti-inflammatory activities, on the frequency of symptoms of anxiety and depression in obese in iduals. In this double blind, cross-over trial, 30 obese subjects were randomized to receive either curcumin (1 g/day) or placebo for a period of 30 days. Following a wash-out interval of 2 weeks, each subject was crossed over to the alternative regimen for a further 30 days. Severity of anxiety and depression was assessed at baseline and at weeks 4, 6 and 10 of the trial using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales, respectively. Mean BAI score was found to be significantly reduced following curcumin therapy (P=0.03). However, curcumin supplementation did not exert any significant impact on BDI scores (P=0.7). Curcumin has a potential anti-anxiety effect in in iduals with obesity.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.PHRS.2017.02.008
Abstract: Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.
Publisher: Wiley
Date: 10-07-2019
DOI: 10.1002/IUB.2105
Abstract: High-density lipoproteins (HDLs) are the smallest lipoprotein with the highest level of protein in their surface. The main role of HDLs are reverse transport of cholesterol from peripheral tissues to the liver. More recently, HDLs have been considered as a new drug delivery system because of their small size, proper surface properties, long circulation time, biocompatibility, biodegradability, and low immune stimulation. Delivery of anticancer drug to the tumor tissue is a major obstacle against successful chemotherapy, which is because of the toxicity and poor aqueous solubility of these drugs. Loading chemotherapeutic drugs in the lipid core of HDLs can overcome the aforementioned problems and increase the efficiency of drug delivery. In this review, we discuss the use of HDLs particles in drug delivery to the tumor tissue and explain some barriers and limitations that exist in the use of HDLs as an ideal delivery vehicle.
Publisher: Springer International Publishing
Date: 2021
Publisher: Termedia Sp. z.o.o.
Date: 09-07-2022
DOI: 10.5114/AOMS/152000
Abstract: We aimed aimed to assess the effect of the immunotherapy with the PCSK9 peptide vaccine on the hepatic expression levels of microRNAs associated with LDLR pathway including miRNA-27a, miRNA-30c, and miRNA-191 in normal vaccinated mice. PCSK9 immunogenic peptide and 0.4% alum adjuvant were mixed at a 1:1 ratio and used as a vaccine formulation. Male albino mice were randomly assigned into vaccine or control groups. Mice in the vaccine group were injected four times at two-week intervals with a PCSK9 peptide vaccine, and mice in the control group were injected with phosphate-buffered saline. Animal livers were s led two weeks after the last injection to assess miRNAs expression levels. The hepatic expression level of miRNA-27a, miRNA-30c, and miRNA-191 were evaluated by SYBR Green Real-Time PCR, quantified by comparative (2-ΔΔCT) method (Fold change) and normalized to U6 small nuclear RNA expression as an internal control. The hepatic expression level of miRNA-27a showed significant reduction in mice following immunotherapy with the PCSK9 peptide vaccine when compared to the control group (FC:0.731±0.1, P=0.027). Also, there was a borderline significant reduction in the hepatic expression level of miRNA-30c in the vaccinated group compared to the control (FC: 0.569±0.1, P=0.078). However, no significant differences were found in the hepatic expression level of miRNA-191 between two studied groups (FC: 0.852±0.1, P=0.343). According to the findings, the PCSK9 peptide vaccine could effectively reduce the hepatic expression level of miRNA-27a and may be helpful in the management of LDL-C level and atherosclerosis, which may be mediated through LDLR pathway.
Publisher: MDPI AG
Date: 06-02-2022
DOI: 10.3390/JCM11030849
Abstract: Objective: In-stent restenosis (ISR) is an unfavorable complication that occurs in patients after coronary stenting. Despite the progress with advent of modern DES and new antiplatelet agents, restenosis still h ers PCI short- and long-term results. The aim of this study was to investigate whether circulating miRNA-223, which is associated with HDL particles and involved in cholesterol efflux pathway, have diagnostic capability for determining ISR. Methods: This case–control study comprised 21 ISR and 26 NISR patients. The level of miRNA-223 expression was evaluated by TaqMan Real-Time PCR, quantified by the comparative method (fold change) and normalized to U6 expression. Results: Patients in ISR and NISR groups were not different in terms of demographic, clinical, and biochemical parameters, except that the percentage of patients who had DES was significantly greater in the NISR group (88.9%) in comparison with the ISR group (50%). The serum expression of miRNA-223 in ISR patients was 3.277 ± 0.9 times greater than that in NISR group (p = 0.016). In addition, the results of binary logistic regression demonstrated that the high level of serum miRNA-223 was strongly and positively associated with the ISR risk (OR: 17.818, 95% CI: 1.115–284.623, p = 0.042) after adjustment for age, sex, HDL-C, LDL-C, FBS, and statin consumption. Conclusion: Elevated serum level of miRNA-223 might be helpful in predicting the occurrence of ISR. Further confirmation in future large-scale studies is warranted.
Publisher: Wiley
Date: 28-10-2018
DOI: 10.1002/JCP.27362
Abstract: Poor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti‐inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.
Publisher: MDPI AG
Date: 14-12-2021
DOI: 10.3390/JCM10245867
Abstract: Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p 0.001), MPO activity (p 0.001), thiol (p 0.001), NO (p 0.01), and PAB (p 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p 0.001) and PAB (p 0.001) when compared to healthy subjects. Elevated levels of MDA (p 0.001) and PAB (p 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979 p = 0.033), and MDA (OR: 0.996 p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy in iduals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.
Publisher: Springer International Publishing
Date: 2021
DOI: 10.1007/978-3-030-73234-9_32
Abstract: Oxidative stress that occurs as a consequence of the imbalance between antioxidant activity and free radicals can contribute in the pathogenesis of metabolic disorders, such as type 2 diabetes mellitus (T2DM). Antioxidant therapies have been proposed as possible approaches to treat and attenuate diabetic complications. The purpose of this study was to evaluate potential antioxidant effects of trehalose on oxidative indices in a streptozotocin (STZ)-induced diabetic rat model. Diabetic rats were ided randomly into five treatment groups (six rats per group). One test group received 45 mg/kg/day trehalose via intraperitoneal injection, and another received 1.5 mg/kg/day trehalose via oral gavage for 4 weeks. Three control groups were also tested including nondiabetic rats as a normal control (NC), a nontreated diabetic control (DC), and a positive control given 200 mg/kg/day metformin. Levels of thiol groups (-SH), and serum total antioxidant capacity were measured between control and test groups. In addition, superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assessed. In both oral and injection trehalose-treated groups, a marked increase was observed in serum total antioxidant capacity (TAC) (p > 0.05) and thiol groups (-SH) (p < 0.05). Also, SOD and GPx activities were increased after 4 weeks of treatment with trehalose. In conclusion, the present results indicate ameliorative effects of trehalose on oxidative stress, with increase antioxidant enzyme activities in STZ-induced diabetic rats.
Publisher: Wiley
Date: 04-08-2018
DOI: 10.1002/JCP.27028
Abstract: Inflammation and lipid accumulation are two basic hallmarks of atherosclerosis as a chronic disease. Inflammation not only is a local response but can also be considered as a systemic process followed by an elevation of inflammatory mediators. Monocytes are a major source of proinflammatory species during atherogenesis. In atherosclerosis, modified low‐density lipoproteins (LDLs) are removed by macrophages these are recruited in the vessel wall, inducing the release of inflammatory cytokines in inflamed tissue. Hence, inflammatory cholesterol ester‐loaded plaque is generated. High‐density lipoprotein‐cholesterol (HDL‐C) exhibits antiatherosclerotic effects by neutralizing the proinflammatory and pro‐oxidant effects of monocytes via inhibiting the migration of macrophages and LDL oxidation in addition to the efflux of cholesterol from these cells. Furthermore, HDL plays a role in suppressing the activation of monocytes and proliferation–differentiation of monocyte progenitor cells. Thus, accumulation of monocytes and reduction of HDL‐C may participate in atherosclerosis and cardiovascular diseases (CVD). Given that the relationship between the high number of monocytes and low HDL‐C levels has been reported in inflammatory disorders, this review focused on understanding whether the monocyte‐to‐HDL ratio could be a convenient marker to predict atherosclerosis development and progression, hallmarks of CV events, instead of the in idual monocyte count or HDL‐C level.
Publisher: Elsevier BV
Date: 08-2021
DOI: 10.1016/J.SEMCANCER.2020.10.007
Abstract: An inverse correlation between high-density lipoprotein cholesterol (HDL-C) and cancer risk has been shown by several epidemiological studies. Some studies have even suggested that HDL-C can be used as a prognostic marker in patients with certain types of cancer. However, whether reduced HDL-C level is a consequential or causal factor in the development and progression of cancer remains a controversial issue. In this review, we update and summarize recent advances that highlight the role of HDL and some of its components in prognosis, diagnosis and treatment of cancer.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.BIOPHA.2022.112632
Abstract: In recent years, several trials investigated the role of anti-inflammatory agents in reducing cardiovascular events. Trehalose is a natural disaccharide able to reduce inflammation by enhancing macrophage autophagic activity. This action has been demonstrated to attenuate atherosclerotic plaque development in various pro-atherogenic animal models. However, at present, no data about the efficacy of this compound in human subjects have been published. We performed a randomized, double-blind trial involving 15 patients with history of myocardial infarction and evidence of systemic inflammation (defined as C-reactive protein > 2 mg/L). The patients were randomly assigned, in 2:1 ratio, to receive either intravenous trehalose (15 g once weekly) or placebo for 12 weeks. The primary efficacy end-point was the change in arterial wall inflammation, assessed by quantifying The MDS TBR change of the index vessel at 3-month follow-up was not significant in treatment and placebo groups. Furthermore, we could not demonstrate any significant difference between the trehalose group and control group in changes of cIMT from baseline to 3 months in the overall population. No significant changes in echocardiographic measurement were noted after trehalose treatment. Except for the change in urea level in placebo group (31.00 ± 6.59 vs. 25.60 ± 6.402 P = 0.038) no other changes were detected after treatment. Also, there was a significant difference between changes in alanine aminotransferase (ALT) trehalose and placebo groups. This was the first study that specifically assessed the effects of intravenous trehalose on atherogenesis in human subjects. Trehalose treatment was characterized by an optimal safety profile, but no significant reduction in arterial wall inflammation could be observed. This might be a consequence of the small s le size of this trial. Larger studies are needed to better assess the efficacy of this compound in this clinical context.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.PLIPRES.2017.05.001
Abstract: Although a selective strong elevation in the plasma level of low-density lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia (FH), also other plasma lipoprotein and lipid subspecies are changed in these patients. Several studies in FH patients have pointed to the qualitative abnormalities of high-density lipoprotein (HDL) particles, including their triglyceride and sphingomyelin enrichment, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant activities, and reduced plasma levels of miRs regulating HDL-dependent cholesterol efflux from macrophage foam cells, typical of atherosclerotic lesions. Thus, accurate understanding of HDL functionality and its disturbances in FH may serve a better estimation of the prognosis and also provide additional clues when searching for novel therapeutic choices in this disease. In spite of such a potential promise, there has been no prior comprehensive review focusing on indices of HDL function in FH patients. In the present review, we aim to fulfill this gap by identifying measures of HDL function that are impaired in FH, and by providing a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH.
Publisher: Termedia Sp. z.o.o.
Date: 29-07-2023
DOI: 10.5114/AOMS/170159
Abstract: This study aimed to evaluate the TRE-induced changes in the serum expression levels of miRNAs associated with lipids metabolism and autophagy process in MI patients to assess the potential protective effects of TRE in these patients. This post hoc investigation was performed on serum s les obtained from a pilot randomized, double blind, placebo-controlled clinical trial that recruited 14 men (aged 18-80) who had MI and systemic inflammation. The patients were randomized in a 2:1 ratio to either TRE (15 g/week, intravenous (IV) ad-ministration) (N=10) or placebo groups (equal volume of saline 0.9 %) (N=4) for a period of 12 weeks. To measure the relative serum expression levels of miRNA-155, miRNA-221, and miRNA-33, the SYBR Green qPCR method was used. miRNA-155 showed significantly higher serum expression levels in the TRE group (2.772±0.73 P=0.009) when compared to the placebo group. Also, significant reductions in miRNA-155 (0.171±0.03 P=0.016), miRNA-221 (0.116±0.07 P=0.013), and miRNA-33a (0.076±0.07 P=0.025) were observed in the placebo group at the end of the study. Nevertheless, the reduction (normalized to the baseline) of the serum expres-sion levels of miRNA-221 (FC:0.87±0.20 vs FC:0.18±0.08 P=0.009) and miRNA-33a (FC:0.73±0.22 vs FC:0.13±0.08 P=0.025) were significantly less in TRE group than in the placebo group. IV TRE administration did not reduce the expression of miRNA-221 and miRNA33a as much as placebo. Keeping a steady state of the serum expression levels of these miRNAs associated with lipoproteins metabolism and autophagy in the TRE group might have protective effects in patients with MI.
Publisher: Bentham Science Publishers Ltd.
Date: 17-09-2021
DOI: 10.2174/0929867328666210208182326
Abstract: The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.ATHEROSCLEROSIS.2017.10.018
Abstract: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by absence of insulin secretion due to destruction of the pancreatic beta-cells. Patients with T1D exhibit an increased risk for cardiovascular disease (CVD) compared with non-diabetic subjects. It has been established that low concentration of high-density lipoprotein cholesterol (HDL-C), an independent risk marker of CVD, coincides with a reduced protective capacity against oxidative stress. However, conflicting results have been reported on the prevalence of low HDL-C levels in T1D. Interestingly, changes in composition and function of HDL particles (abnormal ratio of cholesteryl ester-to-triglyceride, reduction in the phospholipid content, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant activities) have been described in patients with T1D. Hence, exploring HDL function, even in the presence of normal HDL-C levels, might provide additional insight into the underlying pathophysiology associated with increased CV risk in T1D. In the current review, we will provide a detailed overview of the current evidence for a role of HDL function as independent risk factor for the development of CVD in T1D.
Publisher: Hindawi Limited
Date: 2014
DOI: 10.1155/2014/898361
Abstract: Background . Obesity is a disorder often accompanied by a heightened state of systemic inflammation and immunoactivation. The present randomized crossover trial aimed to investigate the efficacy of curcumin, a bioactive polyphenol with established anti-inflammatory and immunomodulatory effects, on the serum levels of a panel of cytokines and mediators in obese in iduals. Methods . Thirty obese in iduals were randomized to receive curcumin at a daily dose of 1 g or a matched placebo for 4 weeks. Following a 2-week wash-out period, each group was assigned to the alternate treatment regimen for another 4 weeks. Serum s les were collected at the start and end of each study period. Serum levels of IL-1 α , IL-1 β , IL-2, IL-4, IL-6, IL-8, IL-10, VEGF, IFN γ , EGF, MCP-1, and TNF α were measured using a multiplex Biochip Array Technology based method. Results . Mean serum IL-1 β ( P = 0.042 ), IL-4 ( P = 0.008 ), and VEGF ( P = 0.01 ) were found to be significantly reduced by curcumin therapy. In contrast, no significant difference was observed in the concentrations of IL-2, IL-6, IL-8, IL-10, IFN γ , EGF, and MCP-1. Conclusions . The findings of the present trial suggested that curcumin may exert immunomodulatory effects via altering the circulating concentrations of IL-1 β , IL-4, and VEGF.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2016
Publisher: Termedia Sp. z.o.o.
Date: 02-08-2021
DOI: 10.5114/AOMS/140728
Abstract: In-stent restenosis (ISR) is an unfavorable outcome that occurs in patients after coronary stenting. Using of drugs like statins as well as drug-eluting stents has only been partially effective in reducing the rate of ISR. Since low high-density lipoprotein cholesterol (HDL-C) concentration is a pivotal cardiovascular disease risk factor, this study aimed the evaluation of the compositional and functional alterations of HDL in in iduals with ISR. This case-control study comprised 21 ISR, 26 non-ISR, 16 angiography-negative, and 18 healthy subjects. Serum HDL2 (d: 1.063-1.125 g/mL) and HDL3 (d: 1.125-1.210 g/mL) subfractions were extracted from each subject using sequential ultracentrifugation. The capacity of HDL to efflux cellular cholesterol from lipid-loaded macrophages as well as to uptake free cholesterol (FC) from triglyceride-rich lipoproteins (TGRL) during lipolysis were assessed. No difference was found in the HDL2 and HDL3 content of free cholesterol and total protein among the groups. NISR group showed reduced triglyceride content in HDL2 and increased phospholipid content in HDL3 relative to healthy subjects. Strong positive correlations were found between the cholesterol efflux capacity (CEC) of HDL2 and its phospholipid content in the healthy (r=0.50), angiography-negative (r=0.55) and ISR (r=0.52) groups. The capacity of apolipoprotein B (apoB)-depleted serum to uptake free cholesterol was not different among the groups Despite some compositional alterations, the capacity of HDL to efflux cholesterol from lipid-loaded macrophages as well as to uptake free cholesterol from TGRLs during lipolysis were not associated with ISR in this study
Publisher: Bentham Science Publishers Ltd.
Date: 08-2023
DOI: 10.2174/0929867329666220930114429
Abstract: To evaluate the immunogenic potential of the carrier-free peptide-based anti-PCSK9 (proprotein convertase subtilisin/kexin 9) vaccine in albino mice. The immunogenic pcsk9 peptide and 0.4% alum adjuvant were mixed thoroughly at a 1:1 ratio and used as a vaccine formulation. To assess the humoral immune response, animals' blood was s led two weeks after the last immunization. The ELISA method was employed to measure serum anti-PCSK9 antibody titers, PCSK9 concentrations, and PCSK9/LDLR interaction. ELISA analysis showed significant induction of IgG antibody titers by PCSK9 peptide vaccine in vaccinated mice sera compared to the control mice (in male and female mice were 12000±586 and 11566±642, respectively, p .001). Mechanistic analyses showed a significant reduction in serum PCSK9 concentrations by vaccine-induced antibodies in vaccine groups compared to the control groups (in male mice by 29±5 ng/mL (22.4%), p .001 and female mice by 26±5 ng / mL (21.0%), p .001). Serum concentrations of PCSK9 in control and vaccine groups were 131±8.6 ng / mL and 102±8.1 ng/ml in male mice and 124±6 ng/ml and 98±10 ng/ml in female mice, respectively. Moreover, vaccine-induced antibodies inhibited the PCSK9-LDLR interaction in male and female groups by 34% and 26%, respectively. No significant difference was detected between the male and female groups in all tests (p .05). According to our results, the PCSK9 peptide vaccine provoked the humoral immune system in albino mice to produce functional antibodies that inhibit plasma PCSK9. These effects were seen in both genders without any significant difference.
Publisher: Termedia Sp. z.o.o.
Date: 13-06-2023
DOI: 10.5114/AOMS/168120
Abstract: - The possible role of Urolithin A (UA) and Urolithin B (UB) on the induction of LDL uptake and the expression of its regulatory genes was eexplored using HepG2 cells and curcumin (20 uM), berberine (50 uM), UA (80 uM), and UB (80 uM) as the treatments in the experimental tests. The LDL uptake as well as cell-surface LDLR were higher in cells treated with UA in compari-son with cells treated with UB, and even in relation to the cells treated with curcumin and ber-berine as positive controls. In addition, cells treated with UB showed approximately 2 times greater LDLR expression levels compared with curcumin (FC: 2.144, P=0.013) and berberine (FC: 2.761, P=0.006). However, UA treatment resulted in significantly lower expression levels of LDLR compared with curcumin (FC: 0.274, P .001) and berberine (FC: 0.352, P=0.009). UB demonstrated approximately 8 times greater LDLR expression levels when compared with UA (FC:7.835, P=0.001). Compared with UB, as well as curcumin and berberine as positive controls, UA was more efficient in reducing PCSK9 expression levels. Although UB did not show any significant differences compared with curcumin and berberine, it illustrated higher levels of PCSK9 expression when compared with the UA group (FC: 3.694, P .001). The present results support that UA was more effective than UB in promoting LDL uptake as well as cell surface LDLR in HepG2 cells. This effect seems to be mostly mediated through the sup-pression of PCSK9 expression but not the induction of LDLR expression.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.EJPHAR.2021.174308
Abstract: Liposomes have been suggested as potential tools for cholesterol deposit mobilization from atherosclerotic lesions. Here, we explored the anti-atherosclerotic effects of phosphatidylserine (PS)-containing liposomes in vivo. High-fat diet-fed New Zealand white rabbits which were ided into groups receiving weekly intravenous injections of PS liposomes, atorvastatin-loaded PS (PSA) liposomes (100 μg phospholipid/kg), or control buffer for four weeks. The size and severity grade of atherosclerotic plaques as well as lipid profile were evaluated at the completion of study. In vitro, the expression and levels of anti ro-inflammatory genes and proteins, respectively, and macrophage cholesterol efflux capacity (CEC) of nanoliposomes were evaluated. Both PS and PSA lowered serum LDL-C (P = 0.0034, P = 0.0041) and TC (P = 0.029, P = 0.0054) levels but did not alter TG and HDL-C levels. Plaque size and grade were reduced by PS (P = 0.0025, P = 0.0031) and PSA (P = 0.016, P = 0.027) versus control. Moreover, intima-media thickness was significantly reduced in the PS vs. control group (P = 0.01). In cultured cells, ICAM-1 expression in the PS (P = 0.022) and VCAM-1 expression in the PS and PSA groups (P = 0.037, P = 0.004) were suppressed while TGF-β expression was induced by both PS and PSA (P = 0.048, P = 0.046). Moreover, CEC from macrophages to nanoliposomes was enhanced by PSA (P = 0.003). Administration of anionic PS-containing liposomes could improve lipid profile and promote plaque regression through mechanisms that may involve cholesterol efflux and modulation of adhesion molecules.
Publisher: Hindawi Limited
Date: 28-06-2022
DOI: 10.1155/2022/3577761
Abstract: Background. In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods. This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the activity of serum antioxidant enzymes such as glutathione peroxidase (GPx) and superoxide dismutase (SOD) were assessed by colorimetric methods. The overall oxidative burden was assessed using a pro-oxidant-antioxidant balance (PAB) assay. Results. MDA levels were considerably higher in the ISR group when compared to healthy subjects ( P = 0.004 ). PAB also indicated significantly higher values in both ISR ( P 0.001 ) and NISR ( P 0.001 ) groups related to healthy subjects. No significant differences were observed between the studied groups regarding thiol levels, antioxidant enzyme activities, and TAC. Multinomial logistic regression analysis showed that elevated serum levels of MDA (OR: 1.028, 95% CI: 1.008-1.048 P = 0.006 ) and PAB (OR: 1.076, 95% CI: 1.017-1.139 P = 0.011 ) were significantly associated with higher ISR risk however, increased values of TAC (OR: 0.990, 95% CI: 0.982-0.999 P = 0.030 ) were significantly associated with decreased ISR risk, while after adjustment for confounders, only SOD activity (OR: 0.0, 95% CI: 0.0-0.0 P 0.001 ) and PAB value (OR: 1.866, 95% CI: 1.856-1.900 P 0.001 ) showed association with ISR risk. Conclusion. According to the present findings, some oxidative and antioxidative markers like PAB and SOD activity showed the potential in the prediction of ISR risk.
Publisher: Termedia Sp. z.o.o.
Date: 28-09-2022
DOI: 10.5114/AOMS/154987
Abstract: Background: This study aimed to investigate the trehalose-induced alterations in serum expression levels of miRNAs associated with vascular inflammation in patients with coronary artery disease (CAD) in order to evaluate the effectiveness of intravenous (IV) trehalose administration in reducing arterial wall inflammation. Methods: This trial enrolled 14 men with a history of myocardial infarction (MI) and systemic inflammation. The patients were randomized in a 2:1 ratio to trehalose (15g/week, IV administration) (N=10) or placebo (equal volume 0.9% normal saline) (N=4) for a period of 12-weeks. The relative serum expression levels of miRNA-126, miRNA-24, miRNA-181b, miRNA-10a and miRNA-92a were assessed. Results: IV trehalose administration significantly increased the serum level of miRNA-24 (2.473±0.72 P=0.037) compared to the baseline, but did not alter the other miRNA serum levels. However, at the end of the study, miRNA-24 (4.58±0.99 P=0.002), miRNA-181b (4.08±1.75 P=0.009) and miRNA-10a (3.68±0.63 P=0.013) showed notably higher serum levels in the trehalose relative to the placebo group. Furthermore, the reduction (normalized to baseline) in serum levels of miRNA-126 (P=0.042) and miRNA-92a (P=0.001) were reduced in the trehalose versus placebo group, while the serum level of miRNA-24 (P=0.007) was notably higher than that in the placebo group. Conclusion: Serum levels of miRNAs associated with vascular inflammation were altered following IV trehalose administration. The alterations in serum miRNAs, especially miRNA-126 and miRNA-24, could be considered as helpful biomarkers for the evaluation of trehalose potency in reducing arterial wall inflammation in patients with CAD.
Publisher: The Sax Institute
Date: 2018
DOI: 10.17061/PHRP2841824
Abstract: The NSW (New South Wales) Climate Change Policy Framework, launched by the NSW Government in 2016, recognises that climate change presents risks to health and wellbeing. Risks to health and wellbeing come from direct impacts of extreme weather events, and from indirect impacts through effects on air, water, food and ecosystems. Responding to these challenges offers an opportunity to protect and promote health by enhancing environmental amenities, and building adaptive capacity and resilience in populations and systems. To develop policy that effectively protects and promotes health in the face of climate change in NSW it is necessary to define the expected impacts of climate change on health and wellbeing in NSW.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.DRUDIS.2017.09.014
Abstract: Recent studies have demonstrated that assessment of high-density lipoprotein (HDL) functionality indices, instead of HDL cholesterol measurement, is a more robust tool for the evaluation of the functional status of HDL and cardiovascular risk. There are qualitative abnormalities of HDL particles in familial hypercholesterolemia (FH) patients that might represent potential therapeutic targets. Despite the potential promise of optimizing HDL functionality for the treatment of FH, there has been no prior comprehensive review focusing on the impact of different lipid-modifying therapies on HDL functionality in FH patients. In the present review, we aim to fulfill this gap and provide a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH.
Publisher: MDPI AG
Date: 20-10-2019
DOI: 10.3390/JCM8101742
Abstract: Background: The results of several studies have suggested that infections and sepsis, either bacterial or viral, might be associated with elevated plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. Since there are no data on PCSK9 levels and antibiotic resistance or the severity of disease in patients with bacterial infections in intensive care units, the aim of this study was to investigate whether any such associations exist. Methods: 100 patients (46 males, mean age 67.12 ± 1.34 years) with bacterial infections who were staying in an intensive care unit (ICU) longer than 48 h but less than 7 days and who were not receiving corticosteroids were analyzed. Their serum levels of albumin, C-reactive protein, glucose, lactate, blood urea nitrogen, prothrombin (international normalized ratio), total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, PCSK9, and procalcitonin were measured. The severity of the patients’ condition was assessed by using the Glasgow Coma Scale (GCS), the Sequential Organ Failure Assessment (SOFA), and the Acute Physiology and Chronic Health Evaluation II (APACHE II) scales. Results: Using a hierarchical regression modeling approach, no significant association was found between PCSK9 levels and either the severity of disease (APACHE II, SOFA, and GCS) indices or resistance to antibiotics. Conclusion: The results suggest that there is no association between PCSK9 levels and resistance to antibiotics or the condition of patients hospitalized in intensive care units.
Publisher: Wiley
Date: 20-08-2018
DOI: 10.1002/JCB.27303
Abstract: Gene therapy is considered as a promising approach for treating cardiac dysfunction. In this review, we evaluated the clinical trials assessing gene therapy in cardiovascular diseases (CVD) from 2000 to 2017. PubMed and ClinicalTrials.gov (only English language) were searched for clinical trials published between January 2000 and May 2017, using the search terms “gene transfer” OR “gene therapy” and “cardiovascular diseases” and related terms. The trials with s le size lower than 10 patients were excluded. Twenty‐six clinical trials on human and animals, including 1543 patients were listed and evaluated. The s le size in 14 trials was lower than 100 patients and in seven trials lower than 20 patients. Eleven trials used plasmid DNA and eight trials used adenovirus, one study used plasmid DNA, adenovirus, and liposome. We detected that gene therapy was a safe approach and improved the symptoms of CVD however, the effect of gene therapy on the cardiac dysfunction is controversial.
Publisher: Elsevier BV
Date: 12-2020
Publisher: No publisher found
Date: 2019
DOI: 10.1002/JCB.28877
Abstract: Nonalcoholic fatty liver disease (NAFLD) as a prevalent hepatic disease is associated with an increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD). Lifestyle modification and good metabolic control is the first line of treatment, but not always efficacious in reversing NAFLD pathogenesis. Curcumin is a dietary phytochemical with hepatoprotective activities, though its low bioavailability is considered as a major challenge for clinical applications. Therefore, in this study, in order to improve the bioavailability of curcumin, it was coadministered with piperine and we investigated the effects of this bioavailability-enhanced curcumin on serum hepatic enzymes, lipid profile, and glycemic indices in patients with NAFLD. In this randomized controlled parallel-group trial, 70 subjects with ultrasound-determined NAFLD were randomized to either 500 mg curcuminoids coadministered with 5 mg piperine daily or placebo for 12 weeks. NAFLD severity (on the basis of sonography) and hepatic function was assessed at baseline and at the study end. Seventy subjects completed the study. Supplementation with curcuminoids plus piperine significantly reduced the hematocrit (P = 0.027), erythrocyte sedimentation rate (P = 0.048) and the serum concentrations of alanine aminotransferase (P = 0.035), aspartate aminotransferase (P = 0.042), alkaline phosphatase (P = 0.004), cholesterol (P < 0.016), low-density lipoprotein cholesterol (P < 0.017), Iron (P = 0.026), and Hemoglobin (P = 0.025) and increased total iron-binding capacity (P = 0.003). However, except albumin, changes in other parameters were not statistically different between groups. In addition, administration of curcuminoids plus piperine significantly improved NAFLD severity (P < 0.001), which was statistically different compared with the placebo group (P = 0.022). Also, the percentage of improved patients was marginally higher in the curcuminoids plus piperine group when compared with the placebo group (P = 0.058). This study suggested beneficial effects of combined curcuminoids and piperine supplementation on disease severity in patients with NAFLD.
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
No related grants have been discovered for Shiva Ganjali.