Exploring the Therapeutic Potential of Apigenin in Obesity-Associated Fibrinolytic Dysfunction: Insights From an Animal Study.

INTRODUCTION: Obesity (Obe) is a chronic metabolic disorder usually complicated by impaired fibrinolytic activity. Apigenin (Api) is one of the flavonoids that have anti-adiposity effects. This study aimed to explore the therapeutic potential of Api in high-fat diet (HFD)-induced obese rats. METHODS: Twenty-four Wistar adult male rats were randomly allocated into control group, supplemented with a normal pellet diet (NPD); Api group, supplemented with Api (10 mg/kg) for eight weeks; Obe group, obesity was induced by feeding HFD for eight weeks; and Obe/Api group, obese rats supplemented with Api for eight weeks. Body mass index (BMI), homeostatic model assessment of insulin resistance (HOMA-IR), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), total superoxide dismutase (t-SOD) activity, and plasminogen activator inhibitor-1 (PAI-1) were measured. RESULTS: Compared to the control group, Obe group exhibited a significant increase in BMI, HOMA-IR, TNF-α, MDA, and PAI-1. These results were also associated with a significant decrease in serum t-SOD activity. Supplementation of Api alleviated the measured deteriorated parameters and ameliorated visceral adiposity in obese rats. CONCLUSION: This study provides compelling evidence regarding a promising role for Api in ameliorating the impairment of fibrinolytic activity in an Obe animal model. The observed effects are likely mediated through Api's anti-obesity properties, as well as its indirect modulation of PAI-1, oxidative stress, and inflammation. Future clinical studies are recommended that may make benefit of the preclinical therapeutic use of apigenin in obesity-associated fibrinolytic dysfunctions.

Vitis vinifera leaf extract liposomal Carbopol gel preparation's potential wound healing and antibacterial benefits: in vivo, phytochemical, and computational investigation.

Vitis vinifera Egyptian edible leaf extract loaded on a soybean lecithin, cholesterol, and Carbopol gel preparation (VVL-liposomal gel) was prepared to maximize the in vivo wound healing and anti-MRSA activities for the crude extract, using an excision wound model and focusing on TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1ß, and MRSA (wound infection model, and peritonitis infection model). VVL-liposomal gel was stable with significant drug entrapment efficiency reaching 88% ± 3, zeta potential value ranging from -50 to -63, and a size range of 50-200 µm nm in diameter. The in vivo evaluation proved the ability of VVL-liposomal gel to gradually release the drugs in a sustained manner with greater complete wound healing effect and tissue repair after 7 days of administration, with a significant decrease in bacterial count compared with the crude extract. Phytochemical investigation of the crude extract of the leaves yielded fourteen compounds: two new stilbenes (1, 2), along with twelve known ones (3-14). Furthermore, a computational study was conducted to identify the genes and possible pathways responsible for the anti-MRSA activity of the isolated compounds, and inverse docking was used to identify the most likely molecular targets that could mediate the extract's antibacterial activity. Gyr-B was discovered to be the best target for compounds 1 and 2. Hence, VVL-liposomal gel can be used as a novel anti-dermatophytic agent with potent wound healing and anti-MRSA capacity, paving the way for future clinical research.

Volumetric bone mineral density and serum 25-hydroxyvitamin D status in the UK dwelling Arab, Caucasian, and South Asian women.

Objectives: Little is known about ethnic differences in bone geometry, nor their association with 25-hydroxyvitamin D (25(OH)D), especially among ethnicities living in the same country. The purpose of this preliminary study was to investigate differences in bone geometry at the radius and tibia, as well as in 25(OH)D status, between Arab (A), South Asian (SA), and Caucasian (C) premenopausal women residing in the UK. The potential association between 25(OH)D concentration and indices of bone geometry was also assessed. Methods: Fifty-seven healthy premenopausal women (17 A, 18 SA, and 22 C), ranging in age from 18 to 51 years, underwent assessment of their volumetric bone mineral density and 25(OH)D concentration. Ethnic differences were assessed using ANOVA. Spearman's rho was used to analyze associations between 25(OH)D and pQCT bone variables. Results: At the 4% radius, Arab women had a lower BMC, as well as a smaller total bone area and trabecular area than did Caucasian women. At the 4% tibia, Arab women had a lower total vBMD than did South Asian women. Serum 25(OH)D among Arab (36.5(22.4SD)) and South Asian (31.4 (16.8SD)) women was significantly lower than in Caucasian women (81.9(20.0SD)) (P < 0.05). There were no statistically significant correlations between 25(OH)D and pQCT bone variables in any ethnic group. Conclusions: This study suggests a possible need for attention to bone health in premenopausal Arab women as well as improvement in Vitamin D status in Arab and South Asian populations.

Is Vitamin B12 Level a Reliable Predictor of Psychosis Severity in Male Patients with Megaloblastic Anemia at a Single Tertiary Hospital?

Background: Megaloblastic anemia (MA) occurs due to ineffective erythropoiesis, which results from impaired DNA synthesis in the hematopoietic precursors and intramedullary hemolysis. MA's most common cause is nutritional deficiencies of either cobalamin (vitamin B12) or folate (vitamin B6). This study aims to determine the association between MA caused by vitamin B12 deficiency and psychosis among psychotic male patients in Mental Health Hospital at Taif, Saudi Arabia. Methods: Fifty psychotic male patients, aged 48.58±1.72, were recruited from the Mental Health Hospital at Taif, Saudi Arabia, in addition to 54 sex-matched healthy controls. The following tests were run: complete blood count (CBC), liver function tests (LFT), serum levels of vitamin B12, folate, and C-reactive protein (CRP). Results: The CBC showed that RBCs count, haemoglobin, haematocrit, platelets count, mean platelets volume (MPV), and absolute lymphocyte count were significantly lower in psychotic patients versus healthy controls (P=0.007, P=0.002, P=0.001, P=0.004, P=0.0001, and P=0.005, respectively). In contrast, the eosinophil absolute count and basophil percentage were significantly higher in psychotic patients versus controls (P=0.009, P=0.0001, respectively). Vitamin B12 levels were insignificantly decreased in psychotic patients versus healthy group. There were significant negative correlations between serum levels of VitB12 and negative symptoms (r=-0.381, P=0.006) and hallucination (r=-0.297, P=0.036). Conclusion: These findings indicate no link between MA induced by VitB12 insufficiency and psychosis among psychotic patients. However, low serum VitB12 can predict the severity of some psychosis signs, including hallucinations and negative symptoms. Therefore, monitoring VitB12 levels and its supplementation in psychotic patients is recommended to improve their symptoms.

Angiogenesis Biomarkers in Ischemic Stroke Patients.

INTRODUCTION: Stroke is a global health issue, and ischemic stroke is among the most common strokes affecting many people worldwide. Throughout ischemic stroke, various immune cells counter its effect by releasing cytokines, chemokines, and angiogenic molecules. These molecules can work as potential biomarkers in the diagnosis and monitoring of the progress of ischemic stroke. The current study investigated the use of angiogenic molecules as biomarkers in ischemic stroke patients. METHODS: The samples were obtained from twenty healthy subjects and nineteen patients with ischemic stroke. Multiplex assay was used to measure the serum levels of angiogenic biomarkers, including endoglin, VEGF-A, endothelin-1, G-CSF, and angiopoietin-2. All data were analyzed using an unpaired Student's t-test. Correlations between measured parameters were made using Pearson correlations. RESULTS: Angiopoietin-2, VEGF-A, endothelin-1, and endoglin levels in stroke patients were significantly higher compared to healthy controls. Nevertheless, G-CSF level showed a non-significant increase in patients compared to controls. The correlation coefficient of measured angiogenic biomarkers among patients showed significant correlations between endoglin, angiopoietin, VEGF-A, and endothelin-1. DISCUSSION: The angiogenic factors were significantly increased in patients with ischemic stroke, which may help in the early detection of ischemic stroke and consequently prompt treatment and better prognosis.

Altered Expression of Angiogenic Biomarkers in Pregnancy Associated with Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) typically occurs during the third trimester of pregnancy. Maternal hyperglycemic may influence the expression of pro-and anti-angiogenic factors. Altered levels of angiogenic biomarkers in GDM pregnant women are associated with abnormal placentation. This study aimed to investigate the rates of expression of five angiogenic biomarkers called vascular endothelial growth factor-A (VEGF-A), angiopoietin-2, endoglin, endothelin-1, and granulocyte colony-stimulating factor (G-CSF) in GDM. METHODS: The samples were obtained from normal (n=9) and GDM (n=10) pregnancies. Multiplex assay was used to assess the levels of angiogenic biomarkers including VEGF-A, endoglin, endothelin-1, angiopoietin-2, and G-CSF in serum samples. All data were statistically analyzed using an unpaired Student's t-test. Correlations between measured parameters were made using Pearson correlations. RESULTS: VEGF-A, endoglin, endothelin-1, and angiopoietin-2 levels in GDM were significantly higher (P value = 0.001, 0.042, 0.049, 0.001; respectively) compared to control. However, G-CSF level exhibited a non-significant increase (P=0.466) in GDM compared to healthy controls. There was a significant positive correlation between angiopoietin-2 with endoglin, endothelin-1, and VEGF-A. Moreover, there was a significant positive correlation between VEGF-A with endoglin and endothelin-1. Most interestingly, there was a significant positive correlation between G-CSF with endothelin-1. CONCLUSION: The angiogenic biomarkers were highly altered in pregnant women with GDM. The study provides a novel advance in the field of gestational diabetes, in terms of increase of angiogenic factors that can modify the vascularization of the placenta, the development of fetal vascular system and the insulin resistance itself.

Synergistic inhibitory effect of capsaicin and dihydrocapsaicin on in-vitro platelet aggregation and thromboxane formation.

: Capsaicinoids, including capsaicin (CAP) and dihydrocapsaicin (DHC), the pungent principles of pepper fruits, individually inhibit in-vitro platelet aggregation. However, their effects, when present together, are not known. The aims of this study were to compare the effects of CAP and DHC alone, and in combination in the ratio that they are found in chilies (∼60% CAP : 40% DHC), on in-vitro platelet aggregation, platelet count and thromboxane B2 (TXB2) formation. The effects of 12.5 and 6.25 µmol/l CAP and DHC individually, and in combination (CAP : DHC, 60 : 40) on arachidonic acid-induced, ADP-induced and collagen-induced aggregation, were investigated. Platelet count was determined preincubation and postincubation with CAP and DHC and in combination. TXB2 formation from platelets treated with arachidonic acid in the absence and presence of CAP and DHC individually, and in combination, was measured. Compared with control, CAP and DHC (12.5 µmol/l) inhibited arachidonic acid-induced aggregation by 23.2 and 25.3%, respectively (both P < 0.01). In combination, CAP and DHC exhibited further inhibition in arachidonic acid-induced aggregation (CAP : DHC, 3.75 : 2.5 µmol/l, 36.5%, P = 0.01; 7.5 : 5 µmol/l, 57.5%, P < 0.001), compared with control. Incubation of platelets with caspaicinoids did not significantly affect the platelet count. In addition, the CAP : DHC (7.5 : 5 µmol/l) combination significantly inhibited (P < 0.001) TXB2 formation, compared with the individual capsaicinoids. Capsaicinoids had no effect ADP-induced or collagen-induced aggregation. The combination of CAP and DHC produces a significantly greater inhibitory effect on arachidonic acid-induced platelet aggregation and subsequent TXB2 formation, compared with the individual capsaicinoids.

Inhibition of platelet aggregation by vanilloid-like agents is not mediated by transient receptor potential vanilloid-1 channels or cannabinoid receptors.

Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the individual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of individual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors.

Vanilloid-like agents inhibit aggregation of human platelets.

INTRODUCTION: Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents. MATERIALS AND METHODS: The effects of plant-derived (capsaicin; dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA; N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10µM), collagen (4, 8µg/mL) and arachidonic acid (AA, 300, 400µg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay. RESULTS: Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA. CONCLUSIONS: These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.