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Papers by VIOLET KASABRI

Jordan Journal of Pharmaceutical Sciences, Jul 24, 2023

Background and Aims: Zonulin, carnitine, choline, -butyrobetaine (-BB), and trimethylamine N-ox... more Background and Aims: Zonulin, carnitine, choline, -butyrobetaine (-BB), and trimethylamine N-oxide (TMAO) are intricately involved in metabolic anomalies and type 2 diabetes mellitus (T2D). This study aimed to compare and correlate the plasma levels of zonulin, carnitine, choline, -butyrobetaine, and TMAO, along with the adiposity, atherogenicity, surrogate insulin resistance (sIR), and proinflammatory hematological indices of newly diagnosed drug-naive pre-diabetic and diabetic patients vs. apparently healthy normoglycemic controls. Methods: In a cross-sectional study, 30 normoglycemic subjects (controls) and 16 pre-diabetic (PreDM) and 14 type 2 diabetes (T2D) cases, that were gender and age-matched, were enrolled. Zonulin, carnitine, choline, -BB, and TMAO plasma levels were appraised using colorimetric assays. A comparison between the study groups was conducted by ANOVA while Spearman rank correlations between the metabolic risk biomarkers and between the risk markers and adiposity, sIR, atherogenicity, and proinflammatory hematological indices were also examined. Results: Significant intergroup discrepancies in plasma carnitine, choline, -BB, and TMAO (but not zonulin) could be recognized in the cases vs. controls. Fasting blood glucose (FPG), glycated hemoglobin (A1C), triglycerides (TG), body mass index (BMI), lipid accumulation product (LAP), visceral adiposity index (VAI), atherogenic index of plasma (AIP), and all sIR were outstandingly higher in the cases vs. controls. Blood indices lacked a scoring value to discriminate cases from controls. Inadvertently, no relation was found between plasma carnitine, choline, -BB, TMAO, or zonulin in cases. Among the rest of the markers and sIR indices; The triglyceride-glucose-body mass index (TyG*BMI) related reciprocally to zonulin. Noticeably, among adiposity indices, TyG*BMI, triglyceride glucose-waist circumference (TyG*WC), and metabolic score for insulin resistance (MetS-IR) positively associated with waist circumference (WC), hip circumference (HC), BMI, body adiposity index (BAI), and waist-to-height ratio (WHtR). Exceptionally LAP proportionally correlated with all sIR. TyG*WC and MetS-IR correlated directly with the conicity index (CI). WHR directly associated with triglyceride-glucose (TyG) index and TyG*WC. Remarkably, the TyG index (but not TyG*BMI, TyG*WC, or MetS-IR) positively associated with all atherogenicity indices and RDW (but none of other blood indices). TMAO correlated inversely (P < 0.05) and moderately with choline. Distinctively, carnitine associated negatively with TC (P < 0.05). Both choline and carnitine related similarly and directly with PLR but inversely with lymphocytes (p <0.05). Effectively, Butyrobetaine associated with both WC and the TyG-WC index equally negatively (P < 0.05). Substantially, Butyrobetaine correlated inversely with both atherogenic LDL-C/HDL-C ratio and MPV (P < 0.05). No pronounced relations were detected between the five microbiome signature determinants and glycemic control parameters (FBG and A1C %), sIR (TyG, TyG-BMI or MetS-IR), adiposity (WHR, WHtR, CI, BAI, LAP, or VAI), atherogenicity indices (TC/HDL-C ratio, non-HDL-C/HDL-C ratio, or AIP), or blood indices (NLR or MLR).Conclusion: Given the intergroup discrepancies in sIR, plasma zonulin, carnitine, choline, -BB, and TMAO along with their elective correlations with indices and clinical parameters of metabolic dysregulations, our study cannot rule out any possible molecular crosstalk and interplay of the biomarkers studied with the pathophysiology of prediabetes/diabetes. All in all, plasma zonulin, carnitine, choline, -BB, and TMAO with sIR can be putative surrogates for molecular cardiometabolic risk biomarkers to use as prognostic/predictive tools for the diagnosis/prevention and potential targets for prediabetes/diabetes management modalities.

Hormone Molecular Biology and Clinical Investigation, Nov 29, 2018

Background: Pentraxin-3 (PXT-3) and cystatin-C (Cys-C) are robustly related with central obesity ... more Background: Pentraxin-3 (PXT-3) and cystatin-C (Cys-C) are robustly related with central obesity and insulin resistance in prediabetes/metabolic syndrome (preDM-MetS). This cross-sectional study aimed to compare and correlate PXT-3 and Cys-C plasma levels in 29 normoglycemic MetS patients, 30 newly diagnosed drug naive preDM-MetS cases vs. 29 normoglycemic lean controls. Results: Unlike PXT-3; Cys-C level was significantly higher in normoglycemic MetS (but not preDM-MetS) vs. healthy controls. Except for fasting blood glucose (FBG) and HbA 1c ; no further intergroup discrepancy could be identified between the MetS arms. Adiposity indices [body mass index (BMI), waist circumference (WC), hip circumference (HC), waist/height ratio (WHtR), body adiposity index (BAI) and lipid accumulation product (LAP) but not conicity index (CI)], atherogenicity index of plasma (AIP) (but not non-high density lipoprotein-cholesterol (nonHDL)-C, non-HDL-C/HDL-C ratio or total cholesterol (TC)/HDL-C ratio) or any of blood indices were substantially higher in both MetS (normoglycemic and preDM) groups vs. controls. Low density lipoprotein (LDL)-C/HDL-C ratio, visceral adiposity index (VAI) and WHR were exceptionally greater in MetS-preDM vs. controls. Marked proportional PTX-3-Cys-C correlation was noted in 59 MetS participants (normoglycemic and preDM). PTX-3 (but not Cys-C) correlated proportionally with each of neutrophils, monocyte/lymphocyte ratio and neutrophil/lymphocyte ratio but inversely with the lymphocyte count. Substantially, Cys-C (but not PXT-3) positively associated with both VAI and AIP but inversely with HDL-C. Neither biomarker in MetS pool had relations with red blood cell distribution width-coefficient of variation (RDW-

Food and Nutrition Sciences, 2013

OBJECTIVE-Obesity and type 2 diabetes are national and worldwide epidemics. Because currently ava... more OBJECTIVE-Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies. RESEARCH DESIGN AND METHODS-Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus. RESULTS-Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Fourweek administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1's antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis. CONCLUSIONS-These results identify Rb1 as an antiobesity and antihyperglycemic agent.

Research Square (Research Square), Mar 13, 2023

Aims and methods This study aimed to compare and correlate pharmacotherapy biomarkers' plasma and... more Aims and methods This study aimed to compare and correlate pharmacotherapy biomarkers' plasma and salivary levels (appraised using colorimetric assays of Lipocalin, Nesfatin, Omentin, Oxytocin, RBP-4 (retinol-binding protein-4), Resistin, SIRT 1 (sirtuin 1), Visfatin and ZBED3 (zinc nger, BED-type (ZBED) protein 3), adiposity, and atherogenicity indices in 61 normoglycemic and newly diagnosed drug naive pre-diabetic (PreDM) MetS (metabolic syndrome) patients vs. 29 lean, and normoglycemic controls. Intergroup Comparisons was conducted by ANOVA. Spearman rank correlation was also examined. Results About three quarters of the participants were females, with gender distribution similar between the two study groups (P = 0.585). Among MetS patients, almost half were normoglycemic, about 43% were prediabetic and about 8% were diabetic. The average age of study participants was 48.6 years, with MetS group being signi cantly older than the control group (P < 0.001). In accordance to the study selection criteria, glycemic (FPG and A1c) and lipid parameters (TG, HDL-C and non-HDL-C), adiposity indices (BMI, WHR, WtHR, C-index, BAI, LAP, VAI) and atherogenicity indices (AIP, TC/HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C and TG/HDL-C) were all signi cantly higher in the MetS group compared to the control group (P < 0.05). Among the plasma cardiometabolic risk biomarkers of pharmacotherapy, plasma (but not salivary) lipocalin levels and Salivary nesfatin (unlike plasma nesfatin) were signi cantly higher P < 0.05) in the MetS group compared to the normoglycemic lean controls. Notably, plasma SIRT1 levels were pronouncedly greater (P < 0.05) in MetS recruits in comparison to control's levels. Conversely; salivary SIRT1 concentrations in MetS pool markedly exceeded those of controls' salivary levels. Oddly and collectively salivary and blood levels of omentin, oxytocin, RBP-4, resistin, visfatin and ZBED3 lacked comparably pronounced discrepancies in MetS cases vs. those of study controls. Exceptionally oxytocin, amongst 9 cardiometabolic risk biomarkers of pharmacotherapy studied, had proportional signi cant correlations between plasma and saliva levels, in both total sample and MetS patients (P < 0.05). Plasma OXT in the total sample correlated signi cantly though inversely with both SBP and FBG (unlike salivary OXT). Interestingly of MetS pool; markedly Proportional correlations of plasma (but not salivary) OXT with TG, and adiposity indices of LAP and VAI, and all atherogenecity indices were delineated. Collectively both blood and saliva OXT in the total study pool, as well as the remaining biomarkers; lacked comparably substantial associations with both adiposity and atherogenecity indices and clinical parameters of fasting lipid pro le.

Bratislavské lekárske listy, 2019

OBJECTIVES: The neuropeptide hormone-Oxytocin (OXT) and glycoprotein Lipocalin-2 (LCN-2) are stro... more OBJECTIVES: The neuropeptide hormone-Oxytocin (OXT) and glycoprotein Lipocalin-2 (LCN-2) are strongly associated with cardiometabolic risks of insulin resistance in metabolic syndrome (MetS) and prediabetes (preDM). METHODS: In a cross sectional design we aimed to compare and correlate plasma levels of OXT and LCN-2 and a set of clinical parameters, adiposity indices, atherogenicity indices, and hematological indices in 29 MetS/ preDM individuals and 29 non-diabetic MetS subjects vs 30 normoglycemic lean controls. Colorimetric enzymatic assays of biomarkers were procured. RESULTS: LCN-2 concentration (ng/mL) increased signifi cantly in MetS/preDM vs controls. Substantially in MetS recruits (both non-diabetic and pre-diabetics; n = 58); OXT directly correlated with visceral adiposity index (VAI), non-HDL-C/HDL-C ratio, TC/HDL-C ratio, LDL-C/HDL-C ratio, lipid accumulation product (LAP), and atherogenicity index of plasma (AIP). Impressively, LCN-2 correlated proportionally with waist circumference (WC), red cell distribution width (RDW), neutrophils, and neutrophils to lymphocytes ratio (NLR), but inversely with lymphocytes in the 58 (non-and preDM) MetS participants. CONCLUSIONS: These pronounced variations and correlations of OXT and LCN-2 emphasize their putative molecular roles in MetS and preDM pathophysiologies. Thus, OXT and LCN-2 can be surrogate prognostic/diagnostic tools for the MetS/preDM pharmacotherapy/prevention (Tab. 3, Fig. 1, Ref. 44).

Emblica officinalis stimulates the secretion and action of insulin and inhibits starch digestion and protein glycation

12th European Congress of Endocrinology, Apr 1, 2010

In vitro Modulation of Pancreatic Insulin Secretion and Extra Pancreatic Insulin Action, Enzymatic Starch Digestion and Protein Glycation by Terminalia chebula Extracts

European journal of medicinal plants, Jan 10, 2014

Romanian Journal of Diabetes Nutrition and Metabolic Diseases, Sep 30, 2020

Introduction: Osteocalcin (OCN) and Sirtuin 1 (SIRT1) are intricately involved in metabolic syndr... more Introduction: Osteocalcin (OCN) and Sirtuin 1 (SIRT1) are intricately involved in metabolic syndrome (MetS) and prediabetes (PreDM) anomalies and derangements. In a heterogeneous pool of nondiabetic and preDM MetS recruits, adiposity, atherogenicity and blood indices, SIRT1 and OCN were compared to the respective parameters in normoglycemic and lean controls. Further testing of putative relationships between indices and markers was performed in 59 patients with MetS. Material and Methods: In this cross-sectional study, comparisons and correlations were undertaken for biomarkers, adiposity, atherogenicity and hematological indices in 29 MetS-normoglycemic and 30 newly diagnosed drug-naive MetS-preDM patients versus 29 lean, healthy and normoglycemic controls. ANOVA and Spearman rank correlations were used for statistical comparisons. Results: OCN level (OCN; ng/mL) was significantly higher in normoglycemic MetS vs. both MetS-PreDM and controls (28.13±1.22 and 26.02±3.2 vs. 23.3±3.19, P<0.001 respectively). In contrast, the circulating level of SIRT1 (ng/mL) was lower in both normoglycemic and preDM MetS vs. healthy controls (1.42±0.47 and 1.64±0.58 vs. 3.88±0.95; P<0.001, respectively). Except for fasting plasma glucose and glycated hemoglobin (A1C), no further intergroup discrepancy could be identified between normoglycemic-MetS and preDM-MetS. Notably, adiposity indices and the atherogenicity index of plasma were significantly higher in both MetS (normoglycemic and preDM) groups vs. controls. The LDL-C/HDL-C ratio, visceral adiposity index, and waist/hip ratio were higher only in MetS-preDM vs. controls. In the MetS pool (n=59), OCT, but not SIRT1, was associated reciprocally with fasting glycemia and A1C, monocyte/lymphocyte ratio, but proportionally with HC. In the same MetS pool, SIRT1 correlated significantly positively with TG, lipid accumulation product, visceral adiposity index and the atherogenicity index of plasma. Conclusions: OCN and SIRT1 may reciprocally participate in the development of MetS and preDM; both biomarkers may be putatively surrogate diagnostic/prognostic tools for metabolic anomalies prediction/prevention and pharmacotherapy.

Asian Pacific Journal of Cancer Prevention

Evaluation of correlations of Plasma Levels of Oxytocin, Omentin-1 and Irisin in Diabetic and Non-Diabetic Metabolic Syndrome Patients: A Cross Sectional Study in Jordan

Jordan Medical Journal, 2017

Metabolic syndrome (Mets) risk factor biomarkers, namely oxytocin (OXT), omentin-1 and irisin, pl... more Metabolic syndrome (Mets) risk factor biomarkers, namely oxytocin (OXT), omentin-1 and irisin, plasma levels were evaluated via colorimetric enzymatic bioassays. A total of 195 Mets patients were recruited from the outpatients’ diabetes and endocrinology clinics at the National Center for Diabetes Endocrinology and Genetics. Participants were subdivided according to their fasting glycemia status into either the normoglycemic subjects group (Mets-controls) or dysglycemic subjects group (Metspre/ T2DM). Enrolled recruits in both study arms were BMI (body mass index)-, gender- and agematched. Distinctively in the Mets-pre/T2DM group; mean circulating levels of both OXT (pg/mL) and omentin-1 (ng/mL) were significantly lower but mean irisin plasma levels (ng/mL) were substantially higher (p<0.01 vs. respective Mets-controls'). Markedly, in the total pool of Mets-participants, plasma OXT levels correlated inversely with irisin plasma levels but proportionally with omentin-1 plasma ...

Analytical Chemistry Letters, 2020

New synthetic 36 fluoroquinolones (FQs) have been developed. Their anti-inflammatory and 2,2-diph... more New synthetic 36 fluoroquinolones (FQs) have been developed. Their anti-inflammatory and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-and nitric oxide (NO)-radicals scavenging propensities were delineated in vitro. The anti-inflammation related NO radical scavenging bioactivities of new FQs compounds against lipopolysaccharide (LPS)-prompted NO production in RAW 264.7 macrophages were examined using the Griess assay. Selectively nitro FQ compound 2-AnisCEtA exerted an exceedingly superior anti-inflammatory effects (p<0.001 vs. indomethacin IC 50 value of 103.35±4.4 μM) while 7 nitro FQs, 10 reduced FQs and 9 triazolo FQs were moderately more efficacious than indomethacin. The remaining 9 Compounds could display appreciable anti-inflammatory capacity. Unequivocally their DPPH radical scavenging effects were of substantially lesser efficacy than ascorbic acid. Using 400 μM methylglyoxal as the choice glucotoxicity concentration in RAW264.7 macrophages; it was shown that 18 out of 36 FQs could exhibit an exceedingly more superior than or significantly comparable cytoprotection against methylglyoxal-induced carbonyl toxicity to antiglycation aminoguanidine. Suggestively dual modulation of glycation-inflammation can be linked with FQs lipophilicity-chelating properties. FQs can serve as scaffolds for the development and designing of new druggable deglycation and antiglycation therapeutic candidates via duality of antiglycation-antiinflammatory capacities.

International Journal of Diabetes in Developing Countries, 2018

Ghrelin is deregulated in obesity-associated insulin resistance (IR) while visfatin features a ro... more Ghrelin is deregulated in obesity-associated insulin resistance (IR) while visfatin features a role in glucose uptake regulation, inflammation and IR. This study aimed to conduct comparisons and correlations of ghrelin and visfatin plasma levels in nondiabetic metabolic syndrome (MetS) and MetS-prediabetic/type 2 diabetes mellitus (T2DM) patients. In a cross-sectional study of 30 normoglycemic lean subjects (control), 31 MetS subjects, and 30 MetS-prediabetic/T2DM, plasma ghrelin and visfatin were measured by colorimetric-enzymatic assays. The comparison of both biomarkers between study groups and the correlation between them as well as with participants' adiposity, hematologic, and atherogenicity indices were conducted. Ghrelin levels (pg/mL) lacked any statistically significant difference between each of nondiabetic MetS (618.10 ± 93.22, p = 0.103) or MetS-pre/T2DM (498.17 ± 103.21, p = 0.454) vs. the normoglycemic lean control (369.38 ± 111.76). Visfatin level (ng/mL) in MetS patients with pre/T2DM (19.24 ± 2.05, p = 0.003) or without pre/T2DM (18.43 ± 1.83, p = 0.002) was significantly higher as compared to healthy controls' (8.62 ± 2.23). There was a direct ghrelin-visfatin correlation in the whole study population as well as in both MetS and MetS-pre/T2DM arms (p < 0.001). In nondiabetic MetS patients, ghrelin and visfatin proportionally correlated with waist/hip ratio (WHR; p = 0.032 vs. p = 0.008, respectively) while ghrelin correlated directly with BMI (p = 0.034). In MetS-pre/T2DM, visfatin correlated directly with body adiposity index (p = 0.039) but inversely with WHR (p = 0.011), while ghrelin and visfatin directly correlated with mean platelet volume (p = 0.025 vs. p = 0.030, respectively) and ghrelin proportionally correlated with platelet/lymphocyte ratio (p = 0.034). In effect, ghrelin and visfatin molecular interplays with adiposity and blood indices in the MetS derangements may present potential pharmacotherapeutic targets in metabolism and prediabetes anomalies.

Hormone Molecular Biology and Clinical Investigation

Objectives In this hypothesis paper we explore the underlying mechanisms for long-COVID and how t... more Objectives In this hypothesis paper we explore the underlying mechanisms for long-COVID and how the oxytocinergic neurones could be infected by SARS-CoV-2 leading to a reduction in plasma oxytocin (OXT). Furthermore, we aim to review the relevance of OXT and hypothalamic function in recovery from long-COVID symptoms and pathology, through exploring the pro-health effects of the OXT neuropeptide. Methods A review of published literature was surveyed using Google Scholar and PubMed. Results Numerous experimental data can be shown to correlate with OXT and long-COVID symptoms and conditions, thus providing strong circumstantial evidence to support our hypothesis. It is postulated that the reduction in plasma OXT due to acute and post-viral damage to the hypothalamus and oxytocinergic neurones contributes to the variable multi-system, remitting and relapsing nature of long-COVID. The intranasal route of OXT application was determined to be most appropriate and clinically relevant for th...

Epidemiology and Infection, Jan 23, 2013

The prevalence of natural carriage and molecular epidemiology of methicillin-resistant Staphyloco... more The prevalence of natural carriage and molecular epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MR-CoNS) isolates in a Jordanian community were investigated. The MRSA nasal carriage rate in 227 healthy volunteers was 7. 5 % and the majority (81 %) of MRSA harboured the resistance element SCCmec type IVe and were of a novel spa type t9519 (76 %) ; other significant spa gene types were t223 (14. 7%) and t044 (5. 9 %). All MRSA isolates were susceptible to other classes of antibiotics, and tested positive for at least three virulence factor encoding genes, but only two harboured the pvl gene. MR-CoNS carriage was 54. 2% and these isolates were characterized by single, double and untypable SCCmec elements, with Staphylococcus epidermidis SCCmec type IVa predominating. Of eight subjects with nasal co-colonization of MR-CoNS+MRSA, three shared SCCmec type IV in both groups of organisms. This is the first report of methicillin-resistant staphylococci carriage in a Jordanian community and its findings are important for epidemiological study and infection control measures of these organisms.

Preparation, Physicochemical Characterization and Biological Evaluation of some Hesperidin Metal Complexes

PubMed, 2014

The ability of hesperidin (HP) to form complexes with five metals; cobalt, nickel, zinc, calcium ... more The ability of hesperidin (HP) to form complexes with five metals; cobalt, nickel, zinc, calcium and magnesium was investigated. The complexation was studied using U.V spectroscopic titration, in methanol as well as aqueous buffer solutions (physiological conditions). Potential complexes were studied by IR and NMR spectroscopy, melting point and their solubility were also evaluated. The interaction of HP and its metal complexes with DNA was investigated by U.V spectroscopy. HP and its potential complexes were also tested for their ability to inhibit alpha amylase and alpha glucosidase enzymes. The results indicated that HP can form 1:1 complexes with cobalt, nickel and zinc in methanolic solution but not in aqueous buffers. Both HP and its metal complexes were found to intercalate DNA, at physiological condition, with preference to GC rich sequences. HP-metal complexes appeared to have higher affinity towards poly A DNA than the free HP. Neither HP nor its complexes exhibited antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa or Candida albicans. Results showed that HP has little inhibitory action on glucosidase and amylase enzymes with no obvious effect of complexation on the behavior of free HP. In conclusion HP was shown to form 1:complexes with the studied metal in methanol but not in aqueous buffer solutions. In presence of DNA however, complex formation in aqueous solutions seem to be encouraged with differential effect between the complexes and free HP.

Jordan Journal of Pharmaceutical Sciences, Sep 29, 2021

OBJECTIVES: Uric acid (UA) has a role in pathogenesis of several metabolic abnormalities includin... more OBJECTIVES: Uric acid (UA) has a role in pathogenesis of several metabolic abnormalities including insulin resistance (IR) and their related disorders. The aim of this report is to review the available evidences that reveal the association between UA, IR and related disorders via both noninsulin and insulin-based IR indices. METHODS: The published literature was surveyed using Google Scholar and PubMed entering the terms Obesity, UA, IR, Metabolic Syndrome (MetS), Gestational Diabetes (GDM), Polycystic Ovarian Syndrome (PCOS). RESULTS: UA had substantial positive relationships with IR, as well as obesity, MetS, DM, GDM, and PCOS. Evidently UA with a role in oxidative stress, endothelial dysfunction and induction of inflammation may cause IR in totality, the major factor in development of MetS and related diseases. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin based IR index, correlated positively with UA. Moreover, specifically triglyceride to high density lipoprotein cholesterol ratio (TG/HDL-C), visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride to fasting glucose (TyG) index are noninsulin-based IR indices of positive correlations with UA. MetS score for IR (MetS-IR), a non-insulin based IR index, had significantly proportional correlations with MetS components as well as UA level. UA to HDL-cholesterol ratio (UHR) was a pronounced statistical predictor of MetS and diabetes control. UA positively associated with hyperinsulinemia and IR in prediabetes. CONCLUSION: Succinctly UA can be an emerging biochemistry marker of predictive role in IR, MetS and related anomalies. More hyperuricemia related studies are warranted to be oriented from being correlational to mechanistic.

The use of complementary and alternative medicine in fertility and gynaecological disorders in Jordan: a mixed-method descriptive study

Journal of Pharmaceutical Health Services Research, Oct 14, 2022

In vitro Antiproliferative Properties of Lipophililic-Acid Chelating Fluoroquinolones and TriazoloFluoroquinolones with 7-dihaloanilinosubstitution

Anti-cancer Agents in Medicinal Chemistry, Nov 1, 2022

Background: Incidence rates and prevalence of cancer are substantially high globally. New safe th... more Background: Incidence rates and prevalence of cancer are substantially high globally. New safe therapeutic drugs are endorsed to overcome the high toxicity and poor safety profile of clinical anticancer agents. Objectives: As antineoplastic Vosaroxin is a commercial fluoroquinolone (FQ), we hypothesize that superlative antiproliferation activity of lipophilic FQs/TFQs series correlates to their acidic groups and C8-C7 ethylene diamine Chelation Bridge along with bulky dual halogenations. Methods: We tested dual lipophilic- acidic chelating FQs with a genuine potential of antiproliferative propensities based on their dual DPPH- and NO- radicals scavenging biocapacities using cell based – and colorimetric assays vs. respective reference agents as their molecular action mechanism. Results: In this work, 9 lipophilic-acid chelating FQs and their cyclized TriazoloFQs (TFQs) designed to bear 7- dihaloanilino substituents with a special focus on dichlorosubstitutions have been prepared, characterized and screened against breast T47D and MCF7, Pancreatic PANC1, colorectal HT29, cervical HELA, lung A375, skin A549, and Leukaemia K562 cancer cell lines using sulforhodamine B colorimetric bioassay. Parameters including potency, toxicity, and selectivity (potency/toxicity) have been reported along with DPPH- and NO- radicals’ scavenging propensities - as their molecular action mechanism- in comparison to ascorbic acid and indomethacin, respectively. Using Griess assay in lipopolysaccharide (LPS) prompted RAW264.7 macrophages inflammation, IC50 values (μM) in the ascending order of new FQs’ NO scavenging/antiinflammation capacity were 4a < 3a < 4c < indomethacin (23.8 <33.4 < 36 vs. indomethacin’s 124, respectively). Exceptionally unlike the rest, reduced FQ, 4b exhibited remarkably superior DPPH radical scavenging capacity to ascorbic acid (IC50 values (μM) 19.9 vs. 123.9, p < 0.001). In comparison to cisplatin; nitroFQs (3a, 3b and 3c), the reduced FQs (4a, 4b, and 4c) and the TFQs (5a, 5b and 5c) exerted substantial micromolar antiproliferation IC50 values < 50 μM in cervical Hela cancer cells but lacked comparable bioactivity in leukaemia K562. In both breast MCF7 and T47D cancer cell lines, FQs/TFQs 4a < 3a < 5b (respective IC50 values (μM) 0.52 < 22.7 < 24 vs. cisplatin’s 41.8 and 0.03 < 4.8 < 27 vs. cisplatin’s 509), and in both GI system colorectal HT29 and pancreatic PANC1 cancer cells FQs/TFQs 4a < 3a < 5b and 4a< 3a (respective IC50 values (μM) 0.12 < 3.5 < 15.9 vs. cisplatin’s 148 and 1.5 < 10.4 vs. cisplatin’s 25.5), exerted nanomolar-micromolar affinities of antiproliferation potencies < 50μM. Besides in lung A375 cancer cells FQs/TFQs 4c < 4a < 3a and in skin A549 cancer cells 5c < 3c < 4a < 3a < 4c (respective IC50 values (μM) 0.07 < 3.2 < 10.3 vs. cisplatin’s 390 and 0.5 < 2.3 < 3.8 < 8.8 < 17.3 vs. cisplatin’s 107) exhibited nanomolar-micromolar antineoplastic capacities < 50 μM. Their spectrum of selectivity indices for safety in fibroblasts PDL-based 72h incubations was reported. Unequivocally 4b reduction of viability effectiveness linked with its DPPH radical scavenging effects (without a matching antiinflammation effect). Explicitly 4a, 3a and 4c exerted exquisite antiinflammation-selective cytotoxicity duality in vitro. Conclusions: Such a new potential chelation mechanism can explain the pronounced difference in antineoplastic activity of new FQs/TFQs.

Planta Medica, Feb 23, 2011