Anti-Inflammatory and Antioxidant Effects of Rosmarinic Acid Trimetallic (Cu0.5Zn0.5Fe2O4) Nanoparticles.

Newly, green metallic-nanoparticles (NPs) have received scientists' interest due to their wide variable medicinal applications owned to their economical synthesis and biologically compatible nature. In this study, we used rosmarinic acid (RosA) to prepare Cu0.5Zn0.5FeO4 NPs and later encapsulated them using PEG polymer. Characterization of NPs was done using the XRD method and SEM imaging. Further, we explored the encapsulated NPs for anti-inflammatory properties by downregulating the expression of pro-inflammatory cytokines mRNA in LPS-stimulated Raw 264.7 cells. Besides, employing DPPH, NO and ABTS radical scavenging assays to examine the antioxidant activity of the synthesized Cu0.5Zn0.5FeO4 NPs. Cu0.5Zn0.5FeO4 NPs revealed moderate antioxidant activity by scavenging DPPH and nitric oxide. We demonstrated that the NPs showed high potential anti-inflammatory activity by suppressing the mRNA and protein levels of pro-inflammatory cytokines in a dose-dependent manner, in LPS-induced Raw 264.7 cells. To our best knowledge, this is the first report where RosA was found to be a suitable phyto source for the green synthesis of Cu0.5Zn0.5FeO4 NPs and their in vitro anti-inflammatory and antioxidant effects. Taken together, our findings suggest that the RosA is a green resource for the eco-friendly synthesis of Cu0.5Zn0.5FeO4/PEG NPs, which further can be employed as a novel anti-inflammatory therapeutic agent.

Assessing the Protective Role of Epigallocatechin Gallate (EGCG) against Water-Pipe Smoke-Induced Toxicity: A Comparative Study on Gene Expression and Histopathology.

Exposure to water-pipe smoking, whether flavored or unflavored, has been shown to instigate inflammation and oxidative stress in BALB/c mice. This consequently results in alterations in the expression of inflammatory markers and antioxidant genes. This study aimed to scrutinize the impact of Epigallocatechin gallate (EGCG)-a key active component of green tea-on inflammation and oxidative stress in BALB/c mice exposed to water-pipe smoke. The experimental setup included a control group, a flavored water-pipe smoke (FWP) group, an unflavored water-pipe smoke (UFWP) group, and EGCG-treated flavored and unflavored groups (FWP + EGCG and UFWP + EGCG). Expression levels of IL-6, IL1B, TNF-α, CAT, GPXI, MT-I, MT-II, SOD-I, SOD-II, and SOD-III were evaluated in lung, liver, and kidney tissues. Histopathological changes were also assessed. The findings revealed that the EGCG-treated groups manifested a significant decline in the expression of inflammatory markers and antioxidant genes compared to the FWP and UFWP groups. This insinuates that EGCG holds the capacity to alleviate the damaging effects of water-pipe smoke-induced inflammation and oxidative stress. Moreover, enhancements in histopathological features were observed in the EGCG-treated groups, signifying a protective effect against tissue damage induced by water-pipe smoking. These results underscore the potential of EGCG as a protective agent against the adverse effects of water-pipe smoking. By curbing inflammation and oxidative stress, EGCG may aid in the prevention or mitigation of smoking-associated diseases.

Green Synthesis of Gold, Iron and Selenium Nanoparticles Using Phytoconstituents: Preliminary Evaluation of Antioxidant and Biocompatibility Potential.

This study aimed at fabricating gold (Au), iron (Fe) and selenium (Se) nanoparticles (NPs) using various natural plant extracts from the Fertile Crescent area and evaluating their potential application as antioxidant and biocompatible agents to be used in the pharmaceutical field, especially in drug delivery. The Au-NPs were synthesized using Ephedra alata and Pistacia lentiscus extracts, whereas the Fe-NPs and Se-NPs were synthesized using peel, fruit and seed extracts of Punica granatum. The phytofabricated NPs were characterized by the UV-visible spectroscopy, scanning electron microscope, Fourier transform infrared spectroscopy, X-ray diffraction (XRD) and energy-dispersive X-ray (EDS) spectroscopy. Scanning electron microscope technique showed that the synthesized NPs surface was spherical, and the particle size analysis confirmed a particle size of 50 nm. The crystalline nature of the NPs was confirmed by the XRD analysis. All synthesized NPs were found to be biocompatible in the fibroblast and human erythroleukemic cell lines. Se-NPs showed a dose-dependent antitumor activity as evidenced from the experimental results with breast cancer (MCF-7) cells. A dose-dependent, free-radical scavenging effect of the Au-NPs and Se-NPs was observed in the DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay, with the highest effect recorded for Au-NPs.

Influence of geographic conditions on body length of male newborns in Kyrgyzstan.

Newborn length has been reported by many researchers to be reduced at high altitudes. However, many of these studies lacked adequate control of the ethnic group which may be confounding the altitude differences. In addition, few studies have examined the sources of variation in birth weight at high altitudes that may be related to ethnic group adaptation to the stresses of this hypoxic environment. In our study, we tested the hypotheses that the effect of altitude differences in newborn length depends on ethnic variation. Samples of 3359 healthy male newborns from different areas in Kyrgyzstan between the years 2003 and 2011 were analyzed for altitude and ethnic variation on male newborn length. Our results indicate significant decrease in male newborn length as a latitude increase. It is concluded that ethnic group difference in pregnancy outcome reflects a better state of adaptation to high altitude in this healthy indigenous population and that long-term genetic selection may be the most plausible explanation for these ethnic differences.

Association of Breastfeeding Duration with Susceptibility to Allergy, Influenza, and Methylation Status of TLR1 Gene.

Background and Objectives: This study aimed to investigate the possible association between exclusive breastfeeding duration during early infancy and susceptibility to allergy and influenza in adulthood. Furthermore, we also investigated the association of breastfeeding duration with DNA methylation at two sites in the promoter of the toll-like receptor-1 (TLR1) gene, as well as the association between DNA methylation of the toll-like receptor-1 (TLR1) gene and susceptibility to different diseases. Materials and Methods: Blood samples were collected from 100 adults and classified into two groups according to breastfeeding duration (<6 months and ≥6 months) during infancy. Subjects were asked to complete a questionnaire on their susceptibilities to different diseases and sign a consent form separately. Fifty-three samples underwent DNA extraction, and the DNA samples were divided into two aliquots, one of which was treated with bisulfite reagent. The promoter region of the TLR1 gene was then amplified by polymerase chain reaction (PCR) and sequenced. Results: We found a significant association between increased breastfeeding duration and a reduction in susceptibility to influenza and allergy, as well asa significant reduction in DNA methylation within the promoter of the TLR1 gene. No association was found between DNA methylation and susceptibility to different diseases. Conclusions: The findings demonstrate the significance of increased breastfeeding duration for improved health outcomes at the gene level.

Magnetic nanoparticle-based combination therapy: Synthesis and in vitro proof of concept of CrFe2O4- rosmarinic acid nanoparticles for anti-inflammatory and antioxidant therapy.

Magnetic drug delivery systems using nanoparticles present a promising opportunity for clinical treatment. This study explored the potential anti-inflammatory properties of RosA- CrFe2O4 nanoparticles. These nanoparticles were developed through rosmarinic acid (RosA) co-precipitation via a photo-mediated extraction technique. XRD, FTIR, and TEM techniques were employed to characterize the nanoparticles, and the results indicated that they had a cubic spinel ferrite (FCC) structure with an average particle size of 25nm. The anti-inflammatory and antioxidant properties of RosA- CrFe2O4 nanoparticles were evaluated by using LPS-induced raw 264.7 macrophages and a hydrogen peroxide scavenging assay, respectively. The results showed that RosA- CrFe2O4 nanoparticles had moderate DPPH scavenging effects with an IC50 value of 59.61±4.52µg/ml. Notably, these nanoparticles effectively suppressed the expression of pro-inflammatory genes (IL-1ß, TNF-α, IL-6, and iNOS) in LPS-stimulated cells. Additionally, the anti-inflammatory activity of RosA- CrFe2O4 nanoparticles was confirmed by reducing the release of secretory pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-stimulated macrophages. This investigation highlights the promising potential of Phyto-mediated CrFe2O4-RosA as an anti-inflammatory and antioxidant agent in biomedical applications.

Nanoencapsulated Curcumin Mitigates Liver Injury and Drug-Metabolizing Enzymes Induction in Diclofenac-Treated Mice.

Curcumin (CUR) is a natural product with known anti-inflammatory, antioxidant, and hepatoprotective properties. The aim of this study was to formulate CUR into a polymeric nanoparticle (NP) formulation and examine its potential hepatoprotective activity in an animal model of diclofenac (DIC)-induced hepatotoxicity. CUR was loaded into polymeric NPs composed of poly(ethylene glycol)-polycaprolactone (PEG-PCL). The optimal CUR NPs were evaluated against DIC-induced hepatotoxicity in mice, by studying the histopathological changes and gene expression of drug-metabolizing cyp450 (cyp2c29 and cyp2d9) and ugt (ugt2b1) genes in the livers of the animals. The optimal NPs were around 67 nm in diameter with more than 80% loading efficiency and sustained release. Histological findings of mice livers revealed that CUR NPs exhibited a superior hepatoprotective effect compared to free CUR, and both groups reduced DIC-mediated liver tissue injury. While treatment with DIC alone or with CUR and CUR NPs had no effect on cyp2c29 gene expression, cyp2d9 and ugt2b1 genes were upregulated in the DIC-treated group, and this effect was reversed by CUR both as a free drug and as CUR NPs. Our findings present a promising application for nanoencapsulated CUR in the treatment of nonsteroidal anti-inflammatory drugs-induced liver injury and the associated dysregulation in the expression of hepatic drug-metabolizing enzymes.

Anti­angiogenic and cytotoxic evaluation of green­synthesized Fe2ZnO4 nanoparticles against MCF­7 cell line.

The use of plants for nanoparticle (NP) synthesis, grounded in green chemistry principles, is an environmentally friendly and economically viable approach. In the present study, the leaf extract of Elaeagnus angustifolia L. was used as a biosynthetic agent to generate bimetallic zinc oxide NPs. The present study investigated the effect of ZnO NPs on anti-angiogenesis and cell migration. Various bimetallic NPs, including zinc-iron oxide and nickel-zinc oxide, underwent characterization through Fourier-transform infrared spectroscopy and X-ray Diffraction within the 25-65˚ range. Confirmation of NP formation was determined by identifying the surface plasmon resonance peak. MTT assay was used to determine the cytotoxic properties of E. angustifolia L. extracts, ZnO NPs and associated metals in MCF-7 breast cancer cells. The plant extract demonstrated antiproliferative effects at 200 µg/ml, whereas E. ang-Fe2ZnO4 NPs showed varying cytotoxic effects based on concentration. The rat aortic ring and cell migration assays illuminated anti-angiogenic attributes, with the E. ang-Fe2ZnO4 NPs blocking blood vessel development entirely at 100 µg/ml, implying profound anti-angiogenic efficacy. Therefore, E. ang-Fe2ZnO4 NPs may serve a role in antiangiogenic therapy.

Modulation of wheatgrass (Triticum aestivum Linn) toxicity against breast cancer cell lines by simulated microgravity.

This study scrutinizes the effects of simulated microgravity on the antioxidant and cytotoxic potential, along with the phytochemical content of wheatgrass (Triticum aestivum Linn). To imitate microgravity, wheatgrass seeds were germinated in a 3D-clinostat at different rotations per minute (5, 10, 15, and 20 rpm), together with terrestrial gravity control, over 10 days. After germination, the methanolic extracts were analyzed using UPLC-Triple Quad LCMS for their phytochemical composition and tested for their hydrogen peroxide, nitric oxide, and DPPH scavenging activities. The cytotoxic effects of these extracts were evaluated against normal skin fibroblasts, normal breast cells (MCF-10), and breast cancer cells (MCF-7 and MDA-231). The findings showed an extended root growth in wheatgrass germinated under microgravity (WGM) compared to under gravity (WGG). Additionally, WGM extracts demonstrated increased H2O2-, NO-, and DPPH-scavenging activities and a higher content of polyphenols and flavonoids than WGG extracts. These effects were amplified with an increase in clinostat rotations. Moreover, WGM extracts were found to contain a unique set of bioactive compounds (compounds that were detected in the microgravity-germinated wheatgrass but were either absent or present in lower concentrations in wheatgrass germinated under standard gravity conditions.), including pyridoxine, apigenin, and tocopherol, among others, which were absent in WGG. The UPLC-Triple Quad LCMS analysis revealed these unique bioactive compounds in WGM. Notably, WGM extracts showed enhanced cytotoxic effects against normal skin fibroblasts, normal MCF-10, MCF-7, and breast cancer MDA-231 cell lines, with increased cytotoxicity correlating with the number of clinostat rotations. Particularly, WGM extract (at 20 rpm) demonstrated significantly stronger cytotoxicity against MCF-7 breast cancer cells. Further in-depth gene expression analysis of MCF-7 cells exposed to WGM revealed a significant downregulation of genes integral to breast cancer pathways, tyrosine kinase signaling, and DNA repair, complemented by upregulation of certain cell survival and cytotoxic genes. These alterations in genetic pathways associated with cell survival, hormone responses, and cancer progression may elucidate the enhanced cytotoxicity observed in WGM extracts. Our findings underscore the potential of microgravity as a tool to enhance the cytotoxic capabilities of wheatgrass against cancer cell lines, presenting a promising direction for future research in the field of space biology and its implications for terrestrial health.

Effects of intermittent fasting on the histology and mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice.

Introduction:There is a variation in drug response among patients who practice intermittent fasting. Alteration in the expression of drug-metabolizing enzymes (DMEs) can affect the pharmacokinetics and drug response.Aims: This research aimed to determine the effect of intermittent fasting on the mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice.Methods: Thirty-two male Balb/c mice were divided into four groups; control, nonfasting diabetic, non-diabetic fasting, and diabetic fasting mice. Insulin-dependent diabetes was induced in mice by a single high-dose (250 mg/kg) streptozocin. Mice of non-diabetic and diabetic fasting groups were subjected to 10-day intermittent fasting for 17 hours daily. Then, the mRNA expression of mouse phase I DMEs cyp1a1, cyp2c29, cyp2d9, and cyp3a11 was analyzed using real-time polymerase chain reaction. In addition, the liver of mice in all groups was examined for pathohistological alterations.Results: Diabetes downregulated the mRNA expression of hepatic drug-metabolizing cyp450s in diabetic mice, while intermittent fasting significantly (P < 0.05) increased it. Also, cyp2d9 and cyp3a11 were upregulated in the liver of diabetic fasting mice. These alterations in the gene expression were correlated with the pathohistological alterations, where livers of diabetic mice showed dilatation in the blood sinusoids and inflammatory cells leukocyte infiltrations. Whereas livers of diabetic fasting mice showed almost comparable histological findings to control mice.Conclusions: Intermittent fasting can protect the liver against diabetes-induced hepatotoxicity and the down-regulation of DME genes in the diabetic liver. These results can explain, at least partly, the inter-individual variation in the drug response during practicing fasting.

The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats.

BACKGROUND: Oxandrolone is a synthetic testosterone analog that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. AIM: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. METHODS: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. RESULTS: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest, which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P-value < 0.05). CONCLUSION: Metformin administration provided protection against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.

Analgesics Induce Alterations in the Expression of SARS-CoV-2 Entry and Arachidonic-Acid-Metabolizing Genes in the Mouse Lungs.

Paracetamol and nonsteroidal anti-inflammatory drugs are widely used in the management of respiratory viral infections. This study aimed to determine the effects of the most commonly used analgesics (paracetamol, ibuprofen, and diclofenac) on the mRNA expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and arachidonic-acid-metabolizing genes in mouse lungs. A total of twenty eight Balb/c mice were divided into four groups and treated separately with vehicle, paracetamol, ibuprofen, and diclofenac in clinically equivalent doses for 14 days. Then, the expressions of SARS-CoV-2 entry, ACE2, TMPRSS2, and Ctsl genes, in addition to the arachidonic-acid-metabolizing cyp450, cox, and alox genes, were analyzed using real-time PCR. Paracetamol increased the expressions of TMPRSS2 and Ctsl genes by 8.5 and 5.6 folds, respectively, while ibuprofen and diclofenac significantly decreased the expression of the ACE2 gene by more than 2.5 folds. In addition, all tested drugs downregulated (p < 0.05) cox2 gene expression, and paracetamol reduced the mRNA levels of cyp4a12 and 2j5. These molecular alterations in diclofenac and ibuprofen were associated with pathohistological alterations, where both analgesics induced the infiltration of inflammatory cells and airway wall thickening. It is concluded that analgesics such as paracetamol, ibuprofen, and diclofenac alter the expression of SARS-CoV-2 entry and arachidonic-acid-metabolizing genes in mouse lungs.

Reported Adverse Effects and Attitudes among Arab Populations Following COVID-19 Vaccination: A Large-Scale Multinational Study Implementing Machine Learning Tools in Predicting Post-Vaccination Adverse Effects Based on Predisposing Factors.

Background: The unprecedented global spread of coronavirus disease 2019 (COVID-19) has imposed huge challenges on the healthcare facilities, and impacted every aspect of life. This has led to the development of several vaccines against COVID-19 within one year. This study aimed to assess the attitudes and the side effects among Arab communities after receiving a COVID-19 vaccine and use of machine learning (ML) tools to predict post-vaccination side effects based on predisposing factors. Methods: An online-based multinational survey was carried out via social media platforms from 14 June to 31 August 2021, targeting individuals who received at least one dose of a COVID-19 vaccine from 22 Arab countries. Descriptive statistics, correlation, and chi-square tests were used to analyze the data. Moreover, extensive ML tools were utilized to predict 30 post vaccination adverse effects and their severity based on 15 predisposing factors. The importance of distinct predisposing factors in predicting particular side effects was determined using global feature importance employing gradient boost as AutoML. Results: A total of 10,064 participants from 19 Arab countries were included in this study. Around 56% were female and 59% were aged from 20 to 39 years old. A high rate of vaccine hesitancy (51%) was reported among participants. Almost 88% of the participants were vaccinated with one of three COVID-19 vaccines, including Pfizer-BioNTech (52.8%), AstraZeneca (20.7%), and Sinopharm (14.2%). About 72% of participants experienced post-vaccination side effects. This study reports statistically significant associations (p < 0.01) between various predisposing factors and post-vaccinations side effects. In terms of predicting post-vaccination side effects, gradient boost, random forest, and XGBoost outperformed other ML methods. The most important predisposing factors for predicting certain side effects (i.e., tiredness, fever, headache, injection site pain and swelling, myalgia, and sleepiness and laziness) were revealed to be the number of doses, gender, type of vaccine, age, and hesitancy to receive a COVID-19 vaccine. Conclusions: The reported side effects following COVID-19 vaccination among Arab populations are usually non-life-threatening; flu-like symptoms and injection site pain. Certain predisposing factors have greater weight and importance as input data in predicting post-vaccination side effects. Based on the most significant input data, ML can also be used to predict these side effects; people with certain predicted side effects may require additional medical attention, or possibly hospitalization.

In vitro anti-inflammatory and antioxidant activities of ZnFe2 O4 and CrFe2 O4 nanoparticles synthesized using Boswellia carteri resin.

The development of plant-based nano-materials is considered an eco-friendly technology because it does not involve hazardous chemicals. In this study, bimetallic ZnFe2 O4 and CrFe2 O4 nanoparticles were synthesized using an aqueous extract of Boswellia carteri resin. Synthesized ZnFe2 O4 and CrFe2 O4 nanoparticles were characterized by UV-Vis spectroscopy, FTIR, XRD, and HR-TEM. The anti-inflammatory activity was investigated in LPS-stimulated RAW 264.7 macrophages, whereas antioxidant activity was examined using a Hydrogen Peroxide Scavenging Activity Assay, Nitric Oxide Scavenging Activity Assay, and ABTS Radical Scavenging Assay. ZnFe2 O4 and CrFe2 O4 nanoparticles demonstrated a moderate scavenger of H2 O2 with IC50 values; 87.528 ± 8 µg/ml and 146.4468 ± 12 µg/ml, respectively. While they exhibited a strong scavenger of NO with IC50 values; 4.01 ± 0.7 µg/ml and 4.01 ± 0.7µg/ml, respectively. Interestingly, ZnFe2 O4 and CrFe2 O4 nanoparticles revealed an excellent anti-inflammatory activity by dose-dependently suppressing mRNA expressions of IL-1b, IL-6, and TNF-α. Also, ZnFe2 O4 and CrFe2 O4 nanoparticles suppress the protein expression of TNF-α. Together, our results proved that phyto-mediated ZnFe2 O4 and CrFe2 O4 nanoparticles using Boswellia carteri resin have great potential in biomedical applications such as anti-inflammatory and antioxidant. PRACTICAL APPLICATIONS: Our phyto-synthesized chromium iron oxide bimetallic nanoparticles (NPs) have shown a novel and potent anti-inflammatory activity, with remarkable biosafety toward tested macrophages. Zinc iron oxide bimetallic NPs exhibited anti-inflammatory effect with a lesser extent compared to the former, with moderate cytotoxicity against tested macrophages. Both zinc and chromium iron oxide NPs exhibited an equivalent antioxidant activity. Our resin-capped chromium iron oxide NPs are suggested to be a competing nonsteroidal anti-inflammatory agent; it is further recommended to establish advanced animal studies to confirm their biosafety, stability, and anti-inflammatory activity accompanied with the antioxidant activity.

Ononis natrix L. Lowers the Blood Glucose Concentration in Wistar Rats with Streptozotocin-induced Diabetes Mellitus.

BACKGROUND: Practitioners of traditional medicine use the decoction of Ononis natrix L. to treat hyperglycemia. The literature offers no evidence to support the use. OBJECTIVE: To investigate the effect of the decoction of Ononis natrix L. on the blood glucose concentration in Wistar rats (Rattus norvegicus) with streptozotocin-induced diabetes mellitus. METHODS: We obtained 35 Wistar rats from the animal colony of The University of Jordan School of Medicine. We induced diabetes by a single intraperitoneal injection of streptozotocin (60 mg/kg body weight) and 23 rats (66%) survived to allocation. We randomly assigned the rats to one of four groups: negative control (1% Tween 80 in distilled water), positive control (100 mg/kg metformin), high-dose treatment (7.5 mL of the decoction), and low-dose treatment (3.5 mL of the decoction). We administered the doses twice daily by oral gavage for two weeks and measured the tailblood glucose concentration twice daily, once before the first dose and another time after the second dose. We used linear mixed-effects regression to model the change in blood glucose concentration as a function of the experimentation groups, with adjustments for pseudoreplication and temporal variation. RESULTS: The estimated mean change was 1 mmol/L (-30 to 31 mmol/L) for the negative control group, -26 mmol/L (-56 to 5 mmol/L) for the positive control group, -75 mmol/L (-108 to -42) for the low-dose treatment group, and -82 mmol/L (-111 to -53 mmol/L) for the high-dose treatment group. CONCLUSION: In conclusion, we demonstrate, for the first time, the hypoglycemic effect of Ononis natrix L. in an animal model of diabetes.

Association of KDR rs1870377 genotype with clopidogrel resistance in patients with post percutaneous coronary intervention.

BACKGROUND: Clopidogrel is an antiplatelet therapy that is widely used in pre and post percutaneous (PCI) coronary intervention procedures to prevent platelet aggregation and stent restenosis. However, there is a wide inter-individual variation in clopidogrel response and some patients showed resistance against the activity of Clopidogrel. Kinase insert domain receptor (KDR) gene is responsible for the transcription of vascular endothelial growth factor receptor 2 (VEGFR2) that plays a major role in the cardiovascular diseases (CVDs) and platelet aggregation. The aim of this study was to find out the association of KDR rs1870377 genotype with clopidogrel resistance (CR) in CVD patients, of Iraqi Arabic origin, hospitalized for elective PCI. MATERIALS AND METHODS: This study was a case-control study with a total of 324 PCI patients. Those patients were classified into 213 patients with non-clopidogrel resistant and 111 patients with CR, depending on the analysis of platelet activity phenotype after clopidogrel administration. KDR rs1870377 was genotyped for all patients using polymerase chain reaction-restriction fragment length polymorphism technique and confirmed by DNA Sänger sequencing through applying Biosystems Model (ABI3730x1). RESULTS: KDR rs1870377 SNP is strongly associated (Chi-sqaure, p vale <0.05) with CR under dominant, co-dominant and recessive models. Additionally, A allele in the rs1870377 SNP may have an impact on the serum levels of VEGFR2 and low density lipoprotein. CONCLUSIONS: KDR rs1870377 SNP is a potential genetic biomarker of CR among CVD patients of Iraqi Arabic origin. Further clinical studies, with larger sample, are required to confirm the findings of this study.

Investigation of ACE rs4646994, MTHFR rs1801133 and VDR rs2228570 Genotypes in Jordanian Patients with Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic disease characterized by widespread body pain, weakness in certain parts of the body (critical points), low pain tolerance, sleep disturbances, and fatigue. This syndrome is considered rare in Jordan. OBJECTIVES: The research aimed to find out the association of the angiotensin converting enzyme, methylenetetrahydrofolate reductase, and vitamin D receptor (ACE, MHFTR, and VDR, respectively) genotypes with FMS among Jordanian patients. METHODS: This work included 22 FM patients and 22 healthy individuals of Jordanian Arabic origin. The ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 genotypes were determined using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism. RESULTS: No associations between ACE rs4646994, MTHFR rs1801133, and VDR rs2228570 with the vulnerability of a person for the development of FMS were found. However, we found an association between the ACE rs4646994 genotype and restless leg among FM patients. CONCLUSION: Based on the result from this study, it appears that the ACE rs4646994 genotype is associated with restless leg among FMS patients of Jordanian origin. Further clinical investigations with larger sample sizes are required to confirm these findings and understand the molecular mechanism of ACE rs4646994 genetic variant in the restless leg syndrome among FM patients.

Investigating the association of CD36 gene polymorphisms (rs1761667 and rs1527483) with T2DM and dyslipidemia: Statistical analysis, machine learning based prediction, and meta-analysis.

CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.

Effect of simulated microgravity on the antidiabetic properties of wheatgrass (Triticum aestivum) in streptozotocin-induced diabetic rats.

Microgravity affects plant growth and content. A three-dimensional clinostat was used at 4 rotations/min to rotate the seeds of Triticum aestivum cultivar (Ammon) in three dimensions for 7 days, following which the antioxidant activities of ethanolic extracts were evaluated using both nitric oxide- and hydrogen peroxide-scavenging activities. The antidiabetic activities of ethanolic extracts were evaluated by measuring the concentration of plasma glucose, insulin, C peptide, and glycated hemoglobin (HbA1c); determining the number of ß cells in the pancreatic islets; and performing the glucose tolerance test. Furthermore, the effects of the ethanolic extracts on the lipid profile and liver function were estimated. After rats were sacrificed, their pancreases were isolated and used for histopathological processing. The results indicated that the antioxidant potential and antioxidant metabolite content were significantly increased under microgravity conditions in comparison to those under normal gravity conditions. Rats treated with an extract of wheatgrass (T. aestivum) germinated over a period of 6-10 days under microgravity (WGM) showed a significant reduction in the levels of serum glucose, HbA1C, urea, creatinine, aspartate aminotransferase and alanine aminotransferase, and insulin resistance compared to rats treated with an extract of wheatgrass germinated under gravity. Additionally, the total cholesterol and low-density lipoprotein cholesterol levels were significantly decreased. In contrast, high-density lipoprotein cholesterol, C-peptide, and insulin levels rose significantly after treatment with T. aestivum germinated under microgravity. WGM is a promising potential diabetic treatment without side effects with a low manufacturing cost.

Arg399Gln XRCC1 Polymorphism and Risk of Squamous Cell Carcinoma of the Head and Neck in Jordanian Patients.

BACKGROUND AND OBJECTIVE: X-ray repair cross-complementing group1 (XRCC1) is a key protein in base excision repair and closely associated with the coordination of the base excision repair pathway. Many studies have focused on XRCC1 SNPs and have shown an associated between these SNPs and the risk of several types of cancers, including head and neck cancer. There are many single nucleotide polymorphisms XRCC1 gene (SNPs) and the most common SNP that result in amino acid substitutions is exon 10 (Arg399Gln). This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. MATERIAL AND METHOD: Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models, namely co-dominant, dominant, and recessive genotypes. Arg/Arg homozygous major genotype was significantly (p value <0.05) associated with head and neck squamous cell carcinoma incidence with odd ratio of 2.23 and 2.24 for the co-dominant and recessive models, respectively. CONCLUSION: The findings indicated that Arg399Gln allele was associated with squamous cell carcinoma of the head and neck among Jordanian patients. This allele might be used as a genetic biomarker of squamous cell carcinoma of the head and neck.