Molecular mechanism of anandamide-induced apoptosis in non-melanoma skin cancer.

Non-melanoma skin cancer (NMSC) is the most common cancer in the United States. The absence of selective toxicity is the major problem associated with chemotherapeutic and radiation therapy for NMSCs. The goal of the present study was to determine the molecular mechanism of action of a potential selective treatment for NMSC, arachidonoyl ethanolamide [AEA, (also known as anandamide)]. Our research revealed that two factors provide AEA with its selective toxicity, the elevated cyclooxygenase-2 (COX-2) levels and the activated endoplasmic reticulum (ER) stress signaling in tumorigenic keratinocytes which differentiates them from normal cells. COX-2 is an enzyme that promotes tumor development by synthesizing E-series prostaglandins (PGs) that promote cell proliferation. Selective inhibition of COX-2 is successfully used in treatment of skin cancer. Rather than inhibiting COX-2, the novel approach of exploiting the overexpression of COX-2 was utilized. In tumorigenic keratinocytes, AEA was metabolized by COX-2 to cytotoxic J-series prostaglandin-ethanolamides (PGJ2-EAs) that are structurally distinct from arachidonic acid (AA)-derived J-series PGs. This data is novel and to the candidate's knowledge, this is the first report showing that PGJ2-EAs are produced as an AEA metabolic product. Furthermore, several studies showed that J-series PGs derived from AA induce oxidative stress, ER stress and apoptosis. Therefore, the candidate hypothesized that AEA is metabolized to PGJ2-EAs, which induce oxidative stress followed by ER stress and ultimately apoptosis as a novel mechanism of action of AEA. The candidate also took advantage of evidence, which shows that ER stress is moderately elevated in tumor cells when compared to normal cells. Under these circumstances, the exposure of cells to agents that induce additional stress is expected to cause overwhelming ER stress and subsequently apoptosis selectively in tumor cells. Indeed, the candidate determined that AEA induced ER stress-mediated apoptosis in COX-2 expressing tumor cells but not in normal cells. Hence, the present study provides an alternative strategy for topical treatment of NMSCs that will be selectively cytotoxic to cancer cells but not detrimental to normal, healthy surrounding cells.Ph.D

Calli Essential Oils Synergize with Lawsone against Multidrug Resistant Pathogens.

The fast development of multi-drug resistant (MDR) organisms increasingly threatens global health and well-being. Plant natural products have been known for centuries as alternative medicines that can possess pharmacological characteristics, including antimicrobial activities. The antimicrobial activities of essential oil (Calli oil) extracted from the Calligonum comosum plant by hydro-steam distillation was tested either alone or when combined with lawsone, a henna plant naphthoquinone, against MDR microbes. Lawsone showed significant antimicrobial activities against MDR pathogens in the range of 200-300 µg/mL. Furthermore, Calli oil showed significant antimicrobial activities against MDR bacteria in the range of 180-200 µg/mL, Candida at 220-240 µg/mL and spore-forming Rhizopus fungus at 250 µg/mL. Calli oil's inhibition effect on Rhizopus, the major cause of the lethal infection mucormycosis, stands for 72 h, followed by an extended irreversible white sporulation effect. The combination of Calli oil with lawsone enhanced the antimicrobial activities of each individual alone by at least three-fold, while incorporation of both natural products in a liposome reduced their toxicity by four- to eight-fold, while maintaining the augmented efficacy of the combination treatment. We map the antimicrobial activity of Calli oil to its major component, a benzaldehyde derivative. The findings from this study demonstrate that formulations containing essential oils have the potential in the future to overcome antimicrobial resistance

Uloga kompleksa germanija s L-cysteinom i α-tokoferolom kao stimulatora antioksidativnog obrambenog sustava štakora izloženih gama-zračenju

This study was conducted to evaluate the potency of the newly prepared germanium L-cysteine α-tocopherol complex [germanium dichloro tetrakis (L-cysteinyl-α-tocopherol amide) dichloride] as a protective agent against γ-irradiation-induced free radicals production and liver toxicity. Male Swiss albino rats were injected intraperitoneally with the germanium complex in a concentration of 75 mg kg-1 body mass per dose, for 6 successive doses, last dose administered twenty minutes pre-exposure to a single dose of whole body γ-irradiation of 6.5 Gy. Lipid peroxidation (LPx), nitric oxide (NO), glutathione (GSH) levels, and activity of the antioxidant enzymes glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were estimated in blood and liver, and blood total protein, cholesterol, triglyceride and α-tocopherol content were estimated as well. The results revealed that administration of germanium complex pre-irradiation resulted in significant (p < 0.001) improvement compared to the irradiated group in the level of hepatic and blood LPx. Hepatic GSH revealed a significant increase (p < 0.001), while its level showed no significant variation in blood. Also, the level of NO in blood and liver increased significantly (p < 0.001). On the other hand, pretreatment with the germanium complex normalized the activities of SOD, GPx and CAT in blood and liver when compared to the irradiated group. The study also documents a marked decrease in the blood triglyceride and cholesterol (p < 0.001); and significant increase (p < 0.001) of -tocopherol and total protein contents in blood. These biochemical changes were associated with marked improvement of histological status. Therefore, the germanium L-cysteine α-tocopherol complex may be a good candidate for ameliorating the changes induced by irradiation, which indicates the beneficial radio-protective role of this antioxidant agent.U radu je procjenjivan kompleks germanija s L-cisteinom i α-tokoferolom [germanijev diklortetrakis (L-cisteinil-α-tokoferol amid) diklorid] kao zaštitno sredstvo protiv slobodnih radikala induciranih γ-zračenjem hepatotoksičnosti. Mužjacima švicarskih albino štakora davan je intraperitonealno kompleks germanija, u 6 sukcesivnih doza po 75 mg kg-1 tjelesne mase, posljednja doza dana je dvadeset minuta prije izlaganja cijelog organizma jednokratnoj dozi γ-ozračivanja od 6,5 Gy. U krvi i jetri praćena je razina lipidne peroksidacije (LPx), dušikovog(II) oksida (NO), glutationa (GSH), aktivnost antioksidativnih enzima glutation peroksidaze (GPx), superoksid dismutaze (SOD) i katalaze (CAT), te količina ukupnih proteina u krvi, kolesterola, triglicerida i α-tokoferola. Rezultati su pokazali da je primjena germanijevog kompleksa značajno (p < 0,001) poboljšala koncentraciju jetrenih i krvnih LPx. Koncentracija GSH u jetri je značajno porasla (p < 0,001), dok se njegova razina u krvi nije značajno promijenila. Koncentracija NO u krvi i jetri značajno se smanjila (p < 0,001). S druge strane, prethodna obrada s kompleksom germanija normalizirala je aktivnost SOD, GPx i CAT u krvi i jetri u odnosu na ozračenu skupinu. Istraživanja su također pokazala značajno smanjenje triglicerida i kolesterola (p < 0,001) i značajno povećanje (p < 0,001) alfa-tokoferola i ukupnih proteina u krvi. Te biokemijske promjene su povezane s izraženim poboljšanjem histoloških promjena u odnosu na ozračenu skupinu. Opisani kompleks germanija mogao bi se kao antioksidativno sredstvo potencijalno upotrijebiti za spriječavanje promjena uzrokovanih zračenjem

Association of IL-23R gene single nucleotide polymorphism; rs 11209026 with incidence and severity of ankylosing spondylitis in a cohort of Egyptian patients

The aim of the present study was to investigate the possible association between incidence and severity of ankylosing spondylitis (AS) in a cohort of Egyptians and Interleukin-23Receptor (IL23R) genesingle nucleotide polymorphism(rs11209026).Methods: The study included thirty-two AS patients and forty volunteers who serves as a control group. The studied polymorphismwas genotyped using 50 Nuclease assay.Results: A statistically significant difference was detected between both studied groups as regards different IL23R genesingle nucleotide polymorphism (rs11209026) genotypes. Heterozygous genotype was the most prevailing among both cases and controls. At a cutoff level of 110 pg/mL, a statically significant difference was observed between cases and controls as regards serum IL23 level.Conclusions: In Egyptians, IL-23R single nucleotide polymorphism (rs11209026) appears to be associated with ankylosing spondylitis occurrence not severity, while higher levels of IL-23 might be associated with disease severity.Keywords: Interleukin 23 receptor, Polymorphism, rs 11209026, Ankylosing spondyliti

CHEMICAL AND BIOLOGICAL ANALYSIS OF THE BIOCTIVE FRACTIONS OF THE LEAVES OF SCAEVOLA TACCADA (GAERTN.) ROXB

Objective: Scaevola taccada. (Gaertn.) Roxb. is widely dispersed all along the coasts of Africa. It is used in folk medicine for diversity of ailments. This study aims to investigate the major phytoconstituents and biological activities of the leaves of S. taccada (Gaertn.) Roxb. Methods: In vitro biological examination viz. antimicrobial, cytotoxic and antioxidant activities of the ethanol extract of the leaves (EE) and its fractions; (petroleum ether (PE), methylene chloride (MC), ethyl acetate (EA) and n-butanol(BuOH)) were carried out. Estimation of the phytochemicals of biologically active fractions was done. Results: n-butanol fraction displayed remarkable antimycobacterium activity. Petroleum ether as well as n-butanol fractions evidenced a cytotoxic effect on breast carcinoma cell line (MCF7) and colon carcinoma cell line (HCT) with IC50 11.7 and 15.04 µg/ml respectively. Moreover, ethyl acetate fraction exhibits an antioxidant effect with EC50 476.7±0.57 µg/ml. n-tetradecane 1, α-amyrin palmitate 2, α-amyrin acetate 3, α-amyrin 4, stigmasterol 5, luteolin-7-O-β-glucoside 6, rutin 7 and alidyjosioside 8 were identified in S. taccada (Gaertn.) Roxb. leaves. Conclusion: Petroleum ether fraction is a cytotoxic candidate, especially against (MCF-7). It exhibited a moderate antifungal and antibacterial against certain Gram-positive bacteria. Ethyl acetate showed an antioxidant effect along with moderate antifungal activity. n-butanol fraction exerted potential antimycobacterial, significant cytotoxic activity against (HCT), good antifungal and antibacterial against Gram-positive and Gram-negative bacteria. Stigmasterol, luteolin-7-O-β-glucoside, rutin and alidyjosioside were isolated for the first time from S. taccada (Gaertn.) Roxb. Leaves

2-(Morpholin-4-yl)-6-(1H-pyrrol-1-yl)­pyridine-3,5-dicarbonitrile

In the title compound, C15H13N5O, the morpholine ring adopts a chair conformation. The dihedral angle between the pyrrole ring and the pyridine ring is 28.93 (14)°. In the crystal, the molecules are linked by C—H⋯O hydrogen bonds occur, and aromatic weak π–π stacking [centroid–centroid separation = 4.178 (2) Å] and C—H⋯π inter­actions consolidate the packing

Correlation between Ultrasound Findings and Molecular Subtypes of Breast Cancer

Breast cancer is the most common malignant tumor and the major cause of death among women worldwide. Molecular subtyping of breast cancer is important to individualize its management, to understand prognosis of disease and avoid overtreatment. The current study aimed at correlating the breast cancer subtypes with their different ultrasound criteria. The ultrasound findings might have an important role in predicting different groups. The current study is a retrospective study. Which was conducted on 40 females patients with breast cancer; during the period from November 2020 till March 2021.The age were 45–65 years old. They were presented to the Radiology Department, ·Ain-Shams University, Faculty of Medicine. The selected cases had been afforded from: the Breast-unit of General Surgery Hospital, El Demerdash University Hospital, Clinical Oncology & Nuclear Medicine Department. When analyzing the main four breast cancer subtypes in the current work we found that the rates of Luminal A was 34%, Luminal B was 40%, HER2 was 15%, and TNBC was 11%. LA subtype was strongly associated with hypoechoic lesions showing irregular shape, speculated margin surrounded by desmoplastic reaction with posterior shadowing. LB subtype was associated with irregular shape and speculated margin with absence of desmoplastic reaction. Human Epidermal Growth Factor (HER2) subtype in the current study was found to be associated with irregular shape, lobulated margin, absent desmoplastic reaction with posterior acoustic mixed shadowing and enhancement. This could be related to suspicious microcalcifications. Triple Negative Breast Cancer (TNBC) lesions in the present work were predominantly oval in shape with• circumscribed margin; the benign looking malignant lesions which carry the worst prognosis. Based on the latter finding, the good radiologist should be aware about ultround features of different molecular subtype in order not to under diagnose a malignant breast lesion. The sonographic features as margin, shape, posterior acoustic features were significantly associated with molecular subtypes. The histopathological grade and hormone receptor status. Being able to predict the molecular subtype. The current study recommend that the radiologist should be aware about different imaging features of different molecular subtypes especially the triple negative breast cancer which had the most benign looking criteria aiming for better lesion characterization and to allow the patient to benefit from earlier non-invasive, cheap diagnosis and the curable on time treatment

Synthesis and reactions of (Z)-2-imino-5-(3,4,5-trimethoxy benzylidene)thiazolidin-4(H)one

5-Arylmethylene-2-imino-4-oxo-2-thiazolidine 3 was obtained as the sole product from the reaction of α-cyano-3,4,5-trimethoxy cinnamonitrile and/or ethyl-α-cyano-3,4,5-trimethoxy cinnamate (1a,b) with 2-imino-4-oxo-2-thiazolidine 2. The reaction of 3 with benzyl amine gave the imidazolidin-4(H)one derivative 4 while with hydrazine hydrate afforded the dimeric product 5. Also, reaction of thiazolidinone derivative 3 with piperidine gave thiazol-4(5H)one derivative 6 which on treatment with Grignard reagent and active methylene compounds afforded thiazolidin-4-one derivatives 7-9, respectively. Compound 6 was converted to the potassium salt 10 which treated with acetic acid, ethyl chloroacetate and furoyl chloride to give the compounds 11-13, respectively. The structures of all new compounds were evidenced by microanalytical data and spectral data