Dermatological Lesions of Cholesterol Embolization Syndrome and Kaposi Sarcoma Mimic Primary Systemic Vasculitis: Case Report Study

Primary systemic vasculitis can present with a wide spectrum of manifestations ranging from systemic non-specific features such as fever, malaise, arthralgia, and myalgia to specific organ damage. We describe two cases of cholesterol embolization syndrome and Kaposi sarcoma mimicking primary systemic vasculitis, both of which were characterized by features such as livedo reticularis, blue toe syndrome, a brown, purpuric skin rash, and positive p-ANCA associated with Kaposi sarcoma. Establishing the right diagnosis was challenging, and thus we aim in this study to highlight the possible ways to distinguish them from primary systemic vasculitis. Keywords: Dermatological lesions, Cholesterol embolization syndrome, Kaposi sarcoma, vasculitis mimic

Design, synthesis, docking and mechanistic studies of new thiazolyl/thiazolidinylpyrimidine-2,4-dione antiproliferative agents

In this article, we display on the synthesis and biological evaluation of a new series of thiazolylpyrimidine 3a-l and thiazolidinylpyrimidine derivatives 5a-e. The structures of the new compounds were confirmed by using different spectral techniques including NMR, IR, mass spectroscopy in addition to elemental analyses. The cell viability of the new compounds was assessed against normal human mammary gland epithelial (MCF-10A) cell line. Data revealed that none of the compounds examined exhibited cytotoxic effects, and the cell viability for the compounds examined at 50 µM was greater than 87%. The antiproliferative activity of 3a-l and 5a-e was evaluated against four human cancer cell lines where the compounds showed promising activity. The most potent derivatives were compounds 3a, 3c, 3f, 3i, and 5b with GI$_{50}$ values ranging from 0.90 µM to 1.70 µM against the four cancer cell lines in comparison to doxorubicin (GI$_{50}$ = 1.10 µM). Compounds 3a, 3c and 3i showed potent antiproliferative activity with dual inhibitory action against EGFR and BRAF$^{V600E}$. Compounds 3a, 3c, and 3i demonstrated promising AutoDock scores towards EGFR and BRAF$^{V600E}$ with values of − 9.1 and − 8.6, −9.0 and − 8.5, and − 8.4 and − 8.0 kcal/mol, respectively. The physicochemical and pharmacokinetic characteristics of 3a, 3c, and 3i were anticipated, demonstrating their oral bioavailability

STATISTICAL DATA ANALYSIS WHICH RESULT FROM THE BIO-DIAGNOSIS AND BIO-TREATMENT OF INJURED RATS WITH THE HYPERLIPIDEMIA AND HYPERGLYCEMIA DISEASES

ABSTRACTObjective: This study in bioinformatics aims to investigate the potential effect of Ipomoea tricolor and Sophora tomentosa on liver function enzymesactivity, serum lipid profile, oxidative stress biomarkers, and on blood glucose in high fat diet-induced hypercholesterolemia (HC) and STZ-inducedhyperglycemia (HG) in rats.Methods: Blood glucose level, liver function enzymes, alanine aminotransferases and aspartate aminotransferases, alkaline phosphatase, and lactatedehydrogenase (LDH) were determined. Besides, lipid profile including total cholesterol (TC), triacylglycerol (TG), total lipid, and high-densitylipoprotein-cholesterol was investigated. Moreover, oxidative stress biomarkers, lipid peroxide, and nitric oxide as well as non-enzymatic antioxidant,glutathione (GSH) were also examined in different therapeutic groups.Results: A significant increase in blood glucose level, liver function enzyme activities, LDH, lipid profile and oxidative stress markers, while significantdecrease in LDH-C and GSH level in HC-HG induced rats compared to control one. A marked amelioration in all biochemical parameters underinvestigation on treatment of HC-HG rats with I. tricolor and S. tomentosa with different fluctuating percentages of improvement. Histopathologicalexamination of liver and pancreas was also performed and declared HC-HG showed congestion in portal vessels and sinusoids with mild centrilobularhepatocyte degeneration, marked hepatocyte ballooning and hydropic degeneration, while HC-HG treated rats with I. tricolor and S. tomentosa showednormal lobular hepatic architecture with mild sinusoidal dilatation and congestion. On the other hand, a histological organization of pancreas of HC-HGrats showing disarrangement changes in pancreatic blood vessels and interlobular duct as well as disordered in acini. The treatment of HC-HG rats withI. tricolor and S. tomentosa showed enhancement in Langerhans cells and restore of most pancreatic tissue in comparison with standard drugs.Conclusion: The statistical results showed that each extract ameliorated high blood glucose level liver injury, HC and oxidative stress indicatingrelieving of oxidative damage associated with the complexity of HG and HC. These results demonstrated that these two plants extracts may be acandidate intelligent antioxidant, hypolipidemic, hypoglycemic, and hepatoprotective nutraceuticals which need further clinical investigation to beapplied effectively to reduce perturbation in HC associated diabetes.Keywords: Ipomoea tricolor, Sophora tomentosa, Lipid profile and liver function enzymes, Endothelial dysfunction markers, Statistics and imagerecognition, Histopathological analysis

Design and synthesis of new thiazolidinone/uracil derivatives as antiproliferative agents targeting EGFR and/or BRAFV600E^{V600E}

Thiourea derivatives of uracil were efficiently synthesized via the reaction of 5-aminouracil with isothiocyanates. Then, we prepared uracil-containing thiazoles via condensation of thioureas with diethyl/dimethyl acetylenedicarboxylates. The structures of the products were confirmed by a combination of spectral techniques including infra-red (IR), nuclear magnetic resonance (NMR), mass spectrometry (MS) and elemental analyses. A rationale for the formation of the products is presented. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against four cancer cell lines. The compounds tested showed promising antiproliferative activity, with GI$_{50}$ values ranging from 1.10 µM to 10.00 µM. Compounds 3c, 5b, 5c, 5h, 5i, and 5j were the most potent derivatives, with GI$_{50}$ values ranging from 1.10 µM to 1.80 µM. Compound 5b showed potent inhibitory activity against EGFR and BRAF$^{V600E}$ with IC$_{50}$ of 91 ± 07 and 93 ± 08 nM, respectively, indicating that this compound could serve as a dual inhibitor of EGFR and BRAF$^{V600E}$ with promising antiproliferative properties. Docking computations revealed the great potency of compounds 5b and 5j towards EGFR and BRAF$^{V600E}$ with docking scores of −8.3 and −9.7 kcal/mol and −8.2 and −9.3 kcal/mol, respectively

BIOINFORMATICS: INFLAMMATORY CYTOKINES AND ATTENUATION OF DIABETES HYPERCHOLESTEROLEMIA-INDUCED RENAL INJURY USING MORNING GLORY AND NECKLACE POD EXTRACTS

  Objective: The present research in bioinformatics focuses on pharmacological effects of morning glory and necklace pod ethanolic extracts (MGE and NPE) on some biochemical parameters in high fat diet-induced hypercholesterolemia and streptozotocin-induced hyperglycemia in rats.Methods: Compared to atorvastatin; an anti-hypercholesterolemic (HC) and glibenclamide; an antidiabetic drug. Endothelium activation markers of soluble vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 were determined using enzyme-linked immunosorbent assay. Creatinine, urea, and inflammatory biomarkers; C-reactive protein (CRP) and pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α) and interleukin (IL)-10 levels were also measured in serum of different therapeutic groups.Results: Significant decrease in ICAM-1 level with MGE and NPE supplemented to normal rats as compared to untreated control with percentages decrease 17.80 and 12.00% was observed. Insignificant change was detected in VCAM-1 level. Profound amelioration in CRP, total urea and creatinine levels by NPE treatment. Creatinine, urea, CRP, and TNF-α level were significantly increased in hyperglycemic (HG)-HC rats. However, IL-10 level showed a significant decrease. Meanwhile, histopathological investigation of the kidney and heart was carried out. Image recognition system for kidney and heart images was developed to diagnose their diseases. Tested extract attenuated creatinine, urea, CRP, and TNF-α level. Hyperglycemia and hypercholesterolemia linked kidney disorders were relieved.Conclusion: In vivo oral administration with each extract declared suppression of cytokines mediated inflammation, vascular function leading to infiltration reduction of renal macrophage together with lowering in kidney indices and ameliorate renal tissues architectures in HG-HC rats

Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a–e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c–e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4′-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4′-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4′-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1

In vitro evaluation of electroporated gold nanoparticles and extremely-low frequency electromagnetic field anticancer activity against Hep-2 laryngeal cancer cells

Introduction. The extremely-low frequency electromagnetic field (ELFEMF) has been proposed for use in cancer therapy since it was found that magnetic waves interfere with many biological processes. Gold nanoparticles (Au-NPs) have been widely used for drug delivery during cancer in vitro studies due to their low cytotoxity and high biocompatibility. The electroporation of cancer cells in a presence of Au-NPs (EP Au-NPs) can induce cell apoptosis, alterations of cell cycle profile and morphological changes. The impact of ELFEMF and EP Au-NPs on morphology, cell cycle and activation of apoptosis-associated genes on Hep-2 laryngeal cancer cell line has not been studied yet. Materials and methods. ELFEMF on Hep-2 cells were carried out using four different conditions: 25/50 mT at 15/30 min, while Au-NPs were used as direct contact (DC) or with electroporation (EP, 10 pulses at 200V, equal time intervals of 4 sec). MTT assay was used to check the toxicity of DC Au-NPs. Expression of CASP3, P53, BAX and BCL2 genes was quantified using qPCR. Cell cycle was analyzed by flow cytometry. Hematoxylin and eosin (HE) staining was used to observe cell morphology. Results. Calculated IC50 of DC Au-NPs 24.36 μM (4.79 μg/ml) and such concentration was used for further DC and EP AuNPs experiments. The up-regulation of pro-apoptotic genes (CASP3, P53, BAX) and decreased expression of BCL2, respectively, was observed for all analyzed conditions with the highest differences for EP AuNPs and ELFEMF 50 mT/30 min in comparison to control cells. The highest content of cells arrested in G2/M phase was observed in ELFEMF-treated cells for 30 min both at 25 or 50 mT, while the cells treated with EP AuNPs or ELFEMF 50 mT/15 min showed highest ratios of apoptotic cells. HE staining of electroporated cells and cells exposed to ELFEMF’s low and higher frequencies for different times showed nuclear pleomorphic cells. Numerous apoptotic bodies were observed in the irregular cell membrane of neoplastic and necrotic cells with mixed euchromatin and heterochromatin. Conclusions. Our observations indicate that treatment of Hep-2 laryngeal cancer cells with ELFEMF for 30 min at 25–50 mT and EP Au-NPs can cause cell damage inducing apoptosis and cell cycle arrest

Clinicopathological Significance of Vimentin and Cytokeratin Protein in the Genesis of Squamous Cell Carcinoma of Cervix

Cervical cancer is one of the commonest types of cancers worldwide especially in developing countries. Intermediate filaments protein family has shown a role in the diagnosis of various cancers, but a few studies are available about the vimentin and cytokeratin roles in the cervical cancer. This case control study aimed to interpret the expression of vimentin and cytokeratin proteins in the development and progression of cervical cancer and its correlation with clinicopathological features. The cytoplasmic expression of vimentin was observed in 40% of cases, but not in inflammatory lesions of cervix. It was noticed that vimentin expression was increasing significantly with high grade of the tumour. Cytokeratin expression was observed in 48.33% and it was noticed that the expression was 62.5% in well differentiated (G1), 45% in moderately differentiated (G2), and 41.66% in poorly differentiated carcinoma, yet statistically insignificant. The expression of vimentin and cytokeratin proteins was not significantly associated with age groups. The current findings concluded a possible role of vimentin in the development and progression of cervical cancer and vimentin marker will be useful in the diagnosis and grading of cervical cancer

Intradermal vaccination with hollow microneedles: A comparative study of various protein antigen and adjuvant encapsulated nanoparticles

Drug Delivery TechnologySupramolecular & Biomaterials Chemistr