Synthesis of New Azoles and Azolopyrimidines Incorporating Morpholine Moiety as Potent Anti-Tumor Agents

A new series of morpholinyl-chalcones 2a–d was prepared by reaction of 2-oxo-N,4-diarylbut-3-enehydrazonoyl chlorides 1a–d with morpholine. These chalcones were used as a building block for constructing pyrazoles 3a–d and 3,4-dihydropyrimidine-2(1H)-thione 6 via their reaction with phenylhydrazine and thiourea, respectively. Moreover, a new series of azolopyrimidine derivatives 11a,b, 15, 17, 19, and 21 incorporating morpholine moiety were synthesized by reaction of 1-morpholino-4-phenyl-1-(2-phenylhydrazono)but-3-en-2-one (2a) with a number of heterocyclic amines in the presence of a catalytic amount of acetic acid. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data and the mechanisms of their formation were also discussed. All the synthesized compounds were tested for in vitro activities against two antitumor cell lines, human lung cancer (A-549) and human hepatocellular carcinoma (HepG-2) compared with the employed standard antitumor drug (cisplatin) and the results revealed that compounds 6, 8c and 17 have promising activities compared with cisplatin. This work is licensed under a Creative Commons Attribution 4.0 International License

Effect of dietary honey on intestinal microflora and toxicity of mycotoxins in mice

BACKGROUND: Bee honey is a functional food which has a unique composition, antimicrobial properties and bifidogenic effect. In order to assess whether honey can inhibit the toxic effect of mycotoxins, the present study was undertaken. METHODS: Production of biomass and toxins by Aspergillus parasiticus and Aspergillus ochraceus were followed in media without and with honey. Although aflatoxins and ochratoxin A. were administrated to male Swiss albino mice up to 1 μg and 10 ng/kg body weight/day respectively. The experimental animals were fed diets without our with 10% honey for two months. The changes in colonic probiotic bacteria, determintal colon enzyme glucuronidases, and genotoxicity were followed. RESULTS: Addition of 32% in its media increased the biomass of A parasiticus, while the biomass of A. ochraceus decreased and Ochratoxin A. was not produced. When the honey was added at the ratio of 32 and 48% in the medium. No relationship was found between mycelium weight and production of mycotoxins. Oral administration of aflatoxins (mixture of B(1), B(2), G(1) and G(2)) and Ochratoxin A. induced structural and numerical chromosomal aberrations in bone marrow and germ cells of male mice, whereas, honey treatment reduced the genotoxicity of mycotoxins. Also both toxins induced histopathological changes in liver and kidney. Feeding on diet supplemented with honey improved the histopathological changes in case of aflatoxin group, but not in the case of ochratoxin A. group (except of kidney in two cases). No significant differences were found in the activity of colon β-glucuronidase between group fed diet with or without honey. On the other hand, the colon bifido bacteria and lactobacilli counts were increased markedly in group receiving diet supplemented with honey. CONCLUSION: Substituting sugars with honey in processed food can inhibit the harmful and genotoxic effects of mycotoxins, and improve the gut microflora

Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Nanoscaffold on Wound Healing in Irradiated Rats

Background: The effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) and nanoscaffolds were evaluated in enhancing wound healing in irradiated albino rats. Methods: Sixty-four male rats were subjected to 6 grays (Gy) of gamma (γ)-rays. Surgical wounds were created on the rats’ backs and they were randomly assigned to one of four groups (16 each); these were an irradiated control group, which did not receive treatment, an NS group treated with a nanoscaffold, a BM-MSC group injected subcutaneously with 1 million BM-MSCs, and a combination BM-MSC+NS group treated with BM-MSCs and a nanoscaffold. Wound healing was measured clinically and histologically. Results: The greatest reduction of anteroposterior wound dimensions was recorded in the BM-MSC+NS group (-69.79 ±19.27), followed by the NS group (-61.12 ±17.32), then the BM-MSC group (-43.89 ±20.04), and the least decrease was observed in the control group (-16.69 ±12.18) (p = 0.001). Meanwhile, the greatest reduction of lateral wound dimensions was recorded in the NS group (-60.41 ±11.80), followed by the BM-MSC+NS group (-45.23 ±62.82), then the BM-MSC group (-41.07 ±24.78), with the control group demonstrating the least reduction (-16.49 ±20.90) (p = 0.008). Histologically, the combination group demonstrated the best healing results compared to the other groups. Conclusion: Nanoscaffolds and/or BM-MSC transplantation improved wound healing and regeneration in irradiated rats, providing possible therapeutic strategies for delayed wound healing during radiotherapy

Rheumatological manifestations in patients with malignancies: Relation to immune modulation therapy

Background: The relation between malignancies and rheumatic diseases (RDs) is complex with commonly shared symptoms. Rheumatological manifestations of malignancies may present as paraneoplastic syndromes and could follow chemotherapy. Aim of the work: to investigate rheumatic manifestations of patients with hematologic or solid malignancies and the relation to immune-modulation therapy. Patients and methods: The study included 25 patients with hematological and another 25 with solid malignancies. Patients were subjected to medical history, recording medications received, musculoskeletal examination and laboratory assessment. Results: The mean age and F:M of patients with hematological (43.7 ± 16.04 y and F:M 1.5:1) was significantly lower than those with solid (53.6 ± 14.3 y and F:M 7.3:1) malignancies (p = 0.025 and p = 0.024). Rheumatological manifestations as the first presentation was significantly higher in patients with haematological (60%) compared to solid (20%) malignancies (p = 0.004). Articular involvement was the commonest rheumatological manifestation (72%) followed by mucocutaneous (18%), oral/genital ulcers (10%), thromboembolic events (10%), Raynauds (8%), dry eyes (8%), myositis (6%) and myalgia (4%). The total leucocytic count and serum uric acid were significantly lower in patients with solid tumors (p = 0.045 and p = 0.026 respectively) and autoimmune markers were similar. Dry eye (16.7%), oral/genital ulcers (20.8%) and Raynaud‘s (16.7%) was present only in patients receiving anti-cancer treatment (n = 24). Paradoxically, arthritis was more frequent in those not receiving chemotherapy (n = 17) while myalgia (25%) was evident in those receiving checkpoint inhibitors (n = 8). Conclusion: Rheumatological manifestations occur with solid and hematological malignancies before or throughout the disease course and the most frequent was articular. Myalgia was associated with checkpoint inhibitors

Maxillary distraction of cleft lip and palate patients by internal maxillary distractors

In the past decade, considerable progress has been made in the development of Brillouin scattering (BS) as a technique for the nondestructive characterization of materials. With the advent of high resolution and high contrast multipass tandem Fabry-Perot interferometry [1], BS has been applied to the measurement of the near-surface elastic properties of opaque materials [2], thin supported films [3] and interfaces [4], making use of various guided and localized acoustic modes including Rayleigh waves, pseudo-surface acoustic waves (p-SAW), Sezawa waves and Stoneley waves. By identifying the presence of particular acoustic modes in BS spectra, and comparing these with calculation, one can extract information pertaining to the physical properties of the system