Hydroferrate Fluid,MRN-100, Provides Protection against Chemical-Induced Gastric and Esophageal Cancer in Wistar Rats

In the current study, we examined the protective effect of hydroferrate fluid MRN-100 against the carcinogen methylnitronitrosoguanidine (MNNG)-induced gastric and esophageal cancer in rats. MRN-100 is an iron-based compound composed of bivalent and trivalent ferrates. At 33 weeks post treatment with MNNG, rats were killed and examined for the histopathology of esophagus and stomach; liver, spleen, and total body weight; and antioxidant levels in the blood and stomach tissues. Results showed that 17/20 (85%) gastroesophageal tissues from carcinogen MNNG-treated rats developed dysplasia and cancer, as compared to 8/20 (40%) rats treated with MNNG plus MRN-100. In addition, MRN-100 exerted an antioxidant effect in both the blood and stomach tissues by increasing levels of GSH, antioxidant enzymes SOD, CAT, and GPx, and total antioxidant capacity (TAC) level. This was accompanied by a reduction in the total free-radical and malondialdehyde levels. Furthermore, MRN-100 protected against body and organ weight loss. Thus, MRN-100 exhibited significant cancer chemopreventive activity by protecting tissues against oxidative damage in rats, which may suggest its effectiveness as an adjuvant for the treatment of gastric/esophageal carcinoma.     

Discovery of new VEGFR-2 inhibitors based on bis([1, 2, 4]triazolo)[4,3-a:3',4'-c]quinoxaline derivatives as anticancer agents and apoptosis inducers

Herein, a new wave of bis([1, 2, 4]triazolo)[4,3-a:3'',4''-c]quinoxaline derivatives have been successfully designed and synthesised. The synthesised derivatives were biologically investigated for their cytotoxic activities against HepG2 and MCF-7. Also, the tested compounds were further examined in vitro for their VEGFR-2 inhibitory activity. The most promising derivative 23j was further investigated for its apoptotic behaviour in HepG2 cell lines using flow cytometric and western-plot analyses. Additional in-silico studies were performed to predict how the synthesised compounds can bind to VEGFR-2 and to determine the drug-likeness profiling of these derivatives. The results revealed that compounds 23a, 23i, 23j, 23l, and 23n displayed the highest antiproliferative activities against the two cell lines with IC₅₀ values ranging from 6.4 to 19.4 µM. Furthermore, compounds 23a, 23d, 23h, 23i, 23j, 23l, 23 m, and 23n showed the highest VEGFR-2 inhibitory activities with IC₅₀ values ranging from 3.7 to 11.8 nM, comparing to sorafenib (IC₅₀ = 3.12 nM). Moreover, compound 23j arrested the HepG2 cell growth at the G2/M phase and induced apoptosis by 40.12% compared to the control cells (7.07%). As well, such compound showed a significant increase in the level of caspase-3 (1.36-fold), caspase-9 (2.80-fold), and BAX (1.65-fold), and exhibited a significant decrease in Bcl-2 level (2.63-fold).     

The ontogeny of appendages and carapace of Neonesidea schulzi (Ostracoda: Bairdiidae) from the Red Sea coast,Egypt

The ostracod genus Neonesidea is broadly distributed in shallow marine waters. The ontogeny of the N. schulzi (Bairdiidae) is described in detail by studying the development of the appendages and variations in carapace form, size and structure. Neonesidea schulzi has eight post-embryonic instars, and a gap in its ontogenetic development during instar A-6, where no new Anlage is added. The Anlagen of the copulatory organs and the forked terminal claw of second antenna appear in the seventh (A-1) instar, and the first thoracic legs of podocopid ostracods are shown to descend from the thoracic region. For the first time in ostracods, observations of moulting from sixth and seventh instars are presented.     

The anti-tumour effect of induced pluripotent stem cells against submandibular gland carcinoma in rats is achieved via modulation of the apoptotic response and the expression of Sirt-1, TGF-β, and MALAT-1 in cancer cells

Molecular and Cellular Biochemistry - The era of induced pluripotent stem cells (iPSCs) was used as novel biotechnology to replace embryonic stem cells bypassing the ethical concerns and problems...     

Diacerein niosomal gel for topical delivery: development,in vitro and in vivo assessment

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box–Behnken design was used to investigate the effect of charge-inducing agent (X₁), surfactant HLB (X₂) and sonication time (X₃) on the vesicle size (Y₁), entrapment efficiency (Y₂) and cumulative drug released (Y₃). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72?µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8?h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p?相似文献   

Sunlight-driven rapid and facile synthesis of Silver nanoparticles using Allium ampeloprasum extract with enhanced antioxidant and antifungal activity

Green nanotechnology has acquired immense demand due to its cost-effective, eco-friendly and benevolent approach for the synthesis of nanoparticles. Among the biological methods, plants aid as a significant green resource for synthesizing nanoparticles that are safe and non-toxic for human use. In the present investigation, Silver nanoparticles (AgNPs) were synthesized using bulbs extract of Allium ampeloprasum under the influence of sunlight irradiation and characterized using different techniques. Distinct in-vitro assays were performed to test the antioxidant and anticandida potential of the synthesized AgNPs. Results suggested the efficient and rapid sunlight-driven synthesis of AgNPs using A. ampeloprasum extract. UV–Vis spectrum showed absorption peak at 446 nm which confirmed the formation of AgNPs. FTIR analysis suggested the presence of functional groups associated with flavonoids and sulfur compounds in A. ampeloprasum extract. The synthesized AgNPs showed Face Centred Cubic (FCC) structure with an average size of 35 nm. Spherical, quasi spherical, triangular and ellipsoidal morphology of the NPs were observed from the TEM micrograph. The synthesized AgNPs showed pronounced free radical scavenging potential for DPPH, ABTS?+ and H₂O₂ radicals. The anticandida potency of the synthesized AgNPs was observed as follows: C. albicans ≥ C. tropicalis ≥ C. glabrata ≥ C. parapsilosis ≥ C. krusei. Results showed that sunlight driven nanoparticle synthesis of AgNPs is rapid, facile and exhibit enhanced antioxidant and antifungal activity.     

Studies on the epimerization of 2-acetamido-2-deoxyhexoses: preparation of 2-acetamido-2-deoxy-d-[2-3H]-glucose and -mannose

Epimerization of either 2-acetamido-2-deoxy-d-glucose (1) or 2-acetamido-2-deoxy-d-mannose (2) in basic tritium oxide gave 2-acetamido-2-deoxy-d-[2-³H]-glucose (3) and 2-acetamido-2-deoxy-d[2-³H]mannose (4). In both cases, compound 3 was isolated in higher proportion and higher specific activity than 4. The mechanism of the epimerization of 1 and 2 is discussed.     

Integration of LC/MS,NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti-SARS-CoV-2 Activity

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC₅₀ 8.231±0.04 μg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.     

Infliximab substantially re-silenced Wnt/β-catenin signaling and ameliorated doxorubicin-induced cardiomyopathy in rats

The release of inflammatory cytokines, namely tumor necrosis factor-α (TNF-α), plays an important role in the pathogenesis of cardiomyopathy. TNF-α increases in plasma and in myocardium of heart failure patients. We aimed to investigate the role of TNF-α inhibitor (infliximab; IFX) in regulating dilated cardiomyopathy (DCM) induced in rats. DCM was induced in rats by doxorubicin (DOX; 3.5 mg. kg⁻¹, i.p) twice weekly for 3 weeks (21 mg. kg⁻¹ cumulative dose). DCM rats were treated with RPL (1 mg. kg⁻¹ orally, daily), IFX (5 mg. kg⁻¹; i.p. once) or their combination for 4 weeks starting next day of last DOX dose. Echocardiography was conducted followed by a collection of blood and left ventricle (LV) for biochemical and histological investigations. DCM rats revealed deteriorated cardiac function (increased CK-MB activity, LVIDs, LVIDd, ESV, and EDV, while decreased EF% and FS%), hypertrophy (increased HW/TL, β-MHC, and α-actin), inflammation (increased IL-1β, IL-6, and TNF-α). The activation of Wnt/β-catenin along with increased gene expression of RAS components (RENIN, ACE, and AT1) were evident. LV architecture also revealed abnormalities and some degree of fibrosis. Treatment with RPL and/or IFX suppressed TNF-α and consequently improved most of these parameters suppressing Wnt/β-catenin/RAS axis. Combined RPL and IFX treatment was the best among all treatments. In conclusion, Wnt/β-catenin/RAS axis is implicated in DOX-induced cardiomyopathy. The upstream TNF-α was proved for the first time in-vivo to stimulate this axis where its inhibition by RPL or IFX prevented DCM. Targeting this axis at two points using RPL and IFX showed better therapeutic efficacy.