Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway.

INTRODUCTION: Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals. AIM: This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated. METHOD: Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA. RESULTS: Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1ß. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death. CONCLUSION: This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.

Bioactive sulfonyl metabolites from the Red Sea endophytic fungus Penicillium aculeatum.

Two new sulfonyl metabolites, pensulfonoxy (1) and pensulfonamide (2), together with four known metabolites were obtained from the fermentation extract of Penicillium aculeatum, an endophytic fungus isolated from the marine red alga Laurencia obtusa. The structures of the compounds were established on the basis of extensive NMR and MS spectroscopic analysis. The ethyl acetate extract exhibited potent antibacterial inhibitory activity against Escherichia coli, while compound 2 exhibited antifungal activity against Candida albicans with inhibition diameters of 20.5 and 18.0 mm, respectively. Moreover, compound 2 also displayed the most potent preferential cytotoxicity against MCF-7, while compound 1 displayed relatively mild activity against HCT-116 with IC50 values of 2.18 and 5.23 µM, respectively, compared to the drug control, paclitaxel.

Prevalence of methicillin-resistant coagulase-negative staphylococci among Egyptian patients after surgical interventions.

Coagulase-negative staphylococci (CoNS) are frequently isolated from wound infections. There are limited data examining the prevalence of methicillin-resistant CoNS (MRCoNS) among Egyptian patients after surgery. Thus, we studied 208 hospitalised patients, who had skin and soft tissue infections (SSTIs) due to various causes. Samples were cultured for isolation and identification of CoNS and isolates were screened for susceptibility against 23 different antimicrobials. Out of 241 Staphylococcal isolates, 114 (47.3%) were CoNS. The prevalence of MRCoNS among surgical site infection, diabetic foot, abscess, and burn patients was 13.4%, 11.5%, 15.6%, and 10.3%, respectively. The lowest resistance of the 27 identified MRCoNS isolates was to vancomycin, amikacin and gatifloxacin (7% each). We conclude that CoNS isolates are major pathogens associated with wound infections at our institution and MRCoNS probably poses a substantial threat for patients in Egypt, though most MRCoNS isolates demonstrated susceptibility to vancomycin.

Candelariella vitellina extract triggers in vitro and in vivo cell death through induction of apoptosis: A novel anticancer agent.

Candelariella vitellina is common green-yellow lichen found on barks, wood, and rocks in Japanese forests. To investigate the mechanism of its anticancer potential, C. vitellina (80% MeOH/H2O) extract was prepared. High-performance liquid chromatography-high-resolution electrospray ionization mass spectrometry analysis revealed seven new compounds and 11 natural compounds of terpenes and polyketides. In vitro cytotoxicity analysis of Caco-2 cells exhibited an IC50 of 125 ±â€¯4.1 µg/mL. No significant cytotoxicity was observed in vitro in normal human peripheral lymphocytes. Both the IC25 and IC50 were determined to explore the potent anticancer potential in this study. C. vitellina exhibited a mitochondrial P53-independent apoptotic effect with negative P53 expression and an elevated BAX/BCL2 ratio as well as upregulated CASP3 mRNA expression. Similarly, in vivo analysis showed the same pattern of anticancer potential but was dependent on the P53 expression. Furthermore, C. vitellina induced antioxidative conditions in vitro and in vivo. The decreased invasion of tumor cells in vivo and increased apoptotic features in vitro and in vivo suggest the moderate to strong apoptotic anticancer potential of C. vitellina. However, further studies are needed to determine the extent and mechanism of action on different cell lines to support the anticancer properties of this lichen.

Ganoderma applanatum secondary metabolites induced apoptosis through different pathways: In vivo and in vitro anticancer studies.

Ganoderma applanatum is a widely distributed saprobic or parasitic mushroom, it was found at the bases of decaying logs in Hakozaki Higashi-ku Fukuoka-shi. Japan. The mushroom was extracted with 80% methanol, and LC-HRMS analysis was conducted to illustrate the bioactive ingredients. The cytotoxicity of the total metabolite extract was evaluated against human colon cancer cell line (Caco-2) which showed IC50 value of 160 ±â€¯4.08 µg/ml. G. applanatum methanolic extract caused different morphological alterations and increased glutathione level in the treated cells. Interestingly, G. applanatum increased Bax/Bcl-2 ratio significantly (P ˂ 0.05) at concentrations of 80 and 160 µg/ml on Caco-2 undergoing apoptotic p53-independent pathway with lake expression of p53 protein and up-regulated Cas-3 mRNA. The in vivo study on solid Ehrlich tumor (SEC) revealed a decrease in the volume of the developed tumor mass after five days of G. applanatum (200 µg/ml) treatment. The apoptotic p53-dependant pathway was confirmed by mRNA Bax/Bcl-2 increased ratio in addition to p53 and Cas-3 up-regulation. In conclusion, G. applanatum could exert apoptotic antitumor properties in Caco-2 by p53-independent pathway and p53-dependant in SEC. The findings proved that G. applanatum can be a promising candidate as alternative or co-anticancer medications.

Polysaccharide extracts of the brown alga Sargassum asperifolium possess in vitro cancer chemopreventive properties.

The cancer chemopreventive activity of the polysaccharide extracts (E1-E4) of Sargassum asperifolium, a brown alga in Red Sea shores in Egypt, was investigated. Tumour anti-initiation activity (the modulation of carcinogen metabolism) indicated that E3 and E4 were potent anti-initiators by inhibiting the carcinogen activator cytochrome P450-1A, and enhancing carcinogen detoxification enzymes glutathione-S-transferase. Only E4 significantly enhanced quinone reductase activity. All polysaccharide extracts possessed anti-promotion property by their anti-inflammatory activity. E3 and E4 dramatically induced the growth of spleen macrophages. E2, E3 and E4 significantly inhibited nitric oxide generation from lipopolysaccharide (LPS)-stimulated spleen macrophages, while E1, E3 and E4 led to significant inhibition of LPS-induced tumour necrosis factor-α. The extracts E1, E2 and E4 showed cytotoxicity against HepG2 cells, where E2 and E4 induced cell death due to apoptosis. In conclusion, E3 and E4 are promising cancer chemopreventive extracts, since they had tumour anti-initiating activity via their protective modulation of carcinogen metabolism.

Prevalence of methicillin resistant Staphylococcus aureus among Egyptian patients after surgical interventions.

BACKGROUND: Staphylococcus aureus (S. aureus) is isolated frequently from surgical site infections and other soft tissue infections. There are limited data examining the prevalence of methicillin resistant S. aureus (MRSA) among Egyptian patients after surgery. The current study determined the prevalence of MRSA isolated from surgical site and soft tissue infections at Minia University Hospital (MUH), determined their susceptibility to ß-lactams and other antimicrobials, and examined their mecA gene expression. METHODS: A total of 208 hospitalized patients attending the General Surgery Department at MUH were enrolled and all had skin and soft tissue infections (SSTIs) of different causes. These 208 patients (143 males and 65 females) were suffering from surgical site infection (SSI; n=82), diabetic foot (n=52), abscess (n=45), or burn (n=29) infections. Samples were cultured on different media for isolation and identification of S. aureus and the isolates were screened for antibiotic susceptibility. All MRSA isolates were tested by polymerase chain reaction to detect the mecA gene responsible for methicllin resistance. RESULTS: 241 Staphylococcal species represented the most common isolates (64.8%) among 371 collected isolates from the 208 patients. Out of the 241 staphylococcal isolates, 127 were S. aureus (61% of the total patients). The prevalence of S. aureus among SSI, diabetic foot, abscess, and burn patients were 59%, 75%, 56%, and 52%, whereas that of MRSA was 16%, 17%, 13%, and 10%, respectively. MRSA isolates (n=31; 15% of patients) showed multiple resistance to at least one member of the antimicrobial groups tested with an average resistance to 6.6±1.9 antimicrobial groups. Polymerase chain reaction data showed that only 29 isolates of the MRSA isolates (94%) were positive for mecA gene. CONCLUSIONS: Staphylococcus aureus isolates are the major pathogens responsible for wound and surgical site infections at MUH and MRSA are a potential threat for wound patients in Egypt.

Scaling up, characterization of levan and its inhibitory role in carcinogenesis initiation stage'.

Honey isolate Bacillus subtilis M was cultivated in shake flasks and in 16-l bioreactor cultures to investigate cell growth, bio-metabolites production kinetics and bioprocess scalability. The respective maximal levan and levansucrase productions of 59.5 g/l and 74.1 U/ml were achieved in bioreactor cultures under pH controlled condition (pH=7.0) after only 24 h. Crude levan (levE) was isolated, characterized and fractionated into F1, F2, and F3 with different molecular weight (21.8, 13.118, 9.53 kDa). (1)H NMR and (13)C NMR spectroscopy proved that LevE and their fractions were mainly ß-(2, 6)-linked levan-type polysaccharide. The cancer chemo-preventive activity indicated that the levE and its fraction 3 were promising inhibitors of cytochrome P-450 1A activity, inducers of glutathione-S-transferase activity in Murine hepatomaHepa1c1c7cells and possessed highest radical scavenging affinity to both ROO and OH. They inhibited the induced-DNA fragmentation. None of the tested samples triggered apoptosis or necrosis in splenocytes, except F2.

Anti-genotoxic effect of the Sargassum dentifolium extracts: prevention of chromosomal aberrations, micronuclei, and DNA fragmentation.

The alga Sargassum dentifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown seaweed in red sea shores in Egypt. This work aimed to extract different water-soluble polysaccharide extracts (E1, E2, and E3) from S. dentifolium and to investigate their protective effect against cyclophosphamide (CP)-induced genotoxicity. Mice bone marrow cells (BMCs) were collected and analyzed for the chromosomal aberration, micronucleated BMCs (MN-BMCs), the mitotic index, DNA fragmentation by comet assay, and histone deacetylases (HDACs), and radical scavenging capacity of extracts was evaluated by the oxygen radical absorbance capacity assay. The results indicated that E2 and E3 significantly inhibited CP-induced multiple chromosomal aberrations, where E1 and E3 significantly suppressed the number of CP-induced formation of tetraploidy. The extracts prohibited the cytotoxic effect of CP and recovered the mitotic activity, whereas E1 possessed the highest recovery and mitosis. In absence of MN, CP induced formation of bi- and poly-nucleated BMCs. E1 prohibited CP-induced formation of bi-nucleated BMCs, while E2 and E3 prohibited CP-induced formation of poly-nucleated BMCs. CP-induced MN-BMCs were accompanied with mono-, bi- and poly-nucleated cells. E1 and E3 remarkably suppressed mono-nucleated MN-BMCs, while E2 inhibited bi-nucleated MN-BMCs. All the extracts significantly inhibited the CP-induced formation of poly-nucleated MN-BMCs. CP-induced DNA fragmentation was inhibited by all extracts, where E1 was the strongest inhibitor as concluded from the comet tail moment. All the extracts were strong OH scavengers, while only E3 was ROO scavenger. The results revealed a drastic decline in HDACs activity by E1 and E3. In conclusion, S. dentifolium polysaccharide extracts E1 and E3 possessed a potential anti-genotoxic and a promising anti-mutagenic activity.

Hepatitis C virus NS3-NS4A protease inhibitors from the endophytic Penicillium chrysogenum isolated from the red alga Liagora viscida.

Hepatitis C virus (HCV) NS3-NS4A protease is an attractive target for anti-HCV agents because of its important role in replication. In this work, we demonstrated that the ethyl acetate extract of the endophytic fungus Penicillium chrysogenum exhibited a potent activity against HCV NS3-NS4A protease with an IC50 value of 20 microg/ml. The fungus was isolated from the red alga Liagora viscida and identified by its morphology and 18S rDNA. Large-scale fermentation of the fungus in Czapek's peptone liquid medium followed by chromatographic purification of the active extract from the liquid medium allowed the isolation of twelve known metabolites. The biological properties of the isolated compounds were explored for anti-HCV protease as well as antimicrobial and anticancer activities. A computational docking study of the active isolated compounds against HCV protease was used to formulate a hypothetical mechanism for the inhibitory activity of the active compounds on the tested enzymes.

OPTIMIZATION OF SOME HEAVY METALS BIOSORPTION BY REPRESENTATIVE EGYPTIAN MARINE ALGAE(1).

Marine algae-as inexpensive and renewable natural biomass-have attracted the attention of many investigators to be used to preconcentrate and biosorb many heavy metal ions. Impressed by this concept, the metal uptake capacity of Egyptian marine algae was examined using representatives of green and brown algae, namely, Ulva lactuca L. and Sargassum latifolium (Turner) C. Agardh, respectively. The biosorption efficiencies of Cu(2+) , Co(2+) , Ni(2+) , Cd(2+) , Hg(2+) , Ag(2+) , and Pb(2+) ions seem to depend on the type of the algae used as well as the conditions under which the uptake processes were conducted. It was demonstrated that a pH range of 7.5-8.8 was optimum for the removal of the tested metals. Similarly, the uptake process was markedly accelerated during the first 2 h using relatively low metal level and sufficient amounts of the dried powdered tested algae.

Preparation and antimicrobial activity of poly (vinyl chloride)/gelatin/montmorillonite biocomposite films.

The aim of this study was using a novel antimicrobial thermoplastic plasticizer based on aliphatic anhydride derivative dodecenyl succinic anhydride (DSA) for blending poly (vinyl chloride), PVC, with gelatin in presence of montmorillonite (MMT) using Brabender via polymer melting technique. This anhydride-based plasticizer blended the membrane ingredients homogenously under melting process. The used plasticizer exhibited high performance antimicrobial potency for some biomedical and industrial applications. The prepared biocomposite films were evaluated for antimicrobial activity using agar disc diffusion method against gram-positive and gram-negative bacteria such as: Staphylococcus aureus (S. aureus), Klebsiella pneumonia (K. pneumonia), Bacillus cereus (B. cereus), Bacillus subtilis (B. subtilis) and Escherichia coli (E. coli). The majority of these biocomposites, except the plasticized PVC with DOP, have shown inhibitory effect at different concentrations (1.0-20) mg/ml against all above mentioned bacteria. However, C. albicans and A. niger were the most resistant strains.

In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium.

Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 microg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-alpha (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia.