Aqueous fish extract increases survival in the mouse model of cytostatic toxicity

<p>Abstract</p> <p>Background</p> <p>Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX.</p> <p>Methods</p> <p>A LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (~25 g, n = 70). The animals were divided into four groups, DOX + AOX (n = 20), DOX + saline (NaCl) (n = 30), NaCl + AOX (n = 10) and NaCl only (n = 10). Echocardiography was performed in the separate subgroups (DOX treated n = 6 and controls n = 6) to verify the presence and the grade of acute CHF. The cod extract was delivered by subcutaneously implanted osmotic minipumps over the period of 2 weeks. High-dose injection of DOX was administered to randomly selected animals. The animals received single intraperitoneal injection of DOX (25 mg/kg) and were followed over two weeks for mortality.</p> <p>Results</p> <p>Mortality rate was 68% lower (p < 0.05) in the mice treated with the extract. The analyses of cod extract have shown strong antioxidative effect <it>in vitro</it>.</p> <p>Conclusion</p> <p>The aqueous LMW cod muscles extract decreases mortality in the mouse model of DOX induced acute CHF. This effect may be mediated by cardioprotection through antioxidative mechanisms.</p

Safety, immunogenicity, and reactogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines given as fourth-dose boosters following two doses of ChAdOx1 nCoV-19 or BNT162b2 and a third dose of BNT162b2 (COV-BOOST): a multicentre, blinded, phase 2, randomised trial

Background Some high-income countries have deployed fourth doses of COVID-19 vaccines, but the clinical need, effectiveness, timing, and dose of a fourth dose remain uncertain. We aimed to investigate the safety, reactogenicity, and immunogenicity of fourth-dose boosters against COVID-19.Methods The COV-BOOST trial is a multicentre, blinded, phase 2, randomised controlled trial of seven COVID-19 vaccines given as third-dose boosters at 18 sites in the UK. This sub-study enrolled participants who had received BNT162b2 (Pfizer-BioNTech) as their third dose in COV-BOOST and randomly assigned them (1:1) to receive a fourth dose of either BNT162b2 (30 µg in 0·30 mL; full dose) or mRNA-1273 (Moderna; 50 µg in 0·25 mL; half dose) via intramuscular injection into the upper arm. The computer-generated randomisation list was created by the study statisticians with random block sizes of two or four. Participants and all study staff not delivering the vaccines were masked to treatment allocation. The coprimary outcomes were safety and reactogenicity, and immunogenicity (antispike protein IgG titres by ELISA and cellular immune response by ELISpot). We compared immunogenicity at 28 days after the third dose versus 14 days after the fourth dose and at day 0 versus day 14 relative to the fourth dose. Safety and reactogenicity were assessed in the per-protocol population, which comprised all participants who received a fourth-dose booster regardless of their SARS-CoV-2 serostatus. Immunogenicity was primarily analysed in a modified intention-to-treat population comprising seronegative participants who had received a fourth-dose booster and had available endpoint data. This trial is registered with ISRCTN, 73765130, and is ongoing.Findings Between Jan 11 and Jan 25, 2022, 166 participants were screened, randomly assigned, and received either full-dose BNT162b2 (n=83) or half-dose mRNA-1273 (n=83) as a fourth dose. The median age of these participants was 70·1 years (IQR 51·6–77·5) and 86 (52%) of 166 participants were female and 80 (48%) were male. The median interval between the third and fourth doses was 208·5 days (IQR 203·3–214·8). Pain was the most common local solicited adverse event and fatigue was the most common systemic solicited adverse event after BNT162b2 or mRNA-1273 booster doses. None of three serious adverse events reported after a fourth dose with BNT162b2 were related to the study vaccine. In the BNT162b2 group, geometric mean anti-spike protein IgG concentration at day 28 after the third dose was 23 325 ELISA laboratory units (ELU)/mL (95% CI 20 030–27 162), which increased to 37 460 ELU/mL (31 996–43 857) at day 14 after the fourth dose, representing a significant fold change (geometric mean 1·59, 95% CI 1·41–1·78). There was a significant increase in geometric mean anti-spike protein IgG concentration from 28 days after the third dose (25 317 ELU/mL, 95% CI 20 996–30 528) to 14 days after a fourth dose of mRNA-1273 (54 936 ELU/mL, 46 826–64 452), with a geometric mean fold change of 2·19 (1·90–2·52). The fold changes in anti-spike protein IgG titres from before (day 0) to after (day 14) the fourth dose were 12·19 (95% CI 10·37–14·32) and 15·90 (12·92–19·58) in the BNT162b2 and mRNA-1273 groups, respectively. T-cell responses were also boosted after the fourth dose (eg, the fold changes for the wild-type variant from before to after the fourth dose were 7·32 [95% CI 3·24–16·54] in the BNT162b2 group and 6·22 [3·90–9·92] in the mRNA-1273 group).Interpretation Fourth-dose COVID-19 mRNA booster vaccines are well tolerated and boost cellular and humoral immunity. Peak responses after the fourth dose were similar to, and possibly better than, peak responses after the third dose

Bioactive Compounds from Omani Sea Cucumbers

Antimicrobial, anti-diatom and anti-larval activities of both water soluble (water  extracts) and non-water soluble metabolites (methanol: chlorophorm, 1:1 extracts) of the sea cucumbers Holothuria atra and Holothuria edulis  from Bander AL-Khiran region, Oman were tested in this study. There was no significant effect of  the extracts from sea cucumbers on bacterial (3 reference bacteria from seawater and pathogens  Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa,  Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus epidermidis) and the diatom  Chaetoceros sp. growth. Both water extracts and methanol: chlorophorm extracts caused significant mortality of Artemia salina nauplia. This study suggests that Omani sea cucumbers might be a good  source of toxic anti-larval compounds

Identification and characterization of two amylase producing bacteria Cellulosimicrobium sp. and Demequina sp. isolated from marine organisms

Marine sources have been known to yield novel compounds with a wide range of bioactivity with various commercial applications. In this study, the abilities of bacteria isolated from eight marine organisms to produce α-amylase were examined. All eight organisms were found to harbor amylase producing bacteria. Two bacterial species isolated from the green alga Ulva rigida and the sponge Mycale sp. were further identified and their α-amylases were purified and characterized. The bacterial species isolated from U. rigida and Mycale sp. were identified by DNA sequencing as Cellulosimicrobium sp. and Demequina sp., respectively. Cellulosimicrobium sp. obtained maximum cell growth and amylase production at 29.C and in the presence of lactose as a carbon source. Optimal cell growth and amylase production by Demequina sp. was observed at 35.C. While lactose enhanced cell growth of Demequina sp., maximum amylase production was found when fructose and glycerol were the available sources of carbon. Both strains grew better in the presence of tryptone, whilst peptone stimulated amylase production. Maximal cell growth and amylase production by both of the strains was found at a medium salinity of 3% NaCl.

Identification and characterization of two amylase producing bacteria Cellulosimicrobium sp. and Demequina sp. isolated from marine organisms

Marine sources have been known to yield novel compounds with a wide range of bioactivity with various commercial applications. In this study, the abilities of bacteria isolated from eight marine organisms to produce α-amylase were examined. All eight organisms were found to harbor amylase producing bacteria. Two bacterial species isolated from the green alga Ulva rigida and the sponge Mycale sp. were further identified and their α-amylases were purified and characterized. The bacterial species isolated from U. rigida and Mycale sp. were identified by DNA sequencing as Cellulosimicrobium sp. and Demequina sp., respectively. Cellulosimicrobium sp. obtained maximum cell growth and amylase production at 29.C and in the presence of lactose as a carbon source. Optimal cell growth and amylase production by Demequina sp. was observed at 35.C. While lactose enhanced cell growth of Demequina sp., maximum amylase production was found when fructose and glycerol were the available sources of carbon. Both strains grew better in the presence of tryptone, whilst peptone stimulated amylase production. Maximal cell growth and amylase production by both of the strains was found at a medium salinity of 3% NaCl

Inhibitory effect of known antioxidants and of press juice from herring (Clupea harengus) light muscle on the generation of free radicals in human monocytes

Reactive oxygen species (ROS) can cause oxidative stress, which has been linked to various diseases. It has been suggested that antioxidant-rich foods can reduce such oxidative stress. However, the lack of suitable model systems to screen for in vivo effects of food-derived antioxidants has prevented a clear consensus in this area. In this study, the aim was to use a single-cell model system (human monocyte) to evaluate whether certain pure antioxidants and complex muscle extracts (herring light muscle press juice, PJ) could prevent ROS formation under in vivo like conditions. ROS were excreted from the monocytes upon stimulation with phorbol myristate acetate and were then detected as isoluminol-enhanced chemiluminescence (CL). Adding 2000 units of catalase and 50 units of superoxide dismutase to the monocytes model lowered the CL response by 35 and 86%, respectively. Ascorbate (14.1 mM) lowered the response by 99%, alpha-tocoperhol (188 microM) by 37%, and Trolox (50 microM) by almost 100%. Crude herring PJ gave a dose-dependent reduction in the CL response. At 10, 100, and 1000 times dilution, the PJ reduced the CL signal by 93, 60.5, and 10.6%. PJ fractionated into low molecular weight (LMW) (<1000 Da) and high molecular weight (>3500 Da) fractions decreased the CL response by 52.9 and 71.4%, respectively, at a 100-fold dilution. Evaluation of the PJ samples in the oxygen radical absorbance capacity test indicated that proteins may be the primary radical scavenging compounds of PJ, whereas the ROS-preventing effect obtained from the LMW fraction may also be attributed to other mechanisms. Thus, this study proved that the monocyte assay can be a useful tool for studying whether food-derived antioxidants can limit ROS production under physiologically relevant conditions. It also showed that herring contains numerous aqueous compounds demonstrating antioxidative effects in the monocyte model system