Abstract Heat stress (HS) is an environmental challenge affecting animals' health, productivity and welfare. This work aimed to inspect the protective effect of zinc oxide nanoparticles (ZnNPs) and/or prodigiosin (PRG) against inflammation, immune dysfunction, oxidative stress and endoplasmic reticulum (ER) stress triggered by HS in growing rabbits. Growing weaned rabbits (one hundred males, 35 days of age) were randomly assigned into four groups. The first group fed a basal diet without supplementation and the 2nd, 3rd, and 4th groups fed diets containing zinc oxide nanoparticles (ZnNPs, 50mg/kg diet), prodigiosin (PRG, 100 mg/kg diet) or their mixture (ZnPRG) under HS conditions for eight successive weeks. The dietary inclusion with ZnNPs and/or PRG significantly boosted FBW (final body weight), CBWG (cumulative body weight gain), and FCR (feed conversion ratio) and had no substantial impacts on the CFI (cumulative feed intake) as compared with those in HS one. All supplemented treatments significantly unveiled an increase in the values of RBCs, hemoglobin, and platelets and significantly decreased in WBCs, basophils and monocytes with non-statistically effects on hematocrit, MCV, MCHC, neutrophils and eosinophils. Compared with the HS group, all supplemental groups showed a significant reduction in TNFα, IL4, IFN-γ, TLR-4 and amyloid A levels and DNA damage markers (Ohdg) and significantly increased in the levels of NO and lysosome activity. Rabbits in the ZnPRG group had significantly higher Ig G and Ig M levels than in other groups. The highest value of CAT and GSH levels were found in rabbits received the mixture of ZnNPs (50mg) and PRG (100mg) in their diets under elevated temperatures. Additionally, both treatments, PRG and ZnNPS, significantly (P<0.001) reduced the values of MDA and MYO, while all treated groups had significantly reduced PC contents compared with the HS group. Co-supplement with ZnPRG showed a considerable restoration in the higher immune expression of reticulum oxidative such GRP78 and IRE1 in hepatic tissues induced by HS conditions. The mixture of ZnNPs and PRG presented more robust effects in mitigating the adverse impacts of HS in rabbits compared with the individual treatments. Collectively, ZnNPs and/or PRG alleviated oxidative stress and DNA damage. In addition, it enhanced the antioxidant capacity and immune function, and downregulated ER stress such as GRP78 and IRE1 signaling in the hepatic tissues of stressed rabbits.

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Use of zinc nanoparticles and/or prodigiosin to mitigate heat stress in rabbits

Campylobacter hyointestinalis is a causative agent of enteritis, proctitis, human gastroenteritis, and diarrhea. Reported transmission is from pigs to humans. Link with gastrointestinal carcinoma has also been established in non-Helicobacter pylori patients carrying this strain. The genome size of the strain LMG9260 is 1.8 MB with 1785 chromosomal and seven plasmid proteins. No therapeutic targets have been identified and reported in this bacterium. Therefore, subtractive computational screening of its genome was carried out for the purpose. In total, 31 such targets were mined and riboflavin synthase was utilized for screening natural product inhibitors against it. Among more than 30,000 screened natural compounds from the NPASS library, three (NPC472060, NPC33653, and NPC313886) were prioritized to have the potential to be developed into new antimicrobial drugs. Dynamics simulation assay along with other relevant parameters like absorption, toxicity, and distribution of the inhibiting compounds were also predicted and NPC33653 was identified as having the best drug-like properties among the prioritized compounds. Thus, it has potential to be pursued further for the inhibition of riboflavin synthesis in C. hyointestinalis for subsequent obstruction of its growth and survival.Communicated by Ramaswamy H. Sarma.

Subtractive sequence-mediated therapeutic targets from the conserved gene clusters of Campylobacter hyointestinalis and computational inhibition assessment.

It is well-acknowledged that 'combination therapy' of antibiotics is indispensable for the treatment of patients suffering from serious bacterial infections. Therefore, it is of interest to collect data from the in vitro tests using 'rifampicin-cefotaxime' and 'rifampicin-tetracycline' combination regimens against multi drug resistant Escherichia coli and Klebsiella pneumoniae strains of nosocomial source in order to determine the effectiveness of the combination therapy. The minimum inhibitory concentration (MIC) values for cefotaxime, tetracycline and rifampicin antibiotics were found to be comparatively high for each of the antibiotics when given individually. However, carefully prepared combination-regimens exhibited significant inhibitory effect on the same bacterial isolates. DNA fragmentation study confirmed that 'rifampicin-cefotaxime' and 'rifampicin-tetracycline' combination-regimens could cause breakage of the bacterial DNA. Thus, we show that combination-regimens namely, 'rifampicin-cefotaxime' and 'rifampicin-tetracycline' were found to be capable of maintaining rifampicin susceptibility in the E. coli and K. pneumoniae strains. However, this susceptibility was not maintained by only rifampicin. More data using animal model experiments are needed for confirming and deriving translational benefits from these findings in future.

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Effect of rifampicin combination-regimens against multi-drug resistant strains in North India

Unveiling the multitargeted repurposing potential of taxifolin (dihydroquercetin) in cervical cancer: an extensive MM\GBSA-based screening, and MD simulation study

Y. S. Alghamdi

Papers

Use of zinc nanoparticles and/or prodigiosin to mitigate heat stress in rabbits

Subtractive sequence-mediated therapeutic targets from the conserved gene clusters of Campylobacter hyointestinalis and computational inhibition assessment.

Effect of rifampicin combination-regimens against multi-drug resistant strains in North India

Unveiling the multitargeted repurposing potential of taxifolin (dihydroquercetin) in cervical cancer: an extensive MM\GBSA-based screening, and MD simulation study