Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

The Natural Helper approach to culturally responsive disease management: protocol for a type 1 effectiveness-implementation cluster randomised controlled trial of a cultural mentor programme.

INTRODUCTION: Chronic disease is a leading cause of death and disability that disproportionately burdens culturally and linguistically diverse (CALD) communities. Self-management is a cornerstone of effective chronic disease management. However, research suggests that patients from CALD communities may be less likely to engage with self-management approaches. The Natural Helper Programme aims to facilitate patient engagement with self-management approaches (ie, 'activation') by embedding cultural mentors with lived experience of chronic disease into chronic disease clinics/programmes. The Natural Helper Trial will explore the effect of cultural mentors on patient activation, health self-efficacy, coping efforts and health-related quality of life (HRQoL) while also evaluating the implementation strategy. METHODS AND ANALYSIS: A hybrid type-1 effectiveness-implementation cluster-randomised controlled trial (phase one) and a mixed-method controlled before-and-after cohort extension of the trial (phase 2). Hospital clinics in highly multicultural regions in Australia that provide healthcare for patients with chronic and/or complex conditions, will participate. A minimum of 16 chronic disease clinics (clusters) will be randomised to immediate (active arm) or delayed implementation (control arm). In phase 1, the active arm will receive a multifaceted strategy supporting them to embed cultural mentors in their services while the control arm continues with usual care. Each cluster will recruit an average of 15 patients, assessed at baseline and 6 months (n=240). In phase 2, clusters in the control arm will receive the implementation strategy and evaluate the intervention on an additional 15 patients per cluster, while sustainability in active arm clusters will be assessed qualitatively. Change in activation over 6 months, measured using the Patient Activation Measure will be the primary effectiveness outcome, while secondary effectiveness outcomes will explore changes in chronic disease self-efficacy, coping strategies and HRQoL. Secondary implementation outcomes will be collected from patient-participants, mentors and healthcare providers using validated questionnaires, customised surveys and interviews aligning with the Reach, Effectiveness, Adoption, Implementation, Maintenance framework to evaluate acceptability, reach, dose delivered, sustainability, cost-utility and healthcare provider determinants. ETHICS AND DISSEMINATION: This trial has full ethical approval (2021/ETH12279). The results from this hybrid trial will be presented at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000697785.

Arg753Gln Polymorphisms in the Toll-Like Receptor 2 Gene are Associated with Cytomegalovirus Infection in Egyptian Bone Marrow Recipients.

BACKGROUND: Previous studies have shown that cytomegalovirus (CMV) induced innate immune response via activation of Toll-like receptor 2 (TLR2). The association between CMV among specific single-nucleotide polymorphisms (SNPs) in the TLR2 gene was also investigated. OBJECTIVE: This study investigated the relationship between specific SNPs in the TLR2 gene (G>A), TLR2-Arg753Gln (rs5743708), and CMV replication after bone marrow transplantation. METHODS: The TLR2-Arg753Gln SNP was genotyped in 181 patients after bone marrow transplantation: 83 and 98 patients with and without CMV infection, respectively. CMV load was determined in serially collected blood samples using real-time PCR. Genotyping was performed using specific sequence primer PCR (SSP-PCR), and the results were confirmed by restriction fragment length polymorphism (RFLP) analysis of the PCR-amplified fragments for GG (wild type), GA and AA identification. RESULTS: Roughly, 85% of the patients screened for the presence of the TLR2-Arg753Gln were GG homozygous, and 15% were GA heterozygous; no patients were homozygous for the mutant allele (A). The GA heterozygous allele was more frequent in the CMV-infected group after bone marrow transplantation. CONCLUSION: To our knowledge, this is a novel observation that supports the notion that the functional missense mutation (TLR2-Arg753Gln polymorphism) is possibly associated with CMV replication after bone marrow transplantation. This suggests a role for TLR2 in the innate immune response of human CMV infection in Egyptian bone marrow recipients.

New quinoline-2-one/pyrazole derivatives; design, synthesis, molecular docking, anti-apoptotic evaluation, and caspase-3 inhibition assay.

We report the synthesis of new quinoline-2-one/pyrazole hybrids and their antiapoptotic activity. This effect was studied in sight of decreasing tissue damage induced by I/R in colon of rats using N-acetylcysteine (NAC) as anti-apoptotic reference. Compounds 6a, 6c and 6f showed significant improvement for oxidative stress parameters MDA, SOD, GSH and NOx in comparison with model group and greater than the reference NAC (N-acetylcysteine), whereas compounds 6d and 6e exhibited weaker antioxidant activity when compared with the reference NAC. Moreover, compounds 6a, 6c and 6f showed significant decrease in inflammatory mediators TNFα and CRB greater than NAC when compared to the model group especially compound 6c whose found CRB conc 1.90 (mg/dL) in comparison to NAC of conc 2.13 mg/dL. Additionally, colonic histopathological investigation was performed to all targeted compounds that indicates H&E sections of compounds 6a and 6f revealed apparent normal colonic cells while compound 6e showed dilated blood vessels with more apoptotic cells if compared with NAC. Caspase-3 inhibition assay revealed that compounds 6a, 6b and 6d weaken caspase-3 expression to an extent higher than NAC (1.063, 0.430, 0.731 and 1.115, respectively). Docking studies with caspase-3 revealed that most of the tested compounds showed good binding with the enzyme especially for compound 6d make several interactions better than that of the reference NAC.

Production of Poly--Glutamate (PGA) Biopolymer by Batch and Semicontinuous Cultures of Immobilized Bacilluslicheniformis strain-R

Production of Polyglutamate (PGA) biopolymer by immobilized Bacilluslicheniformis strain-R was intensively investigated. Preliminary experiments were carried out to address the most suitable immobilization methodology. Entrapment of Bacillus cells in alginate-agar led optimal PGA production (36.75 g/l), with 1.32- and 2.18-fold increase in comparison with alginate- or K-carrageenan-immobilized cells, respectively. During semicontinuous cultivation of agar-alginate gel-cell mixture, production of PGA by 10 ml mixture was increased from 2nd to 3rd run whereas, increased till the 4th run using 15ml mixture. Adsorption was the most suitable immobilization technique for production of PGA and the sponge cubes was the preferred matrix recording 43.2 g/l of PGA with the highest cell adsorption. Furthermore, no PGA was detected when B. licheniformis cells were adsorbed on wood and pumice. Although luffa pulp-adsorbed cells recorded the highest PGA production (50.4 g/l), cell adsorption was the lowest. Semicontinuous cultivation of B. licheniformis cells adsorbed on sponge led to increase of PGA production till the 3rd run and reached 55.5 g/l then slightly decreased in the 4th run. The successful use of fixed-bed bioreactor for semicontinuous cultivation of B. licheniformis cells held on sponge cubes (3 runs, 96 hours/run) provides insight for the potential biotechnological production of PGA by immobilized cells.

Production of poly-gama-glutamate (PGA) biopolymer by batch and semicontinuous cultures of immobilized Bacilluslicheniformis strain-R

Production of Polyglutamate (PGA) biopolymer by immobilized Bacilluslicheniformis strain-R was intensively investigated. Preliminary experiments were carried out to address the most suitable immobilization methodology. Entrapment of Bacillus cells in alginate-agar led optimal PGA production (36.75 g/l), with 1.32- and 2.18-fold increase in comparison with alginate- or K-carrageenan-immobilized cells, respectively. During semicontinuous cultivation of agar-alginate gel-cell mixture, production of PGA by 10 ml mixture was increased from 2nd to 3rd run whereas, increased till the 4th run using 15ml mixture. Adsorption was the most suitable immobilization technique for production of PGA and the sponge cubes was the preferred matrix recording 43.2 g/l of PGA with the highest cell adsorption. Furthermore, no PGA was detected when B. licheniformis cells were adsorbed on wood and pumice. Although luffa pulp-adsorbed cells recorded the highest PGA production (50.4 g/l), cell adsorption was the lowest. Semicontinuous cultivation of B. licheniformis cells adsorbed on sponge led to increase of PGA production till the 3rd run and reached 55.5 g/l then slightly decreased in the 4th run. The successful use of fixed-bed bioreactor for semicontinuous cultivation of B. licheniformis cells held on sponge cubes (3 runs, 96 hours/run) provides insight for the potential biotechnological production of PGA by immobilized cells.

Production of Poly-γ-Glutamate (PGA) Biopolymer by Batch and Semicontinuous Cultures of Immobilized Bacilluslicheniformis strain-R.

Production of Polyglutamate (PGA) biopolymer by immobilized Bacillus licheniformis strain-R was intensively investigated. Preliminary experiments were carried out to address the most suitable immobilization methodology. Entrapment of Bacillus cells in alginate-agar led optimal PGA production (36.75 g/l), with 1.32-and 2.18-fold increase in comparison with alginate-or K-carrageenan-immobilized cells, respectively. During semicontinuous cultivation of agar-alginate gel-cell mixture, production of PGA by 10 ml mixture was increased from 2(nd) to 3(rd) run whereas, increased till the 4(th) run using 15ml mixture. Adsorption was the most suitable immobilization technique for production of PGA and the sponge cubes was the preferred matrix recording 43.2 g/l of PGA with the highest cell adsorption. Furthermore, no PGA was detected when B. licheniformis cells were adsorbed on wood and pumice. Although luffa pulp-adsorbed cells recorded the highest PGA production (50.4 g/l), cell adsorption was the lowest. Semicontinuous cultivation of B. licheniformis cells adsorbed on sponge led to increase of PGA production till the 3(rd) run and reached 55.5 g/l then slightly decreased in the 4(th) run. The successful use of fixed-bed bioreactor for semicontinuous cultivation of B. licheniformis cells held on sponge cubes (3 runs, 96 hours/run) provides insight for the potential biotechnological production of PGA by immobilized cells.