Efficacy of silver nanoparticles against Trichinella spiralis in mice and the role of multivitamin in alleviating its toxicity.

Trichinellosis is a worldwide zoonotic disease. The majority of currently available anti-trichinellosis medications exhibit inadequate efficacy. The efficacy of a natively prepared new formulation of silver nanoparticles (Ag-NPs) was evaluated in the treatment of Trichinella spiralis (T. spiralis) infection in mice alone and combined with multivitamin-mineral (MM). After investigating the product's biological and pharmacological characteristics, its therapeutic dose was estimated to be Ag-NPs at 21.5 mg/kg B.W. This dose was orally inoculated to experimentally infected mice at 3-5 days post-inoculation (dpi) against the mature worms, at 8-10 dpi against the newborn larvae, and at 33-35th dpi against the encapsulated larvae. Each treatment's efficacy was assessed by scarifying control and treated mice 3 days post-treatment. The drug alone or in supplement form has a high trichinocidal effect exceeding that of the reference drug. Early treatment (3-5 dpi) by Ag-NPs or Ag-NPs + MM and albendazole revealed high efficacy against the intestinal stage, reaching 93.3%, 94.7%, and 90.6% for the three treatments, respectively. The materials causing a significant (P-value < 0.001) decrease in the mean encapsulated larvae reached 86.61%, 89.07%, and 88.84%/gm of muscles using the three treatments, respectively. Moreover, all larvae extracted from Ag-NPs-treated groups failed to induce infection post-inoculation in new mice. Additionally, combining the material with MM proved to overcome the reversible adverse effects of silver material on the estimated redox parameters and liver and kidney biomarkers, denoting its ability to alleviate Ag-NP toxicity. In conclusion, the high trichinocidal effect of Ag-NPs against the adult and encapsulated larvae during a short inoculation period introduced Ag-NPs as an alternative to other nematicidal drugs.

FolE gene expression for folic acid productivity from optimized and characterized probiotic Lactobacillus delbrueckii.

BACKGROUND: Lactobacillus delbrueckii was one of the most common milk lactic acid bacterial strains (LAB) which characterized as probiotic with many health influencing properties. RESULTS: Among seven isolates, KH1 isolate was the best producer of folic acid with 100 µg/ml after 48 h of incubation; FolE gene expression after 24 h of incubation was in the highest value in case of KH1 with three folds. Lactose was the best carbon source for this KH1, besides the best next isolates KH80 and KH98. The selected three LAB isolates were identified through 16S rDNA as Lactobacillus delbrueckii. These three isolates have high tolerance against acidic pH 2-3; they give 45, 10, and 22 CFUs at pH 3, besides 9, 6, and 4 CFUs at pH2, respectively. They also have resistance against elevated bile salt range 0.1-0.4%. KH1 recorded 99% scavenging against 97.3% 1000 µg/ml ascorbic acid. Docking study exhibits the binding mode of folic acid which exhibited an energy binding of - 8.65 kcal/mol against DHFR. Folic acid formed four Pi-alkyl, Pi-Pi, and Pi-sigma interactions with Ala9, Ile7, Phe34, and Ile60. Additionally, folic acid interacted with Glu30 and Asn64 by three hydrogen bonds with 1.77, 1.76, and 1.96 Å. CONCLUSION: LAB isolates have probiotic properties, antioxidant activity, and desired organic natural source for folic acid supplementation that improve hemoglobin that indicated by docking study interaction.

Improved Metastasis- and Disease-Free Survival With Preoperative Sequential Short-Course Radiation Therapy and FOLFOX Chemotherapy for Rectal Cancer Compared With Neoadjuvant Long-Course Chemoradiotherapy: Results of a Matched Pair Analysis.

PURPOSE: To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. METHODS AND MATERIALS: Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). CONCLUSIONS: Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.