Leverage of Salvadora persica and Pulicaria undulata extracts in Escherichia coli-challenged broiler chickens.

Escherichia coli (E. coli) is a significant challenge in the poultry industry due to their related use of antimicrobial compounds and the drastic losses in production and livability. This study investigated the preventive impacts of dietary supplementation of Salvadora persica (SP) and/or Pulicaria undulata (PU) extracts on growth traits, biochemical and immune parameters, and related gene expression of E. coli-infected broilers. A total of 120 one-day-old Cobb broilers were used. The chicks were allocated into eight equal groups (3 replicates/ group; 5 chicks per each replicate) as follows: G1; control negative, G2; SP-treated, G3; PU-treated, G4; SP/PU-treated, G5; E. coli infected, G6; E. coli infected and SP-treated, G7; E. coli infected and PU-treated, G8; E. coli infected and SP/PU-treated groups. Results revealed significant improvement in average body weight (ABW), average weight gain (AWG) and feed conversion ratio (FCR) in broilers fed diets supplemented with SP and/or PU compared to control and E. coli infected groups. Moreover, significant (P < 0.05) reduction in ALT, AST, creatinine, and uric acid was reported in other treated groups compared to the single E. coli-infected broilers. On the contrary, a significant increase (P < 0.05) in serum immunoglobulin and protein concentration was also reported in treated groups when compared to E. coli-infected untreated group. In addition, feeding broilers with SP and/or PU significantly improved (P < 0.05) the relative weight of immune-related organs and gene expression of TLR-15, with subsequent down-regulation of IL-1ß and TNF-α mRNA transcripts. Supplementing broilers with dietary SP and/or PU could be promising in the prevention of E. coli infection via stimulating significant improvement of immune-related gene expression, immune-related organ weight, and down-regulation of inflammatory-related genes, with subsequent enhancement of the growth performance of broiler chickens.

Characterizing EBV-associated Gastric Carcinoma (EBVaGC): A deep dive into LMP1 expression patterns.

Gastric cancer (GC) is a serious public health issue due to its frequency and severity. It is, for both sexes, one of the most common causes of cancer-related death and is a major contributor to the global burden of disease. Recent data show that Epstein-Barr virus (EBV) has been detected in different histopathological subtypes of gastric carcinoma and that EBV-associated gastric carcinoma (EBVaGC) represents about 10% of all cases. Moreover, the LMP1 protein characterizing the malignant transformation of cells in several cancer models seems to be very rarely expressed in this type of cancer. This study aimed to characterize EBVaGC in our population by detecting LMP1 in gastric carcinomas in about 30 selected patients. The results showed that in our population, nuclear staining predominates, showing that the antrum remains the most sampled site both for these pathologies and for LMP1 positivity (nuclear staining). In general, the LMP1 marking was negative for 22.58%, positive with a nuclear predominance at 64.52%, nuclear and cytoplasmic at 12.90%, and no positive marking for the cytoplasm. Results were not like the different studies on the expression of this oncogenic protein without EBVsCG, probably finding an explanation in the fact that our country is among the endemic regions for this herpes virus. In conclusion, the rate of LMP1 expression among gastric carcinomas does not seem similar to that observed in other countries. This study characterizing EBVaGC in Tizi-Ouzou, Algeria, reinforces the need for further studies to clarify the role of EBV (LMP1) and to explore its potential value as a predictive biomarker for the development of this type of cancer pathology.

The potential role of Epstein-Barr Virus in breast cancer development.

We are looking into viral components that may contribute to breast cancer in order to find possible therapeutic targets. The Epstein-Barr virus (EBV), which has been found to cause nasopharyngeal carcinoma and Burkitt lymphoma, is thought to play a role in breast cancer. Our series' patients had a median age of 49, with nearly half being under the age of 49. T2 tumors (two to five centimeters in size) make up the vast majority of our collection (60%). Six percent of our patients showed lymph node involvement, with roughly the same number in the N1 and N2 stages (41.17% each). Only 17.64% of people are at the N3 stage. SBR II tumors were the most common (90%). Only 20% of patients have HER2 overexpression, whereas 73.33% have ER expression. EBV was found in 23.33% of breast carcinomas (7 cases/30) after oncoprotein LMP1 expression, but normal surrounding tissues tested negative. We discovered that overexpression of the HER2 protein is inversely related to the two HRs' expression. They have no relationship with EBV infection and, consequently, LMP1 expression. LMP1 expression was not shown to be linked with patient age, tumor grade, tumor size, or lymph node invasion.

Suppression of Nasopharyngeal and Gastric Tumor Growth in a Mouse Model by Antibodies to Epstein-Barr Virus LMP1 Protein.

The study aimed to investigate the antitumor efficacy of anti-LMP1 antibodies in EBV-positive nasopharyngeal and stomach cell lines and xenograft models. The study also examined the NF-κB expression and cell cycle activation of NPC-serum-exosome-associated LMP1. Anti-LMP1 antibody treatment before or during cell implantation prevented tumor growth in nude mice. A small dose of antibodies resulted in complete tumor regression for at least three months after the tumors had grown in size. The consumption of antigen-antibody complexes by tumor cells limited tumor growth. In vitro experiments showed that anti-LMP1 antibodies killed EBV-positive NPC- or GC-derived epithelial cell lines and EBV-positive human B-cell lines but not EBV-negative cell lines. Treatment with anti-LMP1 reduced NF-κB expression in cells. The animal model experiments showed that anti-LMP1 inhibited and prevented NPC- or GC-derived tumor growth. The results suggest that LMP1 antibody immunotherapy could cure nasopharyngeal cancer, EBV-positive gastric carcinoma, and EBV-associated lymphomas. However, further validation of these findings is required through human clinical trials.

Development and Optimization of Tamarind Gum-ß-Cyclodextrin-g-Poly(Methacrylate) pH-Responsive Hydrogels for Sustained Delivery of Acyclovir.

Acyclovir has a short half-life and offers poor bioavailability. Its daily dose is 200 mg five times a day. A tamarind gum and ß-cyclodextrin-based pH-responsive hydrogel network for sustained delivery of acyclovir was developed using the free-radical polymerization technique. Developed networks were characterized by FTIR, DSC, TGA, PXRD, EDX, and SEM. The effect of varying feed ratios of polymers, monomers, and crosslinker on the gel fraction, swelling, and release was also investigated. FTIR findings confirmed the compatibility of the ingredients in a new complex polymer. The thermal stability of acyclovir was increased within the newly synthesized polymer. SEM photomicrographs confirmed the porous texture of hydrogels. The gel fraction was improved (from 90.12% to 98.12%) with increased reactant concentrations. The pH of the dissolution medium and the reactant contents affected swelling dynamics and acyclovir release from the developed carrier system. Based on the R2 value, the best-fit model was zero-order kinetics with non-Fickian diffusion as a release mechanism. The biocompatibility of the developed network was confirmed through hematology, LFT, RFT, lipid profile, and histopathological examinations. No sign of pathology, necrosis, or abrasion was observed. Thus, a pH-responsive and biocompatible polymeric system was developed for sustained delivery of acyclovir to reduce the dosing frequency and improve patient compliance.

An Improved Tobacco Mosaic Virus (TMV)-Conjugated Multiantigen Subunit Vaccine Against Respiratory Tularemia.

Francisella tularensis, the causative agent of the fatal human disease known as tularemia is classified as a Category A Select Agent by the Centers for Disease Control. No licensed vaccine is currently available for prevention of tularemia in the United States. Previously, we published that a tri-antigen tobacco mosaic virus (TMV) vaccine confers 50% protection in immunized mice against respiratory tularemia caused by F. tularensis. In this study, we refined the TMV-vaccine formulation to improve the level of protection in immunized C57BL/6 mice against respiratory tularemia. We developed a tetra-antigen vaccine by conjugating OmpA, DnaK, Tul4, and SucB proteins of Francisella to TMV. CpG was also included in the vaccine formulation as an adjuvant. Primary intranasal (i.n.) immunization followed by two booster immunizations with the tetra-antigen TMV vaccine protected 100% mice against i.n. 10LD100 challenges dose of F. tularensis live vaccine strain (LVS). Mice receiving three immunization doses of tetra-antigen TMV vaccine showed only transient body weight loss, cleared the infection rapidly, and showed minimal histopathological lesions in lungs, liver, and spleen following a lethal respiratory challenge with F. tularensis LVS. Mice immunized with the tetra-antigen TMV vaccine also induced strong ex vivo recall responses and were protected against a lethal challenge as late as 163 days post-primary immunization. Three immunization with the tetra-antigen TMV vaccine also induced a stronger humoral immune response predominated by IgG1, IgG2b, and IgG2c antibodies than mice receiving only a single or two immunizations. Remarkably, a single dose protected 40% of mice, while two doses protected 80% of mice from lethal pathogen challenge. Immunization of Interferon-gamma (IFN-γ)-deficient mice with the tetra-antigen TMV vaccine demonstrated an absolute requirement of IFN-γ for the generation of protective immune response against a lethal respiratory challenge with F. tularensis LVS. Collectively, this study further demonstrates the feasibility of TMV as an efficient platform for the delivery of multiple F. tularensis antigens and that tetra-antigen TMV vaccine formulation provides complete protection, and induces long-lasting protective and memory immune responses against respiratory tularemia caused by F. tularensis LVS.