Impact of liposomal hesperetin in broilers: prospects for improving performance, antioxidant potential, immunity, and resistance against Listeria monocytogenes.

Liposomal encapsulated phytogenics, such as liposomal hesperetin, are considered novel substitutes for antibiotics in the broiler industry owing to their improved nutritional and therapeutic properties. Therefore, our key goal was to investigate liposomal hesperetin impact on broiler growth performance, health, antioxidant status, tight junction proteins (TJP), and resistance against Listeria monocytogenes. Four broiler groups were fed 0, 150, 250, or 400 mg/kg of liposomal hesperetin-supplemented diets and experimentally infected with L. monocytogenes strain. Herein, liposomal hesperetin, especially at higher concentrations, augmented broilers FCR with upregulation of genes encoding TJP (occludin, JAM-2, MUC-2), and antioxidant attributes (GPX-1, SOD-1, CAT, HO-1, NQO1, COX2), which reflect enhancing health and welfare of broilers. Muscle antioxidant biomarkers were enhanced; meanwhile, muscle MDA, ROS, and H2O2 levels were reduced in response to 400 mg/kg of liposomal hesperetin. Liposomal hesperetin fortification reduced L. monocytogenes loads and expression levels of its virulence-related genes (flaA, hlyA, and ami). Remarkably, histopathological alterations in intestinal and brain tissues of L. monocytogenes-infected broilers were restored post-inclusion at higher levels of liposomal hesperetin, which reflects increase of the birds' resistance to L. monocytogenes infection. Transcription levels of genes encoding cytokines/chemokines (MyD88, AVBD6, CCL20, IL-1ß, IL-18), and autophagy (Bcl-2, LC3, AMPK, AKT, CHOP, Bip, p62, XBP1) were ameliorated following dietary liposomal hesperetin fortification, which suggests enhancement of the birds' immunity and health. Collectively, our research recommends liposomal hesperetin application in broiler diets owing to its promoting impact on growth performance, antioxidant status, immunity, health, and welfare besides its antibacterial, and antivirulence characteristics to fight against L. monocytogenes.

Exploring the Interactive Impacts of Citronellol, Thymol, and Trans-Cinnamaldehyde in Broilers: Moving towards an Improved Performance, Immunity, Gastrointestinal Integrity, and Clostridium perfringens Resistance.

AIMS: This study aimed to explore the effectiveness of dietary citronellol, thymol, and trans-cinnamaldehyde (CTC) essential oils blend on broilers` growth performance, immunity, intestinal microbial count, gut integrity, and resistance against Clostridium perfringens utilizing the necrotic enteritis (NE) challenge model. METHODS AND RESULTS: A total of 200 Ross 308 male broiler chicks received either a control diet or diet supplemented with three graded levels of CTC blend including 300, 600, and 900 mg of CTC blend/Kg diet and experimentally infected with C. perfringens strain at 23 days of age. Herein, dietary CTC blend fortifications significantly improved the broilers` growth performance, which was supported by upregulating the expression levels of MUC-2, occludin, and JAM-2 genes. Moreover, dietary CTC blend inclusion significantly enhanced the levels of blood phagocytic percentage and serum IgA, IgG, and MPO, and reduced the values of serum CRP, and NO at 5 days pre-infection, 10-, and 15 days post-infection (dpi) with C. perfringens. At 15 dpi, CTC blend inclusion significantly reduced the intestinal digesta pH, coliforms and C. perfringens loads, and the expression levels of genes related to C. perfringens virulence (cpe, cnaA, and nanI), proinflammatory cytokines (IL-1ß and TNF-α), and chemokines (CCL20), in addition to increasing the count of beneficial total Lactobacillus and total aerobic bacteria, and the expression levels of genes related to anti-inflammatory cytokines (IL-10) and chemokines (AvBD6, and AvBD612). CONCLUSION: Our results point to the growth-provoking, immunostimulant, antibacterial, anti-inflammatory, and antivirulence characteristics of the CTC blend, which improves the broilers' resistance to C. perfringens and ameliorates the negative impacts of NE.

Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200/BMP4/Olig-2 signaling.

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig-2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig-2 positive cells count in hippocampi of chronic stress-exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig-2 proteins. This work underscores the amelioration of the stress-induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.

Enhancement of Vitamin C's Protective Effect against Thimerosal-Induced Neurotoxicity in the Cerebral Cortex of Wistar Albino Rats: An In Vivo and Computational Study.

Vitamin C was examined to ameliorate the neurotoxicity of thimerosal (THIM) in an animal model (Wistar albino rats). In our work, oxidative and antioxidative biomarkers such as SOD, LPO, and GSH were investigated at various doses of THIM with or without concurrent vitamin C administration. Furthermore, the adverse effects of THIM on hepatic tissue and cerebral cortex morphology were examined in the absence or presence of associated vitamin C administration. Also, we studied the effect of vitamin C on the metallothionein isoforms (MT-1, MT-2, and MT-3) in silico and in vivo using the RT-PCR assay. The results showed that the antioxidant biomarker was reduced as the THIM dose was raised and vice versa. THIM-associated vitamin C reduced the adverse effects of the THIM dose. The computation studies demonstrated that vitamin C has a lower ΔG of -4.9 kcal/mol compared to -4.1 kcal/mol for THIM to bind to the MT-2 protein, which demonstrated that vitamin C has a greater ability to bind with MT-2 than THIM. This is due to multiple hydrogen bonds that exist between vitamin C and MT-2 residues Lys31, Gln23, Cys24, and Cys29, and the sodium ion represents key stabilizing interactions. Hydrogen bonds involve electrostatic interactions between hydrogen atom donors (e.g., hydroxyl groups) and acceptors (e.g., carbonyl oxygens). The distances between heavy atoms are typically 2.5-3.5 Å. H-bonds provide directed, high-affinity interactions to anchor the ligand to the binding site. The five H-bonds formed by vitamin C allow it to form a stable complex with MT, while THIM can form two H-bonds with Gln23 and Cys24. This provides less stabilization in the binding pocket, contributing to the lower affinity compared to vitamin C. The histopathological morphologies in hepatic tissue displayed an expansion in the portal tract and the hepatocytes surrounding the portal tract, including apoptosis, binucleation, and karyomegaly. The histopathological morphologies in the brain tissue revealed a significant decrease in the number of Purkinje cells due to THIM toxicity. Interestingly, THIM toxicity was associated with hemorrhage and astrogliosis. Both intracellular and vasogenic edema appeared as the concentrations of THIM rose. Finally, vitamin C ameliorated the adverse effect on the cerebral cortex in Wistar albino rats.

Antibacterial biofilm efficacy of calcium hydroxide loaded on Gum Arabic nanocarrier: an in-vitro study.

BACKGROUND: An innovative intracanal medication formulation was introduced in the current study to improve the calcium hydroxide (Ca(OH)2) therapeutic capability against resistant Enterococcus faecalis (E. faecalis) biofilm. This in-vitro study aimed to prepare, characterize, and evaluate the antibacterial efficiency of Ca(OH)2 loaded on Gum Arabic (GA) nanocarrier (Ca(OH)2-GA NPs) and to compare this efficiency with conventional Ca(OH)2, Ca(OH)2 nanoparticles (NPs), GA, and GA NPs. MATERIALS AND METHODS: The prepared nanoparticle formulations for the tested medications were characterized using Transmission Electron Microscope (TEM) and Fourier-Transform Infrared Spectroscopy (FTIR). 141 human mandibular premolars were selected, and their root canals were prepared. Twenty-one roots were then sectioned into 42 tooth slices. All prepared root canals (n = 120) and teeth slices (n = 42) were divided into six groups according to the intracanal medication used. E. faecalis was inoculated in the samples for 21 days to form biofilms, and then the corresponding medications were applied for 7 days. After medication application, the residual E. faecalis bacteria were assessed using CFU, Q-PCR, and SEM. Additionally, the effect of Ca(OH)2-GA NPs on E. faecalis biofilm genes (agg, ace, and efaA) was investigated using RT-PCR. Data were statistically analyzed at a 0.05 level of significance. RESULTS: The synthesis of NPs was confirmed using TEM. The results of the FTIR proved that the Ca(OH)2 was successfully encapsulated in the GA NPs. Ca(OH)2-GA NPs caused a significant reduction in the E. faecalis biofilm gene expression when compared to the control (p < 0.001). There were significant differences in the E. faecalis CFU mean count and CT mean values between the tested groups (p < 0.001) except between the Ca(OH)2 and GA CFU mean count. Ca(OH)2-GA NPs showed the least statistical E. faecalis mean count among other groups. SEM observation showed that E. faecalis biofilm was diminished in all treatment groups, especially in the Ca(OH)2-GA NPS group when compared to the control group. CONCLUSIONS: Ca(OH)2 and GA nanoparticles demonstrate superior anti-E. faecalis activity when compared to their conventional counterparts. Ca(OH)2-GA NPs showed the best antibacterial efficacy in treating E. faecalis biofilm. The tested NP formulations could be considered as promising intracanal medications.

Neurobehavioral, biochemical and histological assessment of the effects of resveratrol on cuprizone-induced demyelination in mice: role of autophagy modulation

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol. (AU)

Radiographic and immuno-histochemical evaluation of root perforation repair using MTA with or without platelet-rich fibrin or concentrated growth factors as an internal matrix in dog's teeth: in vivo animal study.

OBJECTIVES: To comparatively evaluate the in vivo outcome of MTA repair for contaminated and non-contaminated furcation perforations (FP) with or without PRF and CGF as a matrix in dogs' teeth. METHODS: Ninety dog teeth were divided into five groups based on the iatrogenic FP repair approach after doing root canal treatment: negative control (without FP), positive control (FP without repair), MTA, MTA + PRF and MTA + CGF groups, where FP were repaired promptly in subdivision 1 (n = 10; non-contaminated) and after 4 weeks of oral contamination in subdivision 2 (n = 10;contaminated). After 3 months, the perforation site was assessed radiographically (vertical bone density), histologically (inflammatory cell count, epithelial proliferation, cementum and bone deposition) and immunohistochemically (OPN and TRAP antibodies localisation). Data collected were statistically analysed using SPSS software at a 0.05 significance level. RESULTS: The MTA + PRF and MTA + CGF groups demonstrated significantly more bone formation, OPN immunolocalisation and fewer inflammatory cell counts than MTA group. MTA, MTA + PRF and MTA + CGF groups showed significantly favourable radiographic, histological and immunohistochemical healing features than the positive control, especially in non-contaminated subdivisions, that significantly showed better features than the contaminated subdivisions (P < 0.001). CONCLUSION: The use CGF and PRF as a matrix beneath MTA in FP repair in dog's teeth is promising as it could increase hard and soft tissue regeneration in non-contaminated and contaminated perforations. CLINICAL RELEVANCE: The repair of FP is challenging especially when associated with contaminated inter-radicular bone loss. Radiographic, histological and immunohistochemical comprehensive evaluation of the root and surrounding attachment apparatus response to different perforation repair protocols could give a predictable clinical outcome.

Neurobehavioral, biochemical and histological assessment of the effects of resveratrol on cuprizone-induced demyelination in mice: role of autophagy modulation.

Resveratrol is known to exhibit neuroprotective effects in many neurological disorders via autophagy modulation. However, controversial results have been reported about the therapeutic potential of resveratrol and the implication of autophagy in demyelinating diseases. This study aimed to evaluate the autophagic changes in cuprizone-intoxicated C57Bl/6 mice and explore the effect of autophagy activation by resveratrol on the demyelination and remyelination processes. Mice were fed with chow containing 0.2% cuprizone for 5 weeks, followed by a cuprizone-free diet for 2 weeks. Resveratrol (250 mg/kg/day) and/or chloroquine (an autophagy inhibitor; 10 mg/kg/day) were given for 5 weeks starting from the third week. At the end of the experiment, animals were tested on rotarod and then sacrificed for biochemical assessment, luxol fast blue (LFB) staining, and transmission electron microscopy (TEM) imaging of the corpus callosum. We observed that cuprizone-induced demyelination was associated with impaired degradation of autophagic cargo, induction of apoptosis, and manifest neurobehavioral disturbances. Oral treatment with resveratrol promoted motor coordination and improved remyelination with regular compacted myelin in most axons without a significant impact on myelin basic protein (MBP) mRNA expression. These effects are mediated, at least in part, via activating autophagic pathways that may involve SIRT1/FoxO1 activation. This study verified that resveratrol dampens cuprizone-induced demyelination, and partially enhances myelin repair through modulation of the autophagic flux, since interruption of the autophagic machinery by chloroquine reversed the therapeutic potential of resveratrol.

Is Survival with Conservative Breast Therapy Becoming Superior to That with Modified Radical Mastectomy Alone for the Treatment of Early Breast Cancer in This Era?

This study aims to assess survival rates in early breast cancer patients treated by conservative breast therapy (CBT), including radiotherapy, compared with those treated by modified radical mastectomy (MRM) alone. The South Egypt Cancer Institute and the Assiut University Oncology Department patients' records, from January 2010 to December 2017, were searched for T1-2N0-1M0 breast cancer patients treated by CBT or MRM. Patients who did not receive chemotherapy were excluded to reduce the treatment variation. The 5-year locoregional disease-free survival (LRDFS) was 97.3% for the CBT patients was and 98.0% for the MRM patients (P = .675). The 5-year distant disease-free survival (DDFS) was 93.6% for CBS and 85.7% for MRM (P = 0.033). The DFS was 91.9% for the BCT patients and 85.3% for the MRM patients (P = 0.045). The 5-year OS was 98.2% for the CBT patients and 94.3% for the MRM patients, (P = 0.02). By Cox regression analysis, the CBT resulted in significantly better OS, (P = 0.018) and the HR = 0.350, 95% CI 0.146-0.837. The adjusted OS, estimated by the propensity score-based weights, remained superior in CBT than in MRM patients (P < 0.001). CBT resulted in better DDFS, DFS, and OS than MRM. Future randomized trials are needed to confirm these findings and determine the cause.

Evaluation of Systemic Antifungal Prescribing Knowledge and Practice in the Critical Care Setting among ICU Physicians and Clinical Pharmacists: A Cross-Sectional Study.

Management of invasive fungal infections (IFI) and subsequent treatment choices remain challenging for physicians in the ICU. Documented evidence shows increased practice of the inappropriate use of antifungal agents in the ICU. Continuous education of healthcare providers (HCPs) represents the cornerstone requirement for starting an antifungal stewardship program (AFS). This study aimed at evaluating knowledge gaps in systemic antifungal prescribing among physicians and clinical pharmacists in a critical care setting. A cross-sectional, multi-center, survey-based study was conducted in five tertiary hospitals located in Al-Ahsaa, Saudi Arabia between January and May 2021. A self-administered questionnaire was distributed among the targeted clinicians. A total of 63 clinicians were involved (65.5% ICU physicians and 34.5% clinical pharmacists). It was noted that a minority of the participating HCPs (3.2%) had overall good knowledge about antifungal prescribing, but the majority had either moderate (46%) or poor (50.8%) knowledge. The difference in overall knowledge scores between the ICU physicians and the clinical pharmacists (p = 0.925) was not significant. However, pharmacists showed better scores for the pharmacokinetics of antifungal therapy (p = 0.05). This study has revealed a significant gap in the knowledge and practice of clinicians as regards prescribing antifungal therapy in our area. Although the results cannot be generalized, the outcome of this study has exposed the need for a tailored training program essential for carrying out an AFS program.

Amelioration effect of 18ß-Glycyrrhetinic acid on methylation inhibitors in hepatocarcinogenesis -induced by diethylnitrosamine.

Aim: suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid. Method: In the current work, we investigated the effect of sole GA combined with different agents such as doxorubicin (DOX) or probiotic bacteria (Lactobacillus rhamanosus) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue. Results: Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively. Conclusion: GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.

Predictors of peritoneal metastasis of gastric origin.

BACKGROUND: Gastric adenocarcinoma is one of the most aggressive forms of cancer. Despite marked advancements in radiological techniques, peritoneal deposits are still only discovered during laparotomies in a significant number of cases. The role of surgery in the management of metastatic gastric cancer is very limited, reducing the value of conducting laparotomies. In addition, conducting laparoscopies for the purposes of properly staging every case of gastric cancer is difficult, especially in healthcare systems with limited resources. It is thus crucial to investigate all possible predictors of peritoneal metastasis of gastric cancer, with the aim of reserving the use of laparoscopies to cases known to have high incidences of peritoneal metastasis despite negative radiological results. PATIENTS AND METHODS: This is a case control study that included all cases of gastric adenocarcinoma that had presented to the National Cancer Institute-Cairo University between January 2018 and December 2019. The 'cases' group encompassed all gastric adenocarcinoma patients who were found to have peritoneal metastasis, whilst the 'control' group included those patients who were apparently metastasis-free. Comparisons were made between the two groups in terms of demographics, tumor characteristics, and results of laboratory tumor marker investigations. RESULTS: Patients with peritoneal metastasis were statistically significantly younger than those who had no apparent metastasis (mean ± SD 51.4 ± 12.5 and 56.2 ± 12.6 respectively; P = 0.020). Significant associations were found between a finding of peritoneal metastasis and (i) a middle tumor site (P = 0.002); (ii) tumor thickening morphology (P < 0.001); (iii) undifferentiated histopathology (P = 0.040); (iv) tumor grade III (P < 0.001); (v) lower lymphocyte counts of < 1.9/ml (P = 0.030); and (vi) high levels of CA 19-9 of > 37 units/ml (P = 0.032). CONCLUSION: Tumor pathological criteria, including tumor site, degree of differentiation, shape, and grading, as well as laboratory findings of low lymphocytic counts and high levels of CA 19-9 appear to be reliable predictors of the presence of peritoneal metastasis from a gastric adenocarcinoma.

Impact of Omega-3 Fatty Acids Nano-Formulation on Growth, Antioxidant Potential, Fillet Quality, Immunity, Autophagy-Related Genes and Aeromonas hydrophila Resistance in Nile Tilapia (Oreochromis niloticus).

In modern aquaculture, enriching Nile tilapia's diet with omega-3 poly-unsaturated fatty acids (PUFAs) not only plays an important role in its general health but also fortifies its fillet with omega-3-PUFAs. However, the major challenge affecting their delivery is their high instability due to oxidative deterioration. Thus, the prospective incorporation of omega-3-PUFAs into nanocarriers can enhance their stability and bioactivity. In this regard, the effect of reformulated omega-3-NPs was investigated on Nile tilapia's performance, flesh antioxidant stability, immunity, and disease resistance. Four fish groups supplemented with omega-3-PUFAs-loaded nanoparticles (omega-3 NPs) at levels of 0, 1, 2, and 3 g/kg diet and at the end of feeding trial fish challenged with Aeromonas hydrophila. Fish performance (weight gain and feed conversion) was improved in groups supplemented with omega-3-NPs (2 and 3 g/kg diet). The deposition of omega-3-PUFAs in fish flesh elevated with increasing dietary omega-3-NPs. Simultaneously the oxidative markers (H2O2, MDA, and reactive oxygen species) in fish flesh were reduced, especially with higher omega-3-NPs. Post-challenge, downregulation of IL-1ß, IL-6, IL-8, TNF-α, and caspase-1 were noticed after dietary supplementation of omega-3-NPs. Moreover, mRNA expression of autophagy-related genes was upregulated while the mTOR gene was downregulated with higher omega-3 NPs levels. Lower expression of A. hydrophila ahyI and ahyR genes were detected with omega-3 NPs supplementation. In conclusion, omega-3-NPs application can fortify tilapia flesh with omega-3-PUFAs and augment its performance, immunity, and disease resistance against Aeromonas hydrophila.

Dietary Eugenol Nanoemulsion Potentiated Performance of Broiler Chickens: Orchestration of Digestive Enzymes, Intestinal Barrier Functions and Cytokines Related Gene Expression With a Consequence of Attenuating the Severity of E. coli O78 Infection.

Recently, the use of essential oils (EOs) or their bioactive compounds encapsulated by nanoparticles as alternative supplements for in-feed antimicrobials is gaining attention, especially in organic poultry production. Focusing on eugenol, its incorporation into the nanoformulation is a novel strategy to improve its stability and bioavailability and thus augment its growth-boosting and antimicrobial activities. Therefore, we explored eugenol nanoemulsion activities in modulating growth, digestive and gut barrier functions, immunity, cecal microbiota, and broilers response to avian pathogenic E. coli challenge (APEC) O78. A total of 1,000 one-day-old broiler chicks were allocated into five groups; negative control (NC, fed basal diet), positive control (PC), and 100, 250, and 400 mg/kg eugenol nanoemulsion supplemented groups. All groups except NC were challenged with APEC O78 at 14 days of age. The results showed that birds fed eugenol nanoemulsion displayed higher BWG, FI, and survivability and most improved FCR over the whole rearing period. Birds fed 400 mg/kg of eugenol nanoemulsion sustained a higher growth rate (24% vs. PC) after infection. Likely, the expression of digestive enzymes' genes (AMY2A, CCK, CELA1, and PNLIP) was more prominently upregulated and unaffected by APEC O78 challenge in the group fed eugenol nanoemulsion at the level of 400 mg/kg. Enhanced gut barrier integrity was sustained post-challenge in the group supplemented with higher levels of eugenol nanoemulsion as evidenced by the overexpression of cathelicidins-2, ß-defensin-1, MUC-2, JAM-2, occludin, CLDN-1, and FABP-2 genes. A distinct modulatory effect of dietary eugenol nanoemulsion was observed on cytokine genes (IL-1ß, TNF-α, IL-6, IL-8, and IL-10) expression with a prominent reduction in the excessive inflammatory reactions post-challenge. Supplementing eugenol nanoemulsion increased the relative cecal abundance of Lactobacillus species and reduced Enterobacteriaceae and Bacteriods counts. Notably, a prominent reduction in APEC O78 loads with downregulation of papC, iroN, iutA, and iss virulence genes and detrimental modifications in E. coli morphological features were noticed in the 400 mg/kg eugenol nanoemulsion group at the 3rd-week post-challenge. Collectively, we recommend the use of eugenol nanoemulsion as a prospective targeted delivery approach for achieving maximum broilers growth and protection against APEC O78 infection.

Comparative evaluation of the antibacterial effect of Allium sativum, calcium hydroxide and their combination as intracanal medicaments in infected mature anterior teeth: A randomized clinical trial.

AIM: The purpose of this study was to compare the antibacterial effects of Allium sativum (garlic extract), calcium hydroxide (Ca [OH]2 ) and their combination as intracanal medicaments in infected mature anterior teeth using real-time PCR. METHODOLOGY: This prospective double-blind, controlled, parallel, superiority, randomized clinical trial was carried out on 66 permanent, necrotic incisors associated with asymptomatic apical periodontitis in 66 male patients. Patients were randomly divided into three groups (n = 22) according to the intracanal medications used. After access preparation, four microbiological samples (S) were taken using sterile absorbent paper points as follows: S1: before canal instrumentation and S2: after cleaning and shaping. The third sample (S3) and fourth sample (S4) were taken after the placement of the tested intracanal medications into their corresponding canals for 7 and 14 days, respectively. Total DNA was extracted from microbiological samples and relative quantitative real-time PCRs were done to quantify the relative gene expression fold change (FC) for Enterococcus faecalis and Streptococcus species. At significance level p ≤ .05, the data were statistically analysed in SPSS software using Kruskal-Wallis and Freidman's tests, followed by Dunn-Bonferroni post hoc test for pairwise comparisons. RESULTS: Both bacterial mean FC decreased significantly after mechanical instrumentation (S1 to S2) in all groups. However, no statistically significant differences were found after intracanal medicament placement (from S2 to S3 and from S3 to S4) except in the garlic group. Garlic significantly reduced Enterococcus faecalis FC in S3 and S4 when compared to Ca (OH)2 and Ca (OH)2 + garlic combination. However, garlic and Ca (OH)2 reduced Streptococcus bacteria in S3 similarly. Whilst in S4, garlic showed significantly more reduction than Ca (OH)2 . The combination of Ca (OH)2 with garlic extract showed the least significant bacterial reduction. CONCLUSION: Within the study limitations, garlic intracanal medicament has a comparable anti-Streptococcus efficiency to Ca (OH)2 , whilst it is more effective against Enterococcus faecalis species. When Ca (OH)2 and garlic are combined, their antibacterial effectiveness is reduced. Increasing the time of application for tested intracanal medicaments by more than one week has no additional antibacterial effectiveness.

Evaluation of new bioceramic endodontic sealers: An in vitro study.

BACKGROUND: The biophysical properties of root canal sealers (RCSs) positively affect the success of endodontic treatment. It is important to ensure an impermeable apical seal after the thorough eradication of the infection. Since bioceramic sealers release bioactive and concomitantly biocompatible products after setting, chemical bonding to dentin and favorable healing is achieved. OBJECTIVES: This study evaluated the chemical composition and elemental distribution of 4 RCSs (1 resinbased and 3 bioceramic-based) by using energy dispersive X-ray spectroscopy (EDX), field emission scanning electron microscopy (FE-SEM) and elemental mapping after root canal obturation, both coronally and apically. MATERIAL AND METHODS: Forty extracted single-rooted teeth were shaped, cleaned and randomly divided into 4 groups according to the type of sealer used for obturation. After the sealer set, the teeth were sectioned horizontally to obtain coronal and apical standardized sections. The sections were qualitatively and quantitatively assessed in terms of chemical composition of the tested sealers, using SEM images and elemental mapping as well as the EDX analysis. RESULTS: All of the calcium silicate sealers showed significantly higher peaks of calcium at the periphery of the root canals, contacting dentinal moisture, and high peaks of zirconium, while tungsten was significantly high in AH Plus™. TotalFill® BC™ and BioRoot™ RCS showed higher calcium, oxygen and silicon content coronally than apically, while phosphorus was only detected more apically, which was different for EndoSeal® MTA. All sealers revealed small amounts of different heavy metals, not described by their manufacturers, and a uniform particle distribution with almost regular surfaces. CONCLUSIONS: All of the tested sealers except AH Plus revealed high calcium/phosphorus ratio peaks, suggesting regenerative potential in vivo, with acceptable purity and surface texture, and supporting their biocompatibility, with chemical bonding to root dentin.

Overexpression of PD-1 and CD39 in tumor-infiltrating lymphocytes compared with peripheral blood lymphocytes in triple-negative breast cancer.

BACKGROUND AND AIM: Growing evidence highlighted the primary role of the immune system in the disease course of triple-negative breast cancer (TNBC). The study aim was to investigate the expression of PD-1 and CD39 on CD4+ and CD8+ cells infiltrating tumor tissue compared to their counterparts in peripheral blood and explore its association with tumor characteristics, disease progression, and prognosis in females with TNBC. PATIENTS AND METHODS: The study included 30 TNBC patients and 20 healthy controls. Cancer and normal breast tissue and peripheral blood samples were collected for evaluation of the expression of PD-1 and CD39 on CD4+ and CD8+T cells by flow cytometry. RESULTS: A marked reduction in the percentage of CD8+ T lymphocytes and a significant increase in the frequencies of CD4+ T lymphocytes and CD4+ and CD8+ T lymphocytes expressing PD1 and CD39 were evident in tumor tissue in comparison with the normal breast tissue. The DFS was inversely related to the cancer tissue PD1+CD8+ and CD39+CD8+ T lymphocytes. Almost all studied cells were significantly increased in the tumor tissue than in peripheral blood. Positive correlations were detected among peripheral PD1+CD4+T lymphocytes and each of cancer tissue PD1+CD4+, PD1+CD8+and CD39+CD8+T cells, and among peripheral and cancer tissue CD39+CD4+and CD39+CD8+ T cells. CONCLUSIONS: The CD39 and PD1 inhibitory pathways are synergistically utilized by TNBC cells to evade host immune response causing poor survival. Hence, combinational immunotherapy blocking these pathways might be a promising treatment strategy in this type of cancer.

Apoptotic protease activating factor-1 gene and MicroRNA-484: A possible interplay in relapsing remitting multiple sclerosis.

BACKGROUND: Emerging evidence suggests that dysregulated apoptosis might be implicated in the pathogenesis of multiple sclerosis (MS). The aim of the current study was to evaluate the expression of Apoptotic protease activating factor-1 (APAF1) mRNA and its potential regulator miR-484 in relapsing remitting MS patients (RRMS) and to investigate their role as potential disease biomarkers. METHODS: After Bioinformatic analysis was conducted and revealed miR-484 involvement in the regulation of APAF-1 gene expression. Reverse Transcription-quantitative Real-Time PCR (RT-qPCR) was performed to detect the expression levels of APAF-1 and miR-484 in the peripheral blood mononuclear cells (PBMCs) of 34 RRMS patients recruited from the MS clinic of kasr al ainy hospital- faculty of medicine-Egypt and 34 healthy controls. RESULTS: APAF-1 mRNA was significantly downregulated in patients whereas miR-484 expression was upregulated compared to controls (p < 0.01). Sensitivity and specificity of APAF-1 and miR-484 to diagnose MS was (85.3%, 76.5%) and (88.2% and 86.7%) respectively. CONCLUSION: APAF-1 and miR-484 could play a role as potential MS diagnostic biomarkers. However, absence of a control group of patients with other inflammatory diseases in our study warrants further research to corroborate our findings.

Bioactives of Pomegranate By-Products and Barley Malt Grass Engage in Cereal Composite Bar to Achieve Antimycotic and Anti-Aflatoxigenic Attributes.

Food is the source from where a person obtains the body's daily requirements. People's current daily habits force them to consume fast food, which is known for its poor nutritional and safety features. So, it is urgent to provide a suitable substitution product to solve this issue. The present investigation aimed to produce a bar with a dual function: nutritional and long shelf life. Two materials were chosen to support the bar manufacturing regarding their bioactive contents, barley malt grass (BMG) and pomegranate byproducts (PBD). Chemical composition, antioxidant, and antimicrobial potency were measured. Β-carotene, vitamin C, and tocopherol were determined using HPLC apparatus. Extracts' bio-safety against cell lines was determined, besides their enhancement against cell-death factors. Simulation experiments were designed to evaluate extracts' impact to extend bar shelf life. Data represented the richness of essential minerals and fibers. Results of the FTIR reflected the existence of various active groups in the contents. Phenolic fractions of PBD are distinctive for their content of ellagic (39.21 ± 5.42 mg/kg), ferulic acid fractions (31.28 ± 4.07 mg/kg) which is a known with antifungal activity. Extracts and their mix (1:1) represented inhibition zone diameters that reach 15.1 ± 1.66 mm for bacteria and 23.81 ± 1.41 mm for fungi. Extracts were shown to have better safety against the cell line strain of hepatic HL-7702, with an elevation of a harmful dose of aflatoxin (IC50 304.5 µg/mL for PBD, IC50 381 µg/mL for BMG). Sensory evaluation of fortified bars reflected a preferable application of mix (1:1) due to color attributes and panelist evaluations, the same result recorded for simulation studies. The experiment recommended applying a mix (1:1) of BMG: PBD in addition to their extracts (200 mg/kg dough) for functional bar manufacturing with antifungal properties.