Potential role of dietary Boswellia serrata resin against mancozeb fungicide-induced immune-antioxidant suppression, histopathological alterations, and genotoxicity in Nile tilapia, Oreochromis niloticus.

This study was established to look into the toxicological consequences of chronic exposure to a fungicide (mancozeb; MAZ) on the immune-antioxidant response, gene expressions, hepato-renal functions, and histological pictures of Nile tilapia (Oreochromis niloticus). Additionally, the effectiveness of Indian frankincense resin extract (IFRE) to mitigate their toxicity was taken into account. Fish (n =240; average body weight: 22.45 ± 2.21 g) were randomized into four groups for eight weeks in six replicates (control, IFRE, MAZ, and IFRE + MAZ), where ten fish were kept per replicate. The control and IFRE groups received basal diets that included 0.0 and 5 g/kg of IFRE without MAZ exposure. The MAZ and IFRE+MAZ groups received the same diets and were exposed to 1/10 of the 96-h of LC50 of MAZ (1.15 mg/L). The outcomes displayed that MAZ exposure resulted in a lower survival rate (56.67 %) and significantly decreased levels of immune-antioxidant variables (antiprotease, complement3, phagocytic activity, lysozyme, glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) compared to the control group. The MAZ-exposed fish showed the greatest levels of lipid peroxide (malondialdehyde), alkaline phosphatase, alanine amino-transferase, and stress indicators (cortisol and glucose). Additionally, histopathological alterations, including vacuolation, severe necrosis, degeneration, and mononuclear cell infiltrations in the hepatic, renal, and splenic tissues resulted, besides a reduction in the melanomacrophage center in the spleen. A down-regulation of immune-antioxidant-associated genes [toll-like receptors (TLR-2 and TLR-7), nuclear factor kappa beta (NF-κß), transforming growth factor-beta (TGF-ß), phosphoinositide-3-kinase regulatory subunit 3 gamma b (pik3r3b), interleukins (IL-1ß and IL-8), glutathione synthetase (GSS), glutathione peroxidase (GPx), and superoxide dismutase (SOD)] were the consequences of the MAZ exposure. Remarkably, the dietary inclusion of IFRE in MAZ-exposed fish augmented the immune-antioxidant parameters, including their associated genes, decreased stress response, and increased survival rate (85 %) compared with the MAZ-exposed fish. Moreover, dietary IFRE improved hepato-renal function indices by preserving the histological architecture of the hepatic, renal, and splenic tissues. The insights of this study advocate the use of an IFRE-dietary addition to protect Nile tilapia from MAZ toxicity, which provides perspectives for future implementations in enhancing fish health for sustainable aquaculture.

Impacts of Solid-State Fermented Barley with Fibrolytic Exogenous Enzymes on Feed Utilization, and Antioxidant Status of Broiler Chickens.

The present and future high demand of common cereals as corn and wheat encourage the development of feed processing technology that allows for the dietary inclusion of other cereals of low nutritional value in poultry feeding. Barley grains contain anti-nutritional factors that limit their dietary inclusion in the poultry industry. The treatment of barley with solid-state fermentation and exogenous enzymes (FBEs) provides a good alternative to common cereals. In this study, barley grains were subjected to solid-state microbial fermentation using Lactobacillus plantarum, Bacillus subtilis and exogenous fibrolytic enzymes. This study aimed to assess the impact of FBEs on growth, feed utilization efficiency, immune modulation, antioxidant status and the expression of intestinal barrier and nutrient transporter-related genes. One-day-old broiler chicks (Ross 308, n = 400) comprised four representative groups with ten replicates (10 chicks/replicate) and were fed corn-soybean meal basal diets with inclusions of FBEs at 0, 5, 10 and 15% for 38 days. Solid-state fermentation of barley grains with fibrolytic enzymes increased protein content, lowered crude fiber and reduced sugars compared to non-fermented barley gains. In consequence, the group fed FBEs10% had the superior feed utilization efficiency and body weight gain (increased by 4.7%) with higher levels of nutrient metabolizability, pancreatic digestive enzyme activities and low digesta viscosity. Notably, the group fed FBEs10% showed an increased villi height and a decreased crypt depth with a remarkable hyperactivity of duodenal glands. In addition, higher inclusion levels of FBEs boosted serum immune-related parameters and intestinal and breast muscle antioxidants status. Intestinal nutrient transporters encoding genes (GLUT-1, CAAT-1, LAT1 and PepT-1) and intestinal barriers encoding genes (MUC-2, JAM-2, occludin, claudins-1 and ß-defensin 1) were upregulated with higher dietary FBEs levels. In conclusion, feeding on FBEs10% positively enhanced broiler chickens' performance, feed efficiency and antioxidant status, and boosted intestinal barrier nutrient transporters encoding genes.

Prospects of new targeted nanotherapy combining liponiosomes with berberine to combat colorectal cancer development: An in vivo experimental model.

Colorectal cancer (CRC) is one of the most identified and deadly malignancies worldwide. It presents a serious challenge due to its quick growth, which finally culminates in severe malignancy. It is critical to improve the efficacy of berberine (BR) as an anticancer agent to overcome its limited bioavailability. Implementation of a novel, effective nanocarrier system of liponiosomes for BR (LipoNio.BR) can support mechanistic actions associated with its anti-CRC role. Following CRC induction in rats using 1,2 Dimethylhydrazine (40 mg DMH/kg/week), the potency and mechanistic actions of LipoNio.BR were assessed by evaluating the lesion severity and molecular mechanisms controlling oxidative stress, apoptosis, autophagy, and inflammatory responses, and conducting histopathological and immunohistochemistry examinations of colonic tissues. The results indicated that the severity of clinical signs comprising weight gain loss, increased diarrhea and rectal bleeding, and reduced survivability were greatly restored in the LipoNio.BR-treated group. LipoNio.BR remarkably reduced CRC development compared to FBR (free berberine), as it induced apoptosis via upregulating apoptotic genes (Bax and caspase3, increased up to 7.89 and 6.25-fold, respectively) and downregulating the anti-apoptotic gene Bcl-2 by 2.25-fold. LipoNio.BR mitigated the oxidative stress associated with CRC and maintained redox homeostasis. Notably, the excessive inflammatory response associated with CRC was prominently reduced following administration of LipoNio.BR [which decreased iterleukin (IL-B, IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), proliferating cell nuclear antigen (PCNA), follistatin, and activin BA (beta-A) expression]. LipoNio.BR modulated the expression of nuclear factor kappa B (NF-κB) and mammalian target of rapamycin (mTOR), which impacted tumor vascularity (decreased Vascular endothelial growth factor (VEGF) expression by 2.36-fold). The severity of the histopathological alterations in the colonic tissues, including the development of neoplastic epithelium and the invasion of some neoplastic masses, was greatly reduced in the LipoNio.BR group compared to the FBR-(free berberine) administrated group. Following CRC induction, immunohistochemical staining revealed that the overexpression of cyclin and COX-2 in colonic tissues were suppressed in the LipoNio.BR group. Taken together, these findings suggest that LipoNio.BR has a potential role in reducing CRC progression to a greater extent compared to free BR and could be considered a promising and potent therapy against CRC.

Stem cell therapies for autoimmune hepatitis.

Autoimmune hepatitis is a chronic inflammatory hepatic disorder which may cause liver fibrosis. Appropriate treatment of autoimmune hepatitis is therefore important. Adult stem cells have been investigated as therapies for a variety of disorders in latest years. Hematopoietic stem cells (HSCs) were the first known adult stem cells (ASCs) and can give rise to all of the cell types in the blood and immune system. Originally, HSC transplantation was served as a therapy for hematological malignancies, but more recently researchers have found the treatment to have positive effects in autoimmune diseases such as multiple sclerosis. Mesenchymal stem cells (MSCs) are ASCs which can be extracted from different tissues, such as bone marrow, adipose tissue, umbilical cord, and dental pulp. MSCs interact with several immune response pathways either by direct cell-to-cell interactions or by the secretion of soluble factors. These characteristics make MSCs potentially valuable as a therapy for autoimmune diseases. Both ASC and ASC-derived exosomes have been investigated as a therapy for autoimmune hepatitis. This review aims to summarize studies focused on the effects of ASCs and their products on autoimmune hepatitis.

Xeno-free trans-differentiation of adipose tissue-derived mesenchymal stem cells into glial and neuronal cells.

Mesenchymal stem cells (MSCs) are undifferentiated cells that have the ability of self-renewal and trans-differentiation into other cell types. They hold out hope for finding a cure for many diseases. Nevertheless, there are still some obstacles that limit their clinical transplantation. One of these obstacles are the xenogeneic substances added in either proliferation or differentiation media with subsequent immunogenic and infectious transmission problems. In this study, we aimed to replace fetal bovine serum (FBS), the main nutrient source for MSC proliferation with xeno-free blood derivatives. We tested the effect of human activated pure platelet-rich plasma (P-PRP) and advanced platelet-rich fibrin (A-PRF) on the proliferation of human adipose derived-MSCs (AD-MSCs) at different concentrations. For the induction of MSC neural differentiation, we used human cerebrospinal fluid (CSF) at different concentrations in combination with P-PRP to effect xeno-free/species-specific neuronal/glial differentiation and we found that media with 10% CSF and 10% PRP promoted glial differentiation, while media with only 10% PRP induced a neuron-like phenotype.