Antioxidative, antidiabetic, and hypolipidemic properties of probiotic-enriched fermented camel milk (FCM) combined with Salvia officinalis L. leaves hydroalcoholic extract (SOHE) in streptozotocin-induced diabetes in rats were investigated. Phytochemicals analysis and antioxidant capacity indicated that S. officinalis contained high phenolics with super antioxidant activity. Subsequently, HPLC analysis demonstrated 13 phenolic acids and 14 flavonoids in considerable amounts with ferulic acid and resveratrol as predominant, respectively. The antidiabetic and hypolipidemic properties of FCM and SOHE were examined in a designed animal model consisting of seven treated groups for four weeks. There was a negative group (G1); the positive group (G2) received a single dose (50 mg kg⁻¹) of streptozotocin (STZ) by intraperitoneal injection (i.p.); in G3, diabetic rats (DRs) orally received 5 mL FCM kg⁻¹ daily; in G4, DRs orally received 50 mg GAE SOHE kg⁻¹ daily; in G5, DRs orally received 5 mL FCM contains 25 mg GAE SOHE kg⁻¹ daily; in G6, DRs orally received 5 mL FCM contains 50 mg GAE SOHE kg⁻¹ daily; in G7, DRs orally received 50 mg metformin kg⁻¹ daily. Combining FCM with SOHE at 25 or 50 mg kg⁻¹ exhibited a synergistic effect in significantly lowering random blood glucose (RBG), fasting blood glucose (FBG), and improved weight gain recovery %. The hypolipidemic effect of FCM + 50 mg GAE SOHE kg⁻¹ was significantly higher than using FCM or SOHE individually, and attenuation in triglycerides (TG), total cholesterol (CHO), and high- and low-density lipoproteins (HDL and LDL), and very-low-density lipoproteins (VLDL) was remarked. Combining FCM with SOHE at 25 or 50 mg kg⁻¹ ameliorated liver and kidney functions better than individual uses of FCM, SOHE, or metformin. Interestingly, FCM with 50 mg SOHE kg⁻¹ presented significant improvement in the activity of antioxidant enzymes, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and a substantial reduction in malonaldehyde (MDA) levels with 53.75%, 89.93%, 63.06%, and 58.69% when compared to the STZ group (G2), respectively. Histopathologically, administrating FCM + 25, 50 mg SOHE kg⁻¹ or 50 mg kg⁻¹ metformin showed a normal histological structure of both islets of Langerhans cells and acini. In conclusion, combining FCM with SOHE presented synergistic and therapeutical efficacy. It could be beneficial and profitable for controlling diabetes mellitus complications and protecting against oxidative stress.

Background and Aim: Rhazya stricta is a herbal plant widely used in traditional medicine due to its proficiency and naturalness with few side effects. In this study, we investigated the impact of using an R. stricta extract supplement on broiler chickens' performance, especially the immune system. Materials and Methods: In addition to the control group, one group received the methanol extract of R. stricta in drinking water for the first 2 weeks before being challenged with sheep erythrocytes (SRBCs), while the other group was challenged with SRBCs without receiving the R. stricta treatment. We evaluated cellular immunity by determining the phagocytic activity and lymphocyte (L) proliferation and assessed humoral immunity by quantification of the serum total IgM and IgG. We measured the serum levels of antioxidant enzymes and performed a histological examination of the spleen and the bursa of Fabricius (BF). Results: Our results indicate a significant enhancement in cellular immunity in the group supplemented with R. stricta as demonstrated by a significant increase in the phagocytic activity, L proliferation, and percentages of circulating L (p<0.05). The chickens treated with R. stricta exhibit an enhanced humoral response shown by a significant elevation in the serum levels of the total antibodies of the IgM and IgG isotypes, along with a notable increase in BF activity. Furthermore, R. stricta supplementation is associated with a significant increase in the serum levels of catalase and superoxide dismutase (p<0.05), along with a significant improvement in broilers' general performance, body weight, and feed efficiency. Conclusion: Our results suggest an immunomodulatory effect for the methanol extract of R. stricta and highlight the potential use of this plant in preventive and therapeutic medicine.

Background and Aim: Toxocara vitulorum is a bovine intestinal nematode. Immune pictures following infection are conflicting and stopping anthelmintic albendazole treatment recording reversed liver abnormalities. The purpose of this work was to evaluate the therapeutic potential of bone marrow mesenchymal stem cells (BMMSCs) therapy, subsequent to albendazole administration in rats infected with T. vitulorum. Materials and Methods: The ultrasonographic and histopathological examinations as well as serum liver enzymes activity and the kinetics of recovery were investigated. The correlation of cell-mediated and humoral immune pictures was assessed by assaying immunoglobulins, splenocytes viability, phagocytic index, and Th1/Th2 cytokines. Results: The cultured BMMSCs counting were 4.21×104 cells/cm2 with 96.03% viability. Flow-cytometric analysis indicated positive CD90 (82%), CD105 (79%) and negative CD34 (0.37%), CD45 (0.42%), attesting to the suitability of the isolated BMMSCs for use in therapy. Transplantation of BMMSCs after albendazole administration significantly reduced the release of liver enzymes (p<0.05) indicating liver cellularity improvement. The ultrasonographic, macroscopic, and histopathological findings confirmed the biochemical results. Significant elevation in the levels of tumor necrosis factor (TNF)-α and interferon (INF)-γ with a decline in interleukin (IL)-4 was observed in the untreated model (p<0.05). However, albendazole treatment followed by BMMSCs therapy significantly lowered the release of TNF-α and INF-γ, associated with significant production of IL-4 and IL-10 (p<0.05). Conclusion: The final results indicated that the liver functions, histopathological findings, and immune parameters were aggravated after experimental T. vitulorum infection. Albendazole treatment followed by BMMSCs therapy was found to assist in regeneration of injured hepatic tissue. Besides, it appeared to modulate host defensive immune responses against T. vitulorum antigens. This work could define more clearly the events that manipulate the host immune, histopathological, and biochemical responses to minimize obstacles in using stem cell therapy in animal toxocariosis.

| The effects of Lycium shawii and Rhanterium epapposum supplementation on humoral and cellular immune responses of chickens have not been investigated. Chickens supplemented with either R. epapposum or Lycium shawii extracts and challenged with sheep erythrocytes (SRBC) exhibited a significant increase in body weight gain as compared to the control group (P<0.05). The data showed a significant increase in the serum activities of catalase (CAT) and superoxide dismutase (SOD) in the chickens pretreated with the R. epapposum extract (P<0.05). In contrast, only the activities of the SOD and TAC enzymes were significantly elevated in the Lycium shawii recipient group (P<0.05). Significant increases (P<0.05) in the in-vitro phagocytic index of chickens supplemented with either extract was noted, with the phagocytic index remaining significantly elevated (P< 0.01) throughout the experiment only in the R. epapposum group. In response to mitogenic stimulation, lymphocytes obtained from the R. epapposum and Lycium shawii groups consumed significantly higher amounts of glucose relative to the control group (P< 0.01 and P< 0.05, respectively). Chickens pretreated with Lycium shawii had significantly higher levels of serum IgM (P<0.05), with the IgG levels being significantly higher in the chickens pretreated with either extract, as well as in the SRBC group (P<0.01). The IgG levels remained significantly elevated (P<0.01) in the Lycium shawii recipient chickens until the experiment’s termination. It can be concluded that the plant extracts used in the present study had stimulatory effects on the chicken’s immune systems and broilers’ performance in general.

Background and Aim: A delivery system consisting of bone marrow mesenchymal stem cells (MSCs) loaded with polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles (SPIONs) was constructed to treat a rat model of cisplatin (Cis)-induced nephrotoxicity with 1/10 of the common dose of anti-tumor necrosis factor-alpha (TNF-α) antibodies (infliximab). Materials and Methods: Morphology, size, crystallinity, molecular structure, and magnetic properties of uncoated and PEG-coated SPIONs were analyzed. A delivery system consisting of MSCs containing infliximab-labeled PEG-coated SPIONs (Infliximab-PEG-SPIONs-MSCs) was generated and optimized before treatment. Fifty female Wistar rats were divided into five equal groups: Group 1: Untreated control; Group 2 (Cis): Rats were administered Cis through intraperitoneal (i.p.) injection (8 mg/kg) once a week for 4 weeks; Group 3 (Infliximab): Rats were injected once with infliximab (5 mg/kg), i.p. 3 days before Cis administration; Group 4 (Cis + MSCs): Rats were injected with Cis followed by an injection of 2 × 106 MSCs into the tail vein twice at a 1-week interval; and Group 5 (Cis + Infliximab (500 μg/kg)-PEG-SPIONs-MSCs): Rats were injected with the delivery system into the tail vein twice at a 1-week interval. Besides histological examination of the kidney, the Doppler ultrasound scanner was used to scan the kidney with the Gray-color-spectral mode. Results: In vivo, intra-renal iron uptake indicates the traffic of the delivery system from venous blood to renal tissues. Cis-induced nephrotoxicity resulted in a significant increase in TNF-α and malondialdehyde (MDA) (p < 0.05), bilirubin, creatinine, and uric acid (p < 0.01) levels compared with the untreated control group. The different treatments used in this study resulted in the amelioration of some renal parameters. However, TNF-α levels significantly decreased in Cis + Infliximab and Cis + MSCs (p < 0.05) groups. The serum levels of MDA significantly decreased in Cis + Infliximab (p < 0.05), Cis + MSCs (p < 0.05), and Cis + Infliximab-PEG-SPIONs-MSCs (p < 0.01). Furthermore, the serum activities of antioxidant enzymes were significantly elevated in the Cis + MSCs and Cis + Infliximab-PEG-SPIONs-MSCs groups (p < 0.05) compared to the Cis-induced nephrotoxicity rat model. Conclusion: With the support of the constructed MSCs-SPIONs infliximab delivery system, it will be possible to track and monitor cell homing after therapeutic application. This infliximab-loading system may help overcome some challenges regarding drug delivery to the target organ, optimize therapeutics' efficacy, and reduce the dose. The outcomes of the current study provide a better understanding of the potential of combining MSCs and antibodies-linked nanoparticles for the treatment of nephrotoxicity. However, further investigation is recommended using different types of other drugs. For new approaches development, we should evaluate whether existing toxicity analysis and risk evaluation strategies are reliable and enough for the variety and complexity of nanoparticles.

This study assessed the efficacy of a bivalent IBV vaccination (H120/D274) against GI-23 (variant II) and the antiviral and immunostimulatory properties of dietary Nigella sativa plus β-glucan (NSG). A total of 186 one-day-old broiler chicks were used as follows: 1st group (n=42) received IBV vaccine (prime: 7- and post: 14- day of age) (VAX), 2nd group (n=42) received the additive without vaccination (NSG), 3rd group (n=42) received both the vaccine and additive (VAX-NSG), and 4th group (n=60) received neither vaccine nor additive (CTRL). The 4th group was subdivided on the challenging day to negative (CTRL-N) and positive (CTRL-P) control subgroups. All groups except CTRL-N were challenged via naso/ocular route with IBV Variant II at 14 days post 2nd vaccination (PV). Clinical protection, antibody titers, cytokine expression, immune organ indices, viral shedding, and renal and tracheal histopathological lesions were evaluated. Body weight loss% at 1-week post-challenge (pc) in VAX, NSG, and VAX-NSG was 28.47%, 31.28%, and 23.54%, respectively, compared to CTRL-P (43.72 %) (P<0.05). Remarkably, NSG group showed milder tracheal and renal histopathological lesions than VAX group at 3 and 7 dpc, while VAX-NSG group displayed normal histology. Oropharyngeal IBV shedding was successfully reduced by the vaccination regimen; the VAX-NSG group showed the lowest level (P<0.05). Splenic IL-6 and TNF-α mRNA expression was upregulated at 3- and 7-dpc in CTRL-P birds (P<0.05). They were significantly downregulated in VAX-NSG, VAX, and NSG groups (P<0.05). At 7 dpc, IBV reduced the CTRL-P group's bursa, thymus, and spleen indices (P<0.05) that were significantly reversed in other challenged groups. VAX, NSG, and VAX-NSG groups induced higher lacrimal IgA titers than the control (P<0.05) at weekly intervals PV; while pc, they were lower than CTRL-P (P<0.05). However, serum IgG titers were higher in the VAX group than VAX-NSG group PV, and the opposite was observed at 7 and 10 dpc (P<0.05). Conclusion, the combination of dietary NSG with the heterologous IBV vaccine (H120/D274) showed synergistic effects to stop variant II viral shedding by the 10th dpc, increase anti-inflammatory effects, prevent renal and tracheal histopathological lesions, and significantly reduce body weight loss post challenge.