Curcumin alleviates spleen immunotoxicity induced by decabrominated diphenyl ethers (BDE-209) by improving immune function and inhibiting inflammation and apoptosis in broilers.

This study was conducted to assess the mitigating effects of curcumin (Cur) on immunotoxicity in the spleen of broilers induced by the polybrominated diphenyl ether BDE-209. Eighty one-day-old broilers were allocated to the following four groups: control group, BDE-209 (0.4 g/kg) group, BDE-209 (0.4 g/kg) + Cur (0.3 mg/kg) group, and Cur (0.3 mg/kg) group. Growth performance, immunological function, inflammation, and apoptosis were assessed after 42 days of treatment. The findings demonstrate that firstly, Cur restored spleen damage caused by BDE-209 by increasing body weight, decreasing feed-to-gain ratio, correcting the spleen index, and improving the histopathological structure of the spleen. Secondly, Cur relieved BDE-209-induced immunosuppression by increasing the levels of the immunoglobulins IgG, IgM, and IgA in the serum, as well as the levels of white blood cells and lymphocytes. The levels at which GATA binding protein 3, T-box expressed in T cells, interferon-γ, and interleukin (IL)- 4 are expressed were controlled. The ratio of T helper (Th) type 1 (Th1) to Th2 cells in the spleen of broilers was also controlled. Thirdly, Cur reduced the expression of Toll like receptor (TLR) 2, TLR4, nuclear factor (NF)-κB, IL-8, IL-6, and IL-1ß, which alleviated BDE-209-induced inflammation in broilers. Cur reduced BDE-209-induced apoptosis by increasing the expression of the bcl-2 protein, decreasing the expression of cleaved caspase-3 and bax proteins, decreasing the bax/bcl-2 protein ratio, and decreasing the mean optical density of TUNEL. These results suggest that Cur protects broiler spleens from BDE-209-induced immunotoxicity via modulating humoral immunity, the equilibrium between Th1 and Th2 cells, the TLRs/NF-κB inflammatory pathway, and the apoptotic pathway.

Amorphous solid dispersion preparation via coprecipitation improves the dissolution, oral bioavailability, and intestinal health enhancement properties of magnolol.

Magnolol (MAG) is a multifunctional plant polyphenol with anti-inflammatory, antibacterial, antioxidant and antitumor properties. In poultry, it has been shown to improve growth performance, antioxidant, immune functions and intestinal health. However, its applications are limited by poor solubility and low oral bioavailability. This study aimed at improving the water solubility of MAG through solid dispersion and investigating its effects in Arbor Acre (AA) broilers. Hydroxypropyl methylcellulose succinic acid (HPMCAS) was used as a carrier to prepare magnolol solid dispersions (MAG-HPMCAS SD) via antisolvent coprecipitation, which were characterized thereafter. Optimal formulation proportions for SD were screened by in vitro dissolution assays, while its effects on improving absorption were investigated via in vivo pharmacokinetic assays. In addition, we evaluated the effects of MAG-HPMCAS SD on growth performance, antioxidant status, and gut microbiota in AA broilers. The powder samples prepared via antisolvent coprecipitation did not exhibit a crystal diffraction peak of MAG in powder X-ray diffractions or melting point peak in differential scanning calorimetry, proving the successful preparation of an amorphous solid dispersion system. The in vitro dissolution assay showed that the cumulative dissolution rate of MAG-HPMCAS(LF) SD (2:8, w/w) was 100%. Pharmacokinetic analyses revealed that the peak concentration (Cmax) of MAG-HPMCAS SD was 5.07 ± 0.73 µg/mL, which was 1.76 times greater than that of MAG. In addition, AUC0-48 and t1/2 of MAG-HPMCAS SD were 40.49 ± 6.29 g·h/mL and 9.15 ± 3.23 h, respectively, which were 2.17 and 2.56 times higher than those of MAG. Supplementation of MAG-HPMCAS SD in AA broilers significantly increased ADG (7-14 d and 15-21 d) and reduced feed conversion ratio (15-21 d) (P < 0.05). Bacterial diversity in the MAG-HPMCAS SD-supplemented group was greater than in the Control and MAG-supplemented group. Supplementation of MAG-HPMCAS SD stimulated the proliferation of beneficial bacteria, such as Lactobacillaceae and Bifidobacteriaceae. In conclusion, the MAG-HPMCAS SD prepared by coprecipitation improved the dissolution rate, the bioavailability of MAG, growth promotion, antioxidant effects and gut health in broilers.

Dexmedetomidine attenuates hepatic ischemia-reperfusion injury-induced apoptosis via reducing oxidative stress and endoplasmic reticulum stress.

Dexmedetomidine (DEX) affords a hepatoprotective effect during ischemia-reperfusion (IR) injury (IRI); however, the underlying mechanism remains elusive. In this work, using a rat liver IR model and a BRL-3A cell hypoxia-reoxygenation (HR) model, we explored whether DEX protects the liver against IRI by decreasing oxidative stress (OS), endoplasmic reticulum stress (ERS), and apoptotic pathways. We found that DEX significantly increased SOD and GSH activity while decreasing ROS and MDA levels in BRL-3A cells, successfully preventing HR-induced OS damage. DEX administration reduced JNK, ERK, and P38 phosphorylation and blocked HR-induced MAPK signaling pathway activation. Additionally, DEX administration reduced the expression of GRP78, IRE1α, XBP1, TRAF2, and CHOP, which reduced HR-induced ERS. NAC prevented the MAPK pathway from being activated and inhibited the ERS pathway. Further research showed that DEX significantly reduced HR-induced apoptosis by suppressing the expression of Bax/Bcl-2 and cleaved caspase-3. Similarly, animal studies demonstrated DEX exerted a protective effect of the liver by alleviating histopathological injury and enhancing liver function, mechanically DEX reduced cell apoptosis in liver tissue by reducing oxidative stress and ERS. In conclusion, DEX mitigates OS and ERS during IR, thereby suppressing cell apoptosis, thus providing protection to the liver.

Effects of Lactiplantibacillus plantarum 19-2 on immunomodulatory function and gut microbiota in mice.

This study aims to evaluate the effects of Lactiplantibacillus plantarum 19-2 (L. plantarum 19-2) on mice treated with the alkylating agent cyclophosphamide (CTX). Our findings show that L. plantarum 19-2 restored the spleen and thymus index and the number of white blood cells and lymphocytes% in CTX treated mice. Serum immunoglobulin levels in CTX-treated mice were increased by L. plantarum 19-2. In addition, as compared to the model group, L. plantarum 19-2 upregulated the content of SIgA, while L. plantarum 19-2 regulates the mRNA and protein expression levels of GATA-3, T-bet, IFN-γ, and IL-4 in small intestinal tissues, which adjusted mucosal barriers, structural status, and the balance of Helper T-cell 1 and Helper T-cell 2. Lactiplantibacillus plantarum 19-2 regulated the distribution of intestinal flora in mice, promoting the growth of Bacteroides and Proteobacteria. In addition, L. plantarum 19-2 inhibited the growth of several harmful bacteria, including Actinobacteria and Firmicutes.

The game between host antiviral innate immunity and immune evasion strategies of senecavirus A - A cell biological perspective.

Innate immunity is the first line of the cellular host to defend against viral infection. Upon infection, viruses can be sensed by the cellular host's pattern recognition receptors (PRRs), leading to the activation of the signaling cascade and the robust production of interferons (IFNs) to restrict the infection and replication of the viruses. However, numerous cunning viruses have evolved strategies to evade host innate immunity. The senecavirus A (SVA) is a newly identified member of the Picornaviridae family, causing severe vesicular or ulcerative lesions on the oral mucosa, snout, coronary bands, and hooves of pigs of different ages. During SVA infection, the cellular host will launch the innate immune response and various physiological processes to restrict SVA. In contrast, SVA has evolved several strategies to evade the porcine innate immune responses. This review focus on the underlying mechanisms employed by SVA to evade pattern recognition receptor signaling pathways, type I interferon (IFN-α/ß) receptor (IFNAR) signaling pathway, interferon-stimulated genes (ISGs) and autophagy, and stress granules. Deciphering the antiviral immune evasion mechanisms by SVA will enhance our understanding of SVA's pathogenesis and provide insights into developing antiviral strategies and improving vaccines.

Laparoscopic colopexy in dogs.

Colopexy was accomplished in eight healthy mixed-breed dogs by use of a 3-portal laparoscopic technique without major intraoperative and postoperative complications. A permanent adhesion between the colon and the abdominal wall was observed. Concentrations of acute-phase C-reactive protein (CRP) were measured in serum as a marker of systemic inflammation postoperatively, and no relevant increase in CRP concentrations was found.

Laparoscopy for percutaneous tube cystostomy in dogs.

OBJECTIVE: To describe a laparoscopic technique for percutaneous tube cystostomy in dogs. DESIGN: Prospective cohort study. ANIMALS: 8 healthy mixed-breed dogs. PROCEDURES: A laparoscope portal and 2 instrumental portals were created in the abdomen of anesthetized dogs that were in dorsal recumbency. Intracorporeal suturing was performed to place 2 simple interrupted sutures between the ventral body wall and urinary bladder. A purse-string suture was placed in the urinary bladder wall approximately 1 cm cranial to the 2 simple interrupted sutures. A stab incision was made into the urinary bladder in the middle of the purse-string suture; an 8F Foley catheter was inserted through the stab incision and into the urinary bladder. Two other sutures were placed between the ventral body wall and bladder 1 cm cranial to the Foley catheter to create a cystopexy. The Foley catheter was secured to the skin with a finger-trap suture and was attached to a closed urine collection bag. All dogs underwent follow-up laparoscopy 1 month later. RESULTS: Median time for laparoscopic percutaneous tube cystostomy was 85 minutes (range, 72 to 103 minutes); there were no major intraoperative or postoperative complications. On follow-up laparoscopy, focal fibrous adhesions between the ventral body wall and bladder were observed in all dogs and omentum attached to the cystopexy site was observed in 2 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In this study, a laparoscopic percutaneous tube cystostomy was accomplished in healthy dogs by use of a 3-portal technique and appeared to be an effective and safe procedure.

[Effect of C21 steroidal glycoside from root of Cynanchum auriculatum on D-galactose induced aging model mice].

OBJECTIVE: To study the effect of C21 steroidal glycoside (CSG) from the root of Cynanchum auriculatum from Jiangsu on D-galactose (D-gal) induced aging model mice. METHOD: D-gal aging mouse model was established by cervicodorsal region subcutaneous injection with D-gal once a day for eight successive weeks. The mice in the normal control group (NCG, non-modeled) and the model control group (MCG, modeled but untreated) were treated with 1% CMC-Na. The model mice in the low, middle and high-dose CSG and Vitamin E treated groups were treated with a dose of (10, 20, 40, 100 mg x kg(-1) per day, respectively. The SOD activity, MDA content and telomerase activity in serum, heart, liver and brain tissues of mice were measured. RESULT: CSG could obviously increase the SOD activity and decrease the MDA level in serum, heart, liver and brain tissues in D-gal aging mice (P < 0.01). There was no significant difference between three CSG treated groups and Vitamin E treated groups. In comparison of telomerase activity between MCG and the treated groups, it was shown that there was a significant increase in serum in middle and high dose group, and in heart tissues in CSG and Vit E treated groups, but was not in liver and brain tissue. CONCLUSION: This study demonstrates that CSG can antagonize free radical injury, increase the SOD activity and decrease the MDA content of serum, heart, liver and brain in D-gal aging mice, and increase the telomerase activity in serum and heart tissues but not in liver and brain tissue.