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In the context of the potential immunomodulatory properties of curcumin in counteracting the detrimental effects of concurrent exposure to Deoxynivalenol (DON) and Aflatoxin B1 (AFB1), a comprehensive 28-days trial was conducted utilizing 60 randomly allocated mice divided into four groups. Administration of curcumin at a dosage of 5 mg/kg body weight in conjunction with DON at 0.1 mg/kg and AFB1 at 0.01 mg/kg body weight was undertaken to assess its efficacy. Results indicated that curcumin intervention demonstrated mitigation of splenic structural damage, augmentation of serum immunoglobulin A (IgA) and immunoglobulin G (IgG) levels, elevation in T lymphocyte subset levels, and enhancement in the mRNA expression levels of pro-inflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-6. Furthermore, curcumin exhibited a suppressive effect on apoptosis in mice, as evidenced by decreased activity of caspase-3 and caspase-9, reduced expression levels of pro-apoptotic markers Bax and Cytochrome-c (Cyt-c) at both the protein and mRNA levels, and the maintenance of a balanced expression ratio of mitochondrial apoptotic regulators Bax and Bcl-2. Collectively, these findings offer novel insights into the therapeutic promise of curcumin in mitigating immunosuppression and apoptotic events triggered by mycotoxin co-exposure. [ABSTRACT FROM AUTHOR]

Human sulfotransferases 1A3 (SULT1A3) has received particular interest, due to their functions of catalyzing the sulfonation of numerous phenolic substrates, including bioactive endogenous molecules and therapeutic agents. However, the regulation of SULT1A3 expression and the underlying mechanism remain unclear. Here, we aimed to investigate the regulation effects of bile acid‐activated farnesoid X receptor (FXR) on SULT1A3 expression, and to shed light on the mechanism thereof. Our results demonstrated that FXR agonists (CDCA and GW4064) significantly inhibit the expression of SULT1A3 at mRNA and protein levels. In addition, overexpression of FXR led to decrease in SULT1A3 expression and knockdown of FXR significantly induced the expression of SULT1A3 in protein and mRNA levels, confirming that FXR expression manifestly showed negative regulatory effect on basal SULT1A3 expression. Furthermore, a combination of luciferase reporter gene and CHIP assays showed that FXR repressed SULT1A3 transcription through direct binding to the region at base pair positions −664 to −654. In conclusion, this study for the first time confirmed FXR was a negative transcriptional regulator of human SULT1A3 enzyme. [ABSTRACT FROM AUTHOR]

Chronic tubulointerstitial nephropathy (CTIN) is one of the most common kidney diseases. However, treatment for CTIN has multiple limits. Adjuvant therapy through nutritional regulation has become a hot research topic at present. Icariin (ICA), an extraction of Chinese herbal medicine epimedium, has many pharmacological functions including anti-inflammation and tonifying kidney. Selenomethionine (SeMet) possesses the effects of antioxidant and lightening nephrotoxicity. However, little is known about the combined nephroprotection of them. This study was investigated to evaluate the joint effects of ICA and SeMet on CTIN and explore the mechanism. Based on a novel CTIN model developed in our previous study, mice were randomly divided into five groups (a: control; b: model; c: model + ICA; d: model + SeMet; e: model + ICA + SeMet). Renal tubule epithelial cells were treated with cyclosporine A and ochratoxin A without/with ICA or/and SeMet. The results showed that ICA or/and SeMet ameliorated CTIN by inhibiting the uptrends of blood urine nitrogen, serum creatinine, urine protein, urine gravity, histopathological damage degree and collagen I deposition. ICA or/and SeMet also increased cell proliferation and decreased apoptosis and the expression of transforming growth factor-beta 1 and α-smooth muscle actin. Emphatically, ICA and SeMet joint had better nephroprotection than alone in most indexes including fibrosis. Furthermore, ICA and SeMet joint decreased the activation of toll-like receptor 4 (TLR4)/NFκB pathway induced by CTIN. TLR4 overexpression counteracted the joint protection of ICA and SeMet. Therefore, ICA and SeMet in combination could protect against CTIN through blocking TLR4/NFκB pathway. The study will provide novel insights to explore an adjuvant therapeutic orientation. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA), frequently existing in the food and feeds, could induce immunotoxicity. Porcine circovirus type 2 (PCV2), as a primary causative agent of porcine circovirus–associated disease, also could induce immunosuppression. However, it is still unknown whether PCV2 infection impacts OTA-induced immunotoxicity. The pigs and porcine alveolar macrophages (PAMs) were used as the model in the present experiment. The results in vivo indicated that PCV2 infection exacerbated OTA-induced immunotoxicity, NF-κB p65 phosphorylation, and TLR4 and MyD88 mRNA and protein expression in spleen. The results in vitro showed that OTA at 7.0 and 9.0 μM decreased cell viability and increased LDH release of PAMs without PCV2 infection. However, with PCV2 infection, OTA at 5.0, 7.0 and 9.0 μM significantly decreased cell viability and increased LDH release compared with absence of PCV2 infection. In addition, OTA at 5.0 and 7.0 μM significantly increased Annexin V/PI-positive rate, apoptosis of nuclear, γ-H2AX foci, IL-1α and TNF-α expression in PAMs with PCV2 infection compared with absence of PCV2 infection. In addition, PCV2 infection enhanced OTA-induced TLR4 and MyD88 mRNA and protein expression and NF-κB p65 phosphorylation. Knockdown of TLR4 alleviated the exacerbating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage in PAMs. These results indicated that PCV2 infection aggravated OTA-induced immunotoxicity and reduced the dose of OTA-induced immunotoxicity via TLR4/NF-κB p65 signaling pathway, which could provide basis for establishing limits for OTA. [Display omitted] • PCV2 infection aggravated OTA-induced immunotoxicity in pigs and PAMs. • PCV2 infection aggravated OTA-induced TLR4/ NF-κB p65 signaling pathway in pigs and PAMs. • TLR4-siRNA eliminated the aggravating effects of PCV2 infection on OTA-induced cytotoxicity, apoptosis and DNA damage. • PCV2 infection aggravated OTA-induced immunotoxicity by promoting TLR/NF-κB p65 signaling pathway. [ABSTRACT FROM AUTHOR]

Purpose: Acute lung injury (ALI) is characterized by impairment in gas exchange and/or lung mechanics that leads to hypoxemia with the presence of diffuse pulmonary infiltrate. Assessments of lung injury play important roles in the development of rational medical countermeasures. The purpose of this study is to investigate the molecular mechanisms of phosgene-induced lung injury. Methods: We downloaded the gene expression profile of lung tissue from mice exposed to air or phosgene from gene expression omnibus database and identified differentially expressed genes (DEGs) in ALI. Furthermore, we constructed a protein-protein interaction (PPI) network and identified network clusters. Results: In total, 582 DEGs were found and 4 network clusters were identified in the constructed PPI network. Gene set enrichment analysis found that DEGs were mainly involved in mitochondrion organization and biogenesis, mRNA metabolic process, negative regulation of transferase activity or catalytic activity, and coenzyme metabolic process. Pathways of spliceosome, glutathione metabolism, and cell cycle were dysregulated in phosgene-induced ALI. Besides, we identified four genes, including F3, Meis1, Pvf, and Cdc6 in network clusters, which may be used as biomarkers of phosgene-induced ALI. Conclusions: Our results revealed biological processes and pathways involved in phosgene-induced ALI and may expand understandings of phosgene-induced ALI. However, further experiments are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

• RNA-seq was analyzed in Streptococcus mutans with disruption of LuxS/AI-2 quorum sensing and recovery of methyl cycle. • 84 genes were detected, which only affected by the LuxS/AI-2 QS system other than methyl cycle. • The LuxS/AI-2 QS system mainly affects ABC transporters and carbohydrate transport, transformation and metabolism. The LuxS/AI-2 quorum sensing (QS) system has critical roles in Streptococcus mutans cariogenicity. Whereas the molecular and cellular mechanisms of the LuxS/AI-2 QS system are not thoroughly understood. Given that LuxS has roles in QS and methyl cycle, its mutation can cause QS deficiency and methyl cycle disruption. The aim of this study was to investigate effects of the LuxS/AI-2 QS system on gene expression in Streptococcus mutans when methyl cycle was recovered with exogenous sahH gene. Our previous study introduced the exogenous sahH gene from Pseudomonas aeruginosa into an S. mutans luxS-null strain to restore the disrupted methyl cycle, and this produced the solely the LuxS/AI-2 QS system deficient strain. Here, we analyzed the transcriptomics of this strain to get insights into the molecular mechanisms of the LuxS/AI-2 QS system applying RNA-seq. With recovery of methyl cycle, 84 genes didn't change in expression trends in S. mutans luxS-null strain. These genes mainly encode the ABC transporters, sugar transporter EII and enzymes of carbohydrate metabolism, and are rich in the Phosphotransferase system, Fructose and mannose metabolism, Amino sugar and nucleotide sugar metabolism, Galactose metabolism, Glycolysis/Gluconeogenesis, RNA degradation, Lysine biosynthesis, and Glycine, serine and threonine metabolism. The LuxS/AI-2 QS system may mainly affect ABC transporters and carbohydrate transport, transformation and metabolism via EII subunits and enzymes to influence virulence-associated traits without effects of methyl cycle in Streptococcus mutans. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the effects of zinc-enriched probiotics (ZnP) on growth performance, antioxidant status, immune function, related gene expression, and morphological characteristics of Wistar rats raised under high heat stress condition during summer. 36, 6-week-old male Wistar rats were randomly divided into three groups; fed with basal diet (control), basal diet with probiotics (P), and basal diet with zinc-enriched probiotics supplementation (ZnP, 100 mg/L), for 40 consecutive days. Blood samples were collected through intracardiac method on the last day of experiment and tissues were collected from liver, heart, and kidneys. The results revealed that both P and ZnP significantly (P < 0.05) enhanced growth performance. However, ZnP remarkably increased glutathione content, glutathione peroxidase, and superoxide dismutase activities but reduced malondialdehyde level in serum of the Wistar rats. The concentration of IL-2, IL-6, and IFN-γ was significantly (P < 0.05) increased with treatments of P and ZnP compared to control group while IL-10 was significantly (P < 0.05) decreased. Additionally, the expression of SOD1, SOD2, MT1, and MT2 genes was significantly (P < 0.05) up-regulated with the treatment of ZnP, but Hsp90 and Hsp70 heat shock genes were significantly (P < 0.05) down-regulated with the treatment of P and ZnP, respectively. Hematoxylin and Eosin staining showed that both P and ZnP supplementation treatments induced changes in villus height and intestinal wall thickness. In conclusion, zinc-enriched probiotics supplementation can improve the growth performance of Wistar rats under high ambient temperature through enhancing antioxidant status, immune function, related genes expression, and intestinal morphological characteristics. This product may serves as a potential nutritive supplement for Wistar rats under high heat stress conditions. [ABSTRACT FROM AUTHOR]