Glycyrrhiza Extract and Curcumin Alleviates the Toxicity of Cadmium via Improving the Antioxidant and Immune Functions of Black Goats.

To investigate the mitigative effects of glycyrrhiza extract (GE) and curcumin (CUR) on the antioxidant and immune functions of the Guizhou black goat exposed to cadmium (Cd), 50 healthy Guizhou black goats (11.08 ± 0.22 kg, male, six months old) were used in a 60-day trial and were randomly assigned to five groups with 10 replicates per group, one goat per replicate. All goats were fed a basal diet, with drinking water and additives varying slightly between groups. Control group: tap water (0.56 µg·L-1 Cd); Cd group: drinking water containing Cd (20 mg Cd·kg-1·body weight, CdCl2·2.5H2O); GE group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 GE; CUR group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 CUR; combined group: drinking water containing Cd, at days 31 to 60, the basic diet had added 500 mg·kg-1 GE and CUR. Compared with the Cd group, GE and CUR significantly increased the levels of hemoglobin and red blood cell count in the blood, and the activities of serum antioxidant enzyme activity and immune function in the Guizhou black goat (p < 0.05). The treatment effect in the combined group was better than that in the GE and CUR groups. The results showed that GE and CUR improved the antioxidant and immune functions of the serum and livers of the Guizhou black goat and alleviated the toxicity damage of Cd contamination. This research has positive implications for both livestock management and human health.

Identification of exosome protein panels as predictive biomarkers for non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, primarily due to its propensity for metastasis. Patients diagnosed with localized primary cancer have higher survival rates than those with metastasis. Thus, it is imperative to discover biomarkers for the early detection of NSCLC and the timely prediction of tumor metastasis to improve patient outcomes. METHODS: Here, we utilized an integrated approach to isolate and characterize plasma exosomes from NSCLC patients as well as healthy individuals. We then conducted proteomics analysis and parallel reaction monitoring to identify and validate the top-ranked proteins of plasma exosomes. RESULTS: Our study revealed that the proteome in exosomes from NSCLC patients with metastasis was distinctly different from that from healthy individuals. The former had larger diameters and lower concentrations of exosomes than the latter. Furthermore, among the 1220 identified exosomal proteins, we identified two distinct panels of biomarkers. The first panel of biomarkers (FGB, FGG, and VWF) showed potential for early NSCLC diagnosis and demonstrated a direct correlation with the survival duration of NSCLC patients. The second panel of biomarkers (CFHR5, C9, and MBL2) emerged as potential biomarkers for assessing NSCLC metastasis, of which CFHR5 alone was significantly associated with the overall survival of NSCLC patients. CONCLUSIONS: These findings underscore the potential of plasma exosomal biomarkers for early NSCLC diagnosis and metastasis prediction. Notably, CFHR5 stands out as a promising prognostic indicator for NSCLC patients. The clinical utility of exosomal biomarkers offers the potential to enhance the management of NSCLC.

Characterization of Spray-Dried Microcapsules of Paprika Oleoresin Induced by Ultrasound and High-Pressure Homogenization: Physicochemical Properties and Storage Stability.

As an indispensable process in the microencapsulation of active substances, emulsion preparation has a significant impact on microencapsulated products. In this study, five primary emulsions of paprika oleoresin (PO, the natural colourant extracted from the fruit peel of Capsicum annuum L.) with different particle sizes (255-901.7 nm) were prepared using three industrialized pulverization-inducing techniques (stirring, ultrasound induction, and high-pressure homogenization). Subsequently, the PO emulsion was microencapsulated via spray drying. The effects of the different induction methods on the physicochemical properties, digestive behaviour, antioxidant activity, and storage stability of PO microencapsulated powder were investigated. The results showed that ultrasound and high-pressure homogenization induction could improve the encapsulation efficiency, solubility, and rehydration capacity of the microcapsules. In vitro digestion studies showed that ultrasound and high-pressure homogenization induction significantly increased the apparent solubility and dissolution of the microcapsules. High-pressure homogenization induction significantly improved the antioxidant capacity of the microcapsules, while high-intensity ultrasound (600 W) induction slowed down the degradation of the microcapsule fats and oils under short-term UV and long-term natural light exposure. Our study showed that ultrasound and high-pressure homogenization equipment could successfully be used to prepare emulsions containing nanoscale capsicum oil resin particles, improve their functional properties, and enhance the oral bioavailability of this bioactive product.

Cadmium Exposure Affects Serum Metabolites and Proteins in the Male Guizhou Black Goat.

Food safety and environmental pollution are the hotspots of general concern globally. Notably, long-term accumulation of trace toxic heavy metals, such as cadmium (Cd), in animals may endanger human health via the food chain. The mechanism of Cd toxicity in the goat, a popular farmed animal, has not been extensively investigated to date. Therefore, in this study, ten male goats (Nubian black goat × native black goat) were exposed to Cd via drinking water containing CdCl2 (20 mg Cd·kg-1·BW) for 30 days (five male goats per group). In this study, we used an integrated approach combining proteomics and metabolomics to profile proteins and metabolites in the serum of Cd-exposed goats. It was found that Cd exposure impacted the levels of 30 serum metabolites and 108 proteins. The combined proteomic and metabolomic analysis revealed that Cd exposure affected arginine and proline metabolism, beta-alanine metabolism, and glutathione metabolism. Further, antioxidant capacity in the serum of goats exposed to Cd was reduced. We identified CKM and spermidine as potential protein and metabolic markers, respectively, of early Cd toxicity in the goat. This study details approaches for the early diagnosis and prevention of Cd-poisoned goats.

Effects of Cadmium on Liver Function and Its Metabolomics Profile in the Guizhou Black Goat.

Cadmium (Cd) is a toxic heavy metal, which will lead to ecosystem contamination, threatening the life of grazing animals. Goats are an important grazing animal biomarker to evaluate Cd toxicity, but the effect of short-term and high-concentration Cd toxicity on goat liver function and its latent mechanism is still unclear. A total of ten male Guizhou black goats were randomly divided into two groups: CON group, sterilized tap water (no CdCl2), and Cd group (20 mg Cd·kg-1·BW, CdCl2⋅2.5H2O). The test lasted for 30 days. In this study, we found that Cd poisoning in drinking water affected significantly the distribution of Cd in the goat offal and tissues, and damaged the goat's immune function of the liver. With a metabolomics approach, 59 metabolites were identified. Metabolomics analysis suggested that Cd affected lipid and amino acid metabolism of the goat liver. Collectively, our results confirmed the effect of Cd on liver function and liver metabolism, and provided insights on the molecular basis for early warnings of Cd poisoning in goats.

Molybdenum fertilizer improved antioxidant capacity of Chinese Merino sheep under compound contamination.

To investigate the response of different levels of molybdenum (Mo) fertilizer to Chinese Merino sheep (Junken Type) grazing on natural heavy metal-contaminated meadows, this study was carried out in the Bayanbulak Grassland lying in the northwest of Xinjiang Uygur Autonomous Region, China. A total of 24-hm2 polluted meadows were fenced and were randomly divided into four groups (3 replication/group and 2 hm2/replication) applied 0-kg Mo, 1-kg Mo, 2-kg Mo, and 3-kg Mo (ammonium molybdate tetrahydrate) per hectare for the CON group, group I, group II, and group III, respectively. Seventy-two healthy 1-year-old Chinese Merino sheep (45.56 ± 2.35 kg) were randomly assigned to the tested pastures for 90 days. Compared with the CON group, the Mo content from fertilized groups and the Se content from group II and group III in serums and livers were significantly increased (P < 0.05), and the Cu content from fertilized groups in serums and livers was significantly decreased (P < 0.05). The levels of blood Hb and RBC, and the activities of serum SOD, CAT, GSH-Px, and Cp in group III, were significantly higher (P < 0.05) than those in the CON group, group I, and group II. Serum MDA content in group III was significantly lower (P < 0.05) than that in the other three groups. In summary, Mo fertilization improved the antioxidant capacity of grazing sheep and also reduced the toxic damage to Chinese Merino sheep grazing on natural grasslands contaminated by heavy metals, but Mo poisoning caused by excessive fertilization should be prevented.

The Invasive Potential of Hepatoma Cells Induced by Radiotherapy is Related to the Activation of Hepatic Stellate Cells and Could be Inhibited by EGCG Through the TLR4 Signaling Pathway.

Post-radiotherapy recurrence and metastasis of liver cancer were thought to arise from the invasion and metastasis of residual hepatocellular carcinoma cells, but it has now been shown to be closely related to the increased metastatic potential of residual liver cancer cells mediated by radiotherapy. The changes of liver microenvironment after radiotherapy also provide a favorable condition for promoting the metastatic potential of hepatocellular carcinoma. Studies have shown that radiation-induced activation of hepatic stellate cells (HSCs) is one of the main changes in the microenvironment of hepatocellular carcinoma. Therefore, we hypothesized that activated HSCs are involved in regulating the metastatic capacity of residual cancer cells after radiotherapy. The present study observed that 48 h co-culture of three human hepatoma cell lines (MHCC97-L, Hep-3B, LM3) with a irradiated human HSC line (LX-2) in a transwell chamber could significantly improve the invasion of the human hepatoma cells; and the culture supernatant of activated HSCs could also enhance the invasion of the hepatoma cells. In contrast, co-culture with irradiated hepatoma cells enhanced the invasion of LX-2 cells. In vitro, irradiation enhanced the activation phenotype and the toll like receptor 4 (TLR4) signaling pathway of LX-2 cells or primary mouse HSCs, which upregulated intercellular cell adhesion molecule-1 (ICAM1), laminin receptor (67 LR), Interleukin- 6 (IL-6), and CX3C chemokine ligand 1 (CX3CL1) and downregulated toll-interacting proteins. The compound (-)-epigallocatechin-3-gallate (EGCG) inhibited signal transduction of activated TLR4 and radiation-induced invasion of LX-2 cells by binding to 67 LR. These observations indicated that the enhancement of the metastatic potential of hepatoma cells after irradiation was relevant to the activation of HSCs, and the activation of TLR4 signaling pathway was involved in this process, which was inhibited by EGCG. Our results will help enhance the therapeutic efficacy of liver cancer stereotactic body radiation therapy to prevent and decrease the risks of post-radiotherapy recurrence and metastasis.

Nano-selenium and Macleaya cordata Extracts Improved Immune Function and Reduced Oxidative Damage of Sows and IUGR Piglets After Heat Stress of Sows in Late Gestation.

To investigate the effects of nano-selenium (nano-Se) and Macleaya cordata extracts (MCE) on immune function and oxidative damage of sows and intrauterine growth retardation (IUGR) piglets exposed to heat stress (HS) in large-scale farms, a 2 × 2 factorial design was adopted in this test, and the two factors were nano-Se (0, 0.50 mg/kg) and MCE (0, 500 mg/kg). A total of 80 sows ([Landrace × Yorkshire] × Duroc, parity 2) were used in a 25-day trial from day 90 of gestation to delivery with 20 replications per group and 1 sow per replication. The dietary treatments of sows were as follows: (1) CON group, basic diet (0.30 mg/kg added Se, sodium selenite); (2) Nano-Se group, basic diet (0.00 mg/kg added Se) + 0.50 mg/kg added nano-Se; (3) MCE group, basic diet (0.00 mg/kg added Se) + 500 mg/kg added MCE; and (4) Combined group, basic diet (0.00 mg/kg added Se) + 0.50 mg/kg added nano-Se and 500 mg/kg added MCE. The activities of serum SOD, CAT, and GSH-Px of sows and IUGR piglets were significantly increased in MCE group and combined group, and the MDA content was extremely decreased. There were extreme differences in serum IgG level of sows and IUGR piglets, colostrum, and serum IgM level of IUGR piglets in MCE group and combined group compared with CON group. Maternal combined diets increased greatly the levels of serum IL-10 and IFN-γ of sows and IUGR piglets, and decreased extremely the contents of serum IL-1ß and TNF-α. MCE alone or combination with nano-Se in sow diets decreased greatly mRNA level of Hsp70 and increased mRNA level of Hsp27 in sows and IUGR piglets. In conclusion, nano-Se and/or MCE can be added to sow diets for the amelioration of HS-induced oxidative damage through improving immune function.

Effect of Foliage Dressing in Nano-Potassium Molybdate on Daily Gain and Antioxidant Function in Grazing the Chinese Merino Sheep.

The study was implemented for exploring influences of nano-K2MoO4 on the daily gain and antioxidant function of Chinese merino sheep in the native pasture, Xinjiang Uygur Autonomous Region, Northwest of China. Eighty of the sheep, weight of (45.56 ± 2.35) kg, were randomly distributed to the tested areas for 90 days, 20 sheep/group. The findings showed that the contents of Mo and N in the forage of applying nano-K2MoO4 were extremely higher than those in the control pastures (P <0.01). The daily gain in the fertilized groups were remarkably lower than that in the control group (P <0.01). The harvest of forage in the fertilized pastures were significantly higher than those in control (P <0.01). The contents of Mo in blood and liver in grazing the Chinese merino sheep were extremely higher than those from the control group (P <0.01). The contents of Cu in blood and liver in grazing the Chinese merino sheep were extremely lower than those in the unfertilized pastures (P <0.01). The levels of hemoglobin (Hb), blood platelet (PLT), and erythrocyte count (RBC) in animals from the fertilized pastures were extremely lower than those in the control pastures (P < 0.01). The activities of SOD, GSH-Px, and CAT in serum were significantly lower than those in group C. The serum MDA levels were significantly higher than those in the control group (P < 0.01). In conclusion, the application of nano-K2MoO4 in pastures can greatly improve the yield of forage, but strikingly decreased the daily gain and antioxidant function in grazing the Chinese merino sheep.

Effects of Foliar Application of Nano-molybdenum Fertilizer on Copper Metabolism of Grazing Chinese Merino Sheep (Junken Type) on Natural Grasslands Under Copper and Cadmium Stress.

In recent decades, the groundwater contaminated by mineral development and metal smelting has seriously polluted natural grasslands, resulting in heavy metal residues in soils and forages exceeding the standard, especially copper (Cu) and cadmium (Cd). After animals intake contaminated forages, heavy metals may accumulate in animal tissues and threaten human health through the food chain. Previous studies found that molybdenum (Mo) fertilizer from ammonium molybdate or potassium molybdate could alleviate the decrease of antioxidant capacity caused by heavy metal poisoning, but the application of nano-Mo fertilizer in sheep is still lacking. To investigate the effects of nano-Mo fertilizer on Cu metabolism of grazing Chinese Merino sheep (Junken Type) on natural pastures under Cu and Cd stress, fertilizing experiment was carried out in the Bayanbulak Grassland in the northwest of Xinjiang Uygur Autonomous Region, China. A total of 24 hm2 fenced grassland contaminated by heavy metals was randomly divided into four groups (3 replications/group and 2 hm2/replication). The experimental groups were applied 0 g Mo, 100 g Mo, 200 g Mo, and 300 g Mo per hectare for the control group, group I, group II, and group III, respectively, through foliar spraying fertilization. A total of 72 Chinese Merino sheep (1 year old, 43.8 ± 2.3 kg) grazing on polluted natural grasslands, with 18 sheep per group, were randomly assigned to the experimental pastures for 30 days. The results showed that the Mo content in soil in group II and group III nwas higher than that in the control group (P < 0.05); the Cd content in soil in group II and group III was lower than that in the control group (P < 0.05), and the Cu content in soil in fertilized pastures was lower than that in the control group (P < 0.05). The Mo content in herbage in fertilized pastures was higher than that in the control group (P < 0.05), and the content of Cu in herbage in fertilized pastures was lower than that in the control group (P < 0.05). The contents of iron (Fe) and Mo in blood and liver of grazing animals from fertilized pastures were higher than that in the control group (P < 0.05). The Cd content in blood of grazing animals in group II and group III was lower than that in the control group (P < 0.05). The Cu content in blood and liver of grazing animals in fertilized pastures was lower than that in the control group (P < 0.05). The content of selenium (Se) in blood of grazing animals in group II and group III was higher than that in the control group (P < 0.05). The levels of blood including hemoglobin (Hb), erythrocyte count (RBC), and packed cell volume (PCV) in group II and group III were higher than that in the control group (P < 0.05). The white blood cell (RBC) count in group II and group III was lower than that in the control group (P < 0.05). The activities of serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and ceruloplasmin (Cp) in group II and group III were higher than that in the control group (P < 0.05). The content of malondialdehyde (MDA) in group II and group III was lower than that in the control group (P < 0.05). In conclusion, the application of nano-Mo fertilizer on Cu- and Cd-contaminated grasslands changed the contents of mineral elements in soil, forage, and blood of grazing sheep, improved the antioxidant capacity, affected the Cu metabolism of grazing Chinese Merino sheep caused by Cu and Cd pollutions, and alleviated the toxic damage of heavy metal pollutions.

Effects of Se-Enriched Malt on the Immune and Antioxidant Function in the Se-Deprived Reclamation Merino Sheep in Southern Xinjiang.

We have found that the Reclamation merino sheep in Southern Xinjiang, China, showed emaciation, stiff limbs, instability, and sudden death, which is related to the impairment of immune function and antioxidant capacity caused by selenium (Se) deficiency. The experiments were to study the effects of Se-enriched malt on the immune and antioxidant function in Se-deprived Reclamation merino sheep in Southern Xinjiang, China. The samples of soil and forage had been collected from tested pastures, and animal tissues were also collected in tested animals. The mineral content of soil, forage, and animal tissues was measured in the collected samples. Hematological indexes and biochemical values were also examined. The findings showed that the Se contents were extremely lower in affected soil and forage than those from healthy soil and forage (P < 0.01). The Se contents in affected blood and wool were also extremely lower than those from healthy blood and wool (P < 0.01). The values in glutathione peroxidase and total antioxidant capacity in affected serum samples were also extremely lower than those from healthy serum samples, and levels of malondialdehyde, total nitric oxide synthase, and lipid peroxide were extremely higher in affected serum samples than those from healthy serum samples (P < 0.01). Meanwhile, the values of hemoglobin, packed cell volume, and platelet count from affected blood were extremely lower than those from healthy blood (P < 0.01). The levels of interleukin (IL)-1ß, IL-2, tumor necrosis factor-alpha, immunoglobulin A, and immunoglobulin G in serum were extremely decreased in the affected Reclamation merino sheep (P < 0.01). The levels of IL-6 and immunoglobulin M in serum were extremely reduced in the affected Reclamation merino sheep compared to healthy animals (P < 0.01). The animals in affected pastures were orally treated with Se-enriched malt, and the Se contents in blood were extremely increased (P < 0.01). The immune function and antioxidant indicator returned to within the healthy range. Consequently, our findings were indicated that the disorder of the Reclamation merino sheep was mainly caused by the Se deficiency in soil and forage. The Se-enriched malt could not only markedly increase the Se content in blood but also much improve the immune function and the antioxidant capacity in the Se-deprived Reclamation merino sheep.

Effects of Se-Yeast on Immune and Antioxidant in the Se-Deprived Pishan Red Sheep.

The experiments were to study the effects of Se-yeast on immune and antioxidant in Selenium(Se)-deprived Pishan red sheep in Southern Xinjiang, China. The samples of soil, forage, and animal tissues were collected, and used for measuring mineral content, physiological parameter, and biochemical values. These findings showed that the Se contents in affected soil and forage were markedly lower than those from unaffected soil and forage (P < 0.01). Se in affected blood and wool were also extremely lower than those from healthy Pishan red sheep (P < 0.01). The hemoglobin, packed cell volume, platelet count, Glutathione peroxidase, and total antioxidant capacity in the affected Pishan red sheep were markedly lower than those from healthy ones too (P < 0.01). The levels of malondialdehyde, total nitric oxide synthase, and lipid peroxide in Pishan red sheep from affected pastures were extremely higher than those from healthy ones (P < 0.01). The levels of interleukin (IL)-1ß, Interleukin-2, tumor necrosis factor-α and interleukin-6 from serum were markedly decreased in affected Pishan red sheep(P < 0.01). The Pishan red sheep in Se-deprived pasture were treated by orally with Se-yeast, the amount of Se in the blood markedly increased in treated animals. Meanwhile, the immune and antioxidant indicator was returned to the healthy values. Consequently, our findings were indicated that Se-deprived forage caused oxidative damage, and a serious threat to the immune function in animals. The Se-yeast is more effective in the Se-deficient Pishan red sheep including blood Se content, immune function and the antioxidant capacity.

The combinations of sulfur and molybdenum fertilizations improved antioxidant capacity of grazing Guizhou semi-fine wool sheep under copper and cadmium stress.

Mineral development and metal smelting are the main sources of heavy metal pollution, and copper (Cu) and cadmium (Cd) are the most serious mineral elements in heavy metal pollution. Food chain is the main channel for Cu and Cd to enter human body. Excessive accumulation of Cu and Cd can lead to a variety of diseases and threaten human health. Therefore, it is urgent to repair Cu and Cd-contaminated soil. Previous several studies found that sulfur (S) and molybdenum (Mo) had the effect of alleviating the decrease of antioxidant capacity caused by heavy metal poisoning. To investigate the co-combinations of S and Mo fertilizations on antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-contaminated meadow, and explore the control methods of co-pollutions of Cu and Cd in natural pastures, fertilizing and grazing experiments were carried out in the Wumeng Prairie in the northwest of Guizhou Province, Southwest China. 24 hm2 Cu and Cd-polluted meadows were fenced, and were randomly divided into four groups with 3 replications per group and 2 hm2 per replication. The tested groups included the control group (no fertilizer) and the three treatment groups, applied 40 kg S + 1 kg Mo, 80 kg S + 2 kg Mo, and 120 kg S + 3 kg Mo per hectare for group I, group II, and group III, respectively. 72 healthy Guizhou semi-fine wool sheep (one year old, 33.9 ± 1.2 kg) were randomly assigned to the tested pastures with 18 sheep per group. The grazing experiment lasted for 60 days. The results showed that the contents of Mn, Zn, Mo, and S in herbage in fertilized pastures were higher than that in the control group (P < 0.05). The content of Cu in herbage in fertilized pastures was lower than that in the control group (P < 0.05). The contents of Mn, Zn, Mo, and S in serum of grazing Guizhou semi-fine wool sheep were higher than that in the control group (P < 0.05). The content of Cu in serum of grazing Guizhou semi-fine wool sheep was lower than that in the control group (P < 0.05). The levels of blood Hb, RBC, and PCV, and the activities of serum SOD, GSH-Px, T-AOC, CAT, and Cp in group Ⅲ were higher than that in the control group, group Ⅰ, and group Ⅱ (P < 0.05). The MDA content of sheep in group Ⅲ was lower than that in the other treatment sheep (P < 0.05). In summary, the combinations of S and Mo fertilizers influenced the mineral contents in herbage and serum of grazing Guizhou semi-fine wool sheep. The combinations of 120 kg S + 3 kg Mo fertilizer reduced the toxicity and improved antioxidant capacity of grazing Guizhou semi-fine wool sheep in Cu and Cd-polluted grasslands.

Aggravation of hepatic ischemia­reperfusion injury with increased inflammatory cell infiltration is associated with the TGF­ß/Smad3 signaling pathway.

Ischemia­reperfusion (IR) injury is a major challenge influencing the outcomes of hepatic transplantation. Transforming growth factor­ß (TGF­ß) and its downstream gene, SMAD family member 3 (Smad3), have been implicated in the pathogenesis of chronic hepatic injuries, such as hepatic fibrosis. Thus, the present study aimed to investigate the role of the TGF­ß/Smad3 signaling pathway on hepatic injury induced by IR in vivo. In total, 20 129S2/SvPasCrl wild­type (WT) mice were randomized into two groups; 10 mice underwent IR injury surgery and 10 mice were sham­operated. Histopathological changes in liver tissues and serum levels of alanine aminotransferase (ALT) were examined to confirm hepatic injury caused by IR surgery. The expression levels of TGF­ß1, Smad3 and phosphorylated­Smad3 (p­Smad3) were detected via western blotting. Furthermore, a total of five Smad3­/­ 129S2/SvPasCrl mice (Smad3­/­ mice) and 10 Smad3+/+ littermates received IR surgery, while another five Smad3­/­ mice and 10 Smad3+/+ littermates received the sham operation. Histopathological changes in liver tissues and serum levels of ALT were then compared between the groups. Furthermore, hepatic apoptosis and inflammatory cell infiltration after IR were evaluated in the liver tissues of Smad3­/­ mice and Smad3+/+ mice. The results demonstrated that the expression levels of TGF­ß1, Smad3 and p­Smad3 were elevated in hepatic tissue from WT mice after IR injury. Aggravated hepatic injury, increased apoptosis and enhanced inflammatory cell infiltration induced by hepatic IR injury were observed in the Smad3­/­ mice compared with in Smad3+/+ mice. Collectively, the current findings suggested that activation of the TGF­ß/Smad3 signaling pathway was present alongside the hepatic injury induced by IR. However, the TGF­ß/Smad3 signaling pathway may have an effect on protecting against liver tissue damage caused by IR injury in vivo.

Studies on Antioxidant Capacity in Selenium-Deprived the Choko Yak in the Shouqu Prairie.

The fencing device on pasture has seriously restricted the foraging range in grazing animals. As a result, the incidence of selenium (Se) deficiency is rising in grazing Choko yaks in the Shouqu prairie in Northwest China. To study the effect of Se deprivation on antioxidant capacity in the Choko yaks, the mineral contents in soil, forage, blood, and liver have been analyzed. The parameters of physiology and biochemistry in animal were also measured. The tested results showed that Se contents in soil and forage from tested pastures were very greatly lower than those in the control ranges (P < 0.01), and there were no extreme differences in other elements. Se contents in blood and the liver in tested animals were very extremely lower than those in the control yaks (P < 0.01). Levels of hemoglobin (Hb), erythrocyte (RBC), and hematocrit (HCT) were very extremely less than those in the control group (P < 0.01). Activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) in blood from the tested yaks were very much lower than those in the control animals (P < 0.01). Contents of malondialdehyde (MDA) in tested yaks were extremely higher than those in the control animals (P < 0.01). Therefore, it is suggested that Se-deficient forage in natural habitat not only influenced mineral contents in the blood and the liver but also causes serious harm to antioxidant function in the Choko yaks.

FSH receptor binding inhibitor depresses carcinogenesis of ovarian cancer via decreasing levels of K-Ras, c-Myc and FSHR.

The present study aimed to explore FSH receptor binding inhibitor (FRBI) effects on the levels of c-Myc, K-Ras and VEGF related to ovarian cancer, to evaluate the mRNA and protein levels of FSHR in the cumulus-oocyte complex (COCs). COCs were cultured for 24 h in the in vitro maturation (IVM) media replenished with 0, 10, 20, 30 and 40 µg/mL FRBI. Contents of c-Myc, K-Ras, VEGF, cAMP and IP3 in IVM media were detected with ELISA kits, respectively. The results indicated that the levels of FSHR protein and mRNA were determined with Western blotting. C-Myc contents of four FRBI + FSH-treated groups (COM groups) were reduced after IVM of COCs. C-Myc concentrations of COM-3 group was lower than the FSH group (p < .05). K-Ras and IP3 contents of COM-4 were decreased as compared to FSH group (p < .05). Expression levels of FSHR mRNAs and proteins in COM-4 group were smaller than that of FSH group. This study revealed that FRBI treatment could decrease c-Myc and K-Ras levels in the IVM medium fluids, and depress the FSHR levels of COCs. Expression levels of FSHR mRNAs and proteins of COM-4 group were significantly decreased. FRBI exerted its action via the signal pathway of IP3 and cAMP.

Effects of Nano-selenium Poisoning on Immune Function in the Wumeng Semi-fine Wool Sheep.

The Wumeng semi-fine wool sheep is vital to the production system in Southwest China. To study the effects of nano-selenium (Nano-Se) poisoning in the Wumeng semi-fine wool sheep, poisoning model was established. A total of 20 animals with an average initial body weight (BW) of 35.57 ± 3.31 kg were used in this study. After 1-week-long acclimatization period, all animals were randomly divided into two groups: (1) control, with no any treatment; (2) Nano-Se group, orally administered 5 mg Nano-Se (BW/kg/day). There were 10 replications/group and one sheep/replication. The experiment lasted for 30 days. Compared with the control, hemoglobin, erythrocyte count, and packed cell volume in Nano-Se group markedly decreased (P < 0.01), and the activities of serum lactate dehydrogenase, glutamic oxaloacetic transaminase, cereal third transaminase, and alkaline phosphatase in Nano-Se group significantly increased (P < 0.01). T3 and FT3 in serum in Nano-Se group were greatly lower than those in the control (P < 0.01). Contents of T4, FT4, and TSH in serum in Nano-Se group were extremely higher than those in the control (P < 0.01). Levels of IgG, IgM, IgA, interleukin 2 (IL-2), and tumor necrosis factor-alpha (TNF-α) in Nano-Se group were much lower than those of the control (P < 0.01), but levels of interleukin 6 (IL-6) and interleukin-1ß (IL-1ß) were greatly higher than those in the control (P < 0.01). Compared with the control, serum superoxide dismutase, glutathione peroxide, total antioxidant capacity, and catalase from Nano-Se group extremely decreased (P < 0.01), and content of serum malondialdehyde in Nano-Se group markedly increased (P < 0.01). The current results indicated that the blood parameters in the Wumeng semi-fine wool sheep were affected by Nano-Se poisoning, and the immune function and antioxidant capacity were greatly reduced too.

Identification and validation of critical alternative splicing events and splicing factors in gastric cancer progression.

Gene expression and alternative splicing (AS) interact in complex ways to regulate biological process which is associated with cancer development. Here, by integrated analysis of gene expression and AS events, we aimed to identify the hub AS events and splicing factors relevant in gastric cancer development (GC). RNA-seq data, clinical data and AS events of 348 GC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in 53 GCs. By bioinformatics methods, we found that gene AS event- and gene expression-mediated GC progression shared the same mechanisms, such as PI3K/AKT pathway, but the involved genes were different. Though expression of 17 hub AS events were confirmed in 53 GC tissues, only 10 AS events in seven genes were identified as critical candidates related to GC progression, notably the AS events (Exon Skip) in CLSTN1 and SEC16A. Expression of these AS events in GC correlated with activation of the PI3K/AKT pathway. Genes with AS events associated with clinical parameters and prognosis were different from the genes whose mRNA levels were related to clinical parameters and prognosis. Besides, we further revealed that QKI and NOVA1 were the crucial splicing factors regulating expression of AS events in GC, but not spliceosome genes. Our integrated analysis revealed hub AS events in GC development, which might be the potential therapeutic targets for GC.

Costunolide induces apoptosis and inhibits migration and invasion in H1299 lung cancer cells.

Costunolide being a sesquiterpene lactone, is known to have anticancer properties. The present study investigated the anticancer effects of costunolide against the H1299 human non­small­cell lung cancer (NSCLC) cell line. Inhibition of cell viability by costunolide was assessed via a MTT assay. Furthermore, the apoptotic rate was detected using Annexin V/propidium iodide labeling. A colony forming cell assay was performed to investigate the antiproliferative effects of costunolide. Wound healing and Transwell assays were performed to determine the inhibitory effects of costunolide on migration and invasion, respectively. Western blot analysis was undertaken to determine protein expression, and reverse transcription­quantitative PCR was performed to assess mRNA expression levels. The results demonstrated that costunolide inhibited the viability of H1299 cells, with a half maximal inhibitory concentration value of 23.93±1.67 µM and induced cellular apoptosis in a dose­dependent manner. Furthermore, the colony formation, migrative and invasive abilities of the H1299 cells were inhibited in a dose­ or time­dependent manner. The protein expression levels of E­cadherin increased and those of N­cadherin decreased following treatment with costunolide, which suggested that costunolide inhibited epithelial­to­mesenchymal transition. The mRNA levels of B­Raf, E­cadherin, N­cadherin, integrins α2 and ß1, as well as matrix metalloproteinases 2 were also found to be regulated costunolide. These findings indicate the potential of costunolide in the treatment of NSCLC.