Folic Acid and Taurine Alleviate the Impairment of Redox Status, Immunity, Rumen Microbial Composition and Fermentation of Lambs under Heat Stress.

The aim of this study was to investigate if the supplementation of folic acid and taurine can relieve the adverse effects of different levels of heat stress (HS) on growth performance, physiological indices, antioxidative capacity, immunity, rumen fermentation and microbiota. A total of 24 Dorper × Hu crossbred lambs (27.51 ± 0.96 kg) were divided into four groups: control group (C, 25 °C), moderate HS group (MHS, 35 °C), severe HS group (SHS, 40 °C), and the treatment group, under severe HS (RHS, 40 °C, 4 and 40 mg/kg BW/d coated folic acid and taurine, respectively). Results showed that, compared with Group C, HS significantly decreased the ADG of lambs (p < 0.05), and the ADG in the RHS group was markedly higher than in the MHS and SHS group (p < 0.05). HS had significant detrimental effects on physiological indices, antioxidative indices and immune status on the 4th day (p < 0.05). The physiological indices, such as RR and ST, increased significantly (p < 0.05) with the HS level and were significantly decreased in the RHS group, compared to the SHS group (p < 0.05). HS induced the significant increase of MDA, TNF-α, and IL-ß, and the decrease of T-AOC, SOD, GPx, IL-10, IL-13, IgA, IgG, and IgM (p < 0.05). However, there was a significant improvement in these indices after the supplementation of folic acid and taurine under HS. Moreover, there were a significant increase in Quinella and Succinivibrio, and an evident decrease of the genera Rikenellaceae_RC9_gut_group and Asteroleplasma under HS (p < 0.05). The LEfSe analysis showed that the genera Butyrivibrio, Eubacterium_ventriosum_group, and f_Bifidobacteriaceae were enriched in the MHS, SHS and RHS groups, respectively. Correlated analysis indicated that the genus Rikenellaceae_RC9_gut_group was positively associated with MDA, while it was negatively involved in IL-10, IgA, IgM, and SOD (p < 0.05); The genus Anaeroplasma was positively associated with the propionate and valerate, while the genus Succinivibrio was negatively involved in TNF-α (p < 0.05). In conclusion, folic acid and taurine may alleviate the adverse effects of HS on antioxidant capacity, immunomodulation, and rumen fermentation of lambs by inducing changes in the microbiome that improve animal growth performance.

Nano-modulators with the function of disrupting mitochondrial Ca2+ homeostasis and photothermal conversion for synergistic breast cancer therapy.

Breast cancer treatment has been a global puzzle, and apoptosis strategies based on mitochondrial Ca2+ overload have attracted extensive attention. However, various limitations of current Ca2+ nanogenerators make it difficult to maintain effective Ca2+ overload concentrations. Here, we constructed a multimodal Ca2+ nano-modulator that, for the first time, combined photothermal therapy (PTT) and mitochondrial Ca2+ overload strategies to inhibit tumor development. By crosslinking sodium alginate (SA) on the surface of calcium carbonate (CaCO3) nanoparticles encapsulating with Cur and ICG, we prepared a synergistic Ca2+ nano-regulator SA/Cur@CaCO3-ICG (SCCI). In vitro studies have shown that SCCI further enhanced photostability while preserving the optical properties of ICG. After uptake by tumor cells, SCCI can reduce mitochondrial membrane potential and down-regulate ATP production by producing large amounts of Ca2+ at low pH. Near-infrared light radiation (NIR) laser irradiation made the tumor cells heat up sharply, which not only accelerated the decomposition of CaCO3, but also produced large amounts of reactive oxygen species (ROS) followed by cell apoptosis. In vivo studies have revealed that the Ca2+ nano-regulators had excellent targeting, biocompatibility, and anti-tumor effects, which can significantly inhibit the proliferation of tumor cells and play a direct killing effect. These findings indicated that therapeutic strategies based on ionic interference and PTT had great therapeutic potential, providing new insights into antitumor therapy.

Understanding sorafenib-induced ferroptosis and resistance mechanisms: Implications for cancer therapy.

Sorafenib is an important first-line treatment option for liver cancer due to its well-characterized safety profile. While novel first-line drugs may have better efficacy than Sorafenib, they also have limitations such as worse safety and cost-effectiveness. In addition to inducing apoptosis, Sorafenib can also trigger ferroptosis, which has recently been recognized as an immunogenic cell death, unleashing new possibilities for cancer treatment. However, resistance to Sorafenib-induced ferroptosis remains a major challenge. To overcome this resistance and augment the efficacy of Sorafenib, a wide range of nanomedicines has been developed to amplify its pro-ferroptotic effects. This review highlights the mechanisms underlying Sorafenib-triggered ferroptosis and its resistance, and outlines innovative strategies, particularly nanomedicines, to overcome ferroptosis resistance. Moreover, we summarize molecular biomarkers that signify resistance to Sorafenib-mediated ferroptosis, which can assist in predicting therapeutic outcomes.

The Application of Ethnomedicine in Modulating Megakaryocyte Differentiation and Platelet Counts.

Megakaryocytes (MKs), a kind of functional hematopoietic stem cell, form platelets to maintain platelet balance through cell differentiation and maturation. In recent years, the incidence of blood diseases such as thrombocytopenia has increased, but these diseases cannot be fundamentally solved. The platelets produced by MKs can treat thrombocytopenia-associated diseases in the body, and myeloid differentiation induced by MKs has the potential to improve myelosuppression and erythroleukemia. Currently, ethnomedicine is extensively used in the clinical treatment of blood diseases, and the recent literature has reported that many phytomedicines can improve the disease status through MK differentiation. This paper reviewed the effects of botanical drugs on megakaryocytic differentiation covering the period 1994-2022, and information was obtained from PubMed, Web of Science and Google Scholar. In conclusions, we summarized the role and molecular mechanism of many typical botanical drugs in promoting megakaryocyte differentiation in vivo, providing evidence as much as possible for botanical drugs treating thrombocytopenia and other related diseases in the future.

Novel chemical-structure TPOR agonist, TMEA, promotes megakaryocytes differentiation and thrombopoiesis via mTOR and ERK signalings.

BACKGROUND: Non-peptide thrombopoietin receptor (TPOR) agonists are promising therapies for the mitigation and treatment of thrombocytopenia. However, only few agents are available as safe and effective for stimulating platelet production for thrombocytopenic patients in the clinic. PURPOSE: This study aimed to develop a novel small molecule TPOR agonist and investigate its underlying regulation of function in megakaryocytes (MKs) differentiation and thrombopoiesis. METHODS: A potential active compound that promotes MKs differentiation and thrombopoiesis was obtained by machine learning (ML). Meanwhile, the effect was verified in zebrafish model, HEL and Meg-01 cells. Next, the key regulatory target was identified by Drug Affinity Responsive Target Stabilization Assay (DARTS), Cellular Thermal Shift Assay (CETSA), and molecular simulation experiments. After that, RNA-sequencing (RNA-seq) was used to further confirm the associated pathways and evaluate the gene expression induced during MK differentiation. In vivo, irradiation (IR) mice, C57BL/6N-TPORem1cyagen (Tpor-/-) mice were constructed by CRISPR/Cas9 technology to examine the therapeutic effect of TMEA on thrombocytopenia. RESULTS: A natural chemical-structure small molecule TMEA was predicted to be a potential active compound based on ML. Obvious phenotypes of MKs differentiation were observed by TMEA induction in zebrafish model and TMEA could increase co-expression of CD41/CD42b, DNA content, and promote polyploidization and maturation of MKs in HEL and Meg-01 cells. Mechanically, TMEA could bind with TPOR protein and further regulate the PI3K/AKT/mTOR/P70S6K and MEK/ERK signal pathways. In vivo, TMEA evidently promoted platelet regeneration in mice with radiation-induced thrombocytopenia but had no effect on Tpor-/- and C57BL/6 (WT) mice. CONCLUSION: TMEA could serve as a novel TPOR agonist to promote MKs differentiation and thrombopoiesis via mTOR and ERK signaling and could potentially be created as a promising new drug to treat thrombocytopenia.

A comprehensive review of Rubia cordifolia L.: Traditional uses, phytochemistry, pharmacological activities, and clinical applications.

Rubia cordifolia (family: Rubiaceae) L (R. cordifolia) is a perennial botanical drug climbing vine. As the main part of the traditional Chinese medicine, the rhizome has a long history. A great number of literary studies have reported that it can be used for the improvement of blood circulation, hemostasis, activation of collaterals, etc. When it comes to the wide application of R. cordifolia in traditional medicine, we systematically review its traditional uses, phytochemistry and pharmacological effects. Literatures were systematically searched using several scientific databases, including China National Knowledge Infrastructure (CNKI), Baidu Scholar, PubMed, Web of Science, and other professional websites. Kew Botanical Garden and the iPlant were used for obtaining the scientific names and plant images of R. cordifolia. In addition, other information was also gathered from books including traditional Chinese herbal medicine, the Chinese Pharmacopoeia, and Chinese Materia Medica. So far, many prescriptions containing R. cordifolia have been widely used in the clinical treatment of abnormal uterine bleeding, primary dysmenorrhea and other gynecological diseases, allergic purpura, renal hemorrhage and other diseases. The phytochemistry studies have reported that more than 100 compounds are found in R. cordifolia, such as bicyclic peptides, terpenes, polysaccharides, trace elements, flavonoids, and quinones. Among them, quinones and peptides are the types of components with the highest contents in R. cordifolia. The modern pharmacological studies have revealed that R. cordifolia and its derived components have anti-tumor, anti-oxidative, anti-platelet aggregation, and anti-inflammatory effects. However, most studies are preclinical. The pharmacological mechanism of R. cordifolia has not been thoroughly studied. In addition, there are few pharmacokinetic and toxicity studies of R. cordifolia, therefore the clinical safety data for R. cordifolia is lacking. To sum up, this review for the first time summarizes a systemic and integrated traditional uses, chemical compositions, pharmacological actions and clinical applications of R. cordifolia, which provides the novel and full-scale insight for the drug development, medicinal value, and application of R. cordifolia in the future.

The Optimal Energy Density of Photobiomodulation Therapy in Decreasing Orthodontic-Related Pain: A Systematic Review and Network Meta-Analysis.

Objective: The aim of this network meta-analysis (NMA) was to explore the optimal energy density (ED) for relief of orthodontic-related pain by photobiomodulation therapy. Background: Orthodontic treatment corrects the deformity of teeth, dental arch, jaw, and face using various orthodontic devices under the action of biomechanics. Materials and methods: A computerized literature search was conducted within the MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases to identify randomized controlled trials (RCTs) that used photobiomodulation therapy to relieve pain during orthodontic treatment. Particular inclusion and exclusion criteria were connected to recognize relevant articles. The information was extricated autonomously by two reviewers, and a quality assessment was carried out by utilizing the Cochrane Collaboration "risk of bias" tool. The RevMan 5.4 software and STATA 15.0 were utilized for data analysis. Also, the NMA was performed with mvmeta commands in Stata (StataCorp, TX). Results: Of the 1024 recognized articles, 21 RCTs were at long last included. Within the risk-of-bias assessments, 2 studies displayed a high risk, 17 an unclear risk, and 2 a low risk. The global and local inconsistency of the NMA in 1 and 2 days was not significant; however, the NMA in 3 days showed a significant inconsistency. Laser with lower ED (0-10 J/cm2) appeared to be the most noteworthy possibility to become the optimal intervention, and it also had the highest mean rank in the rankogram and the biggest value of surface under the cumulative ranking in all three NMA structures. Conclusions: On account of the limited evidence of included trials, laser with lower ED (0-10 J/cm2) appeared to be more valid than the remaining treatment modalities (laser with higher ED, placebo, and control) for pain reduction in 1, 2, and 3 days after orthodontic procedures were applied. In the future, more high-quality research with consistency in research design is needed for further evaluation.

Viability of Photobiomodulaton Therapy in Decreasing Orthodontic-Related Pain: A Systematic Review and Meta-Analysis.

Objective: To assess the viability of photobiomodulation therapy (PBMT) in decreasing orthodontic-related pain after different orthodontic procedures. Methods: A computerized literature search was conducted within the MEDLINE, EMBASE, Scopus, Cochrane Library, Web of Science, CNKI, WanFang, VIP, and CBM databases to identify randomized controlled trials (RCTs), which used PBMT to relieve pain during orthodontic treatment. Particular inclusion and exclusion criteria were connected to recognize relevant articles. The information was extricated autonomously by two reviewers, and a quality assessment was carried out by utilizing the Cochrane Collaboration "risk of bias" tool. Meta-analysis was conducted with fixed- or random-effects models as suitable. Statistical heterogeneity was also examined. The RevMan 5.4 software was utilized for data analysis. Results: Of 1024 recognized articles, 25 RCT were at long last included. Within the risk-of-bias assessments, 1 study displayed a high risk, 22 an unclear risk, and 2 a low risk. The meta-analysis appeared that in patients treated with photobiomodulation (PBM) versus control there was a distinction in support of PBMT in placement of elastomeric separators, canine retraction, and archwire placement during 1 week. Conclusions: PBMT demonstrated to be effective in advancing a reduction pain after elastomeric separators placement, canine retraction, and archwire placement within 1 week. In the future, more high-quality research with consistency in research design is needed for further evaluation.

Celastrol attenuates ischemia/reperfusion-mediated memory dysfunction by downregulating AK005401/MAP3K12.

BACKGROUND: Oxidative stress induces mitochondrial dysfunction, causing memory loss. Long noncoding RNAs influence mitochondrial function and suppress oxidative stress by regulating target protein expression and gene transcription. Celastrol, a natural antioxidant extracted from Tripterygium wilfordii Hook F. ("Thunder of God Vine"), effectively alleviates oxidative stress-mediated tissue injury. In the present study, we examined the effects of celastrol on memory dysfunction induced by ischemia/reperfusion (I/R) and elucidated the mechanisms underlying these effects. METHODS: C57BL/6 mice were used to mimic I/R using the bilateral common carotid clip reperfusion method, and a hippocampal cell line (HT-22) cells were used to establish a model of oxygen-glucose deprivation/reoxygenation (OGD/R). We observed changes in behavior and mitochondrial structure. Cell activity, cell respiration, and antioxidant capacity were measured. MAP3K12, p-JNK, p-c-Jun, p-Akt/Akt, PI3K, Bcl-2, and Bax expression were evaluated. RESULTS: I/R or OGD/R significantly increased AK005401 and MAP3K12 expression, further attenuating PI3K/Akt activation, promoting reactive oxygen species generation and causing mitochondrial dysfunction and cell apoptosis, thereby resulting in memory dysfunction. Celastrol increased antioxidant capacity, inhibited cell apoptosis, and improved mitochondrial function, effectively improving learning and memory by downregulating AK005401 and MAP3K12 and activating PI3K/Akt. CONCLUSIONS: The AK005401/MAP3K12 signaling pathway has an important role in I/R-mediated hippocampal injury, and celastrol can potentially reduce or possibly prevent I/R-induced neuronal injury by downregulating AK005401/MAP3K12 signaling.

Zinc ameliorates human aortic valve calcification through GPR39 mediated ERK1/2 signalling pathway.

AIMS: Calcific aortic valve disease (CAVD) is the most common heart valve disease in the Western world. It has been reported that zinc is accumulated in calcified human aortic valves. However, whether zinc directly regulates CAVD is yet to be elucidated. The present study sought to determine the potential role of zinc in the pathogenesis of CAVD. METHODS AND RESULTS: Using a combination of a human valve interstitial cell (hVIC) calcification model, human aortic valve tissues, and blood samples, we report that 20 µM zinc supplementation attenuates hVIC in vitro calcification, and that this is mediated through inhibition of apoptosis and osteogenic differentiation via the zinc-sensing receptor GPR39-dependent ERK1/2 signalling pathway. Furthermore, we report that GPR39 protein expression is dramatically reduced in calcified human aortic valves, and there is a significant reduction in zinc serum levels in patients with CAVD. Moreover, we reveal that 20 µM zinc treatment prevents the reduction of GPR39 observed in calcified hVICs. We also show that the zinc transporter ZIP13 and ZIP14 are significantly increased in hVICs in response to zinc treatment. Knockdown of ZIP13 or ZIP14 significantly inhibited hVIC in vitro calcification and osteogenic differentiation. CONCLUSIONS: Together, these findings suggest that zinc is a novel inhibitor of CAVD, and report that zinc transporter ZIP13 and ZIP14 are important regulators of hVIC in vitro calcification and osteogenic differentiation. Zinc supplementation may offer a potential therapeutic strategy for CAVD.

Effects of Astragalus membranaceus roots supplementation on growth performance, serum antioxidant and immune response in finishing lambs.

OBJECTIVE: Astragalus membranaceus root is a well-known traditional Chinese herbal medicine with many biological active constituents. This study was conducted to examine the effects of Astragalus membranaceus root powder (AMP) on growth performance, serum antioxidant and immune response in finishing lambs. METHODS: A total of thirty-six Guangling fat-tailed ram lambs (body weight = 19±2 kg, mean ±standard deviation) were randomly assigned to one of six treatments for a 40 d feeding period, with the first 10 d for adaptation. Treatments consisted of the lambs' basal diets with addition of 0, 5, 10, 15, 20, and 30 g/kg of diet of AMP. RESULTS: Response to supplementation level of AMP was quadratic (p≤0.032) for final weight and ADG with the greatest at 10 g/kg of diet, but dry matter intake was not affected (p≥0.227) by treatments. The increase of AMP supplementation resulted in a quadratic response in contents of triglyceride and creatinine (p<0.05), with the lowest values for 10 and 20 g/kg of diet, respectively. A linear and quadratic decrease was observed in activity of alkaline phosphatase in serum of lambs. As the AMP supplementation increased, the activities of total superoxide dismutase and total antioxidant capacity increased linearly (p≤0.018) and hydroxyl radical (OH-) decreased linearly (p = 0.002). For catalase (CAT) and malondialdehyde (MDA), quadratic (p≤0.001) effects were observed among treatments, with the greatest CAT and lowest MDA values at 10 g/kg AMP. Additionally, supplementing AMP up to a level of 10 or 15 g/kg of diet quadratically increased immunoglobulin and interleukin contents in the serum. CONCLUSION: The results indicated that AMP can be used as natural feed additive in the ration of lambs to improve ADG, antioxidant status, and immune functions, and the optimal dose was 10 g/kg of diet under the condition of this experiment.

Activation of AK005401 aggravates acute ischemia/reperfusion mediated hippocampal injury by directly targeting YY1/FGF21.

Ischemia exerts a negative impact on mitochondrial function, which ultimately results in neuronal damage via alterations in gene transcription and protein expression. Long non- coding RNAs (LncRNAs) play pivotal roles in the regulation of target protein expression and gene transcription. In the present study, we observed the effect of an unclassical LncRNA AK005401on ischemia/reperfusion (I/R) ischemia-mediated hippocampal injury and investigated the regulatory role of fibroblast growth factor 21 (FGF21) and Yin Yang 1 (YY1). C57Black/6 mice were subjected to I/R using the bilateral common carotid clip reperfusion method, and AK005401 siRNA oligos were administered via intracerebroventricular injection. HT22 cells were used to establish a model of oxygen-glucose deprivation/reoxygenation (OGD/R). We observed pathological morphology and mitochondrial structure. Neuronal apoptosis was evident. Cell activity, cell respiration, FGF21, YY1, and antioxidant capacity were evaluated. I/R or OGD/R significantly increased the expressions of AK005401and YY1 and decreased FGF21expression, which further attenuated the activation of PI3K/Akt, promoted reactive oxygen species (ROS) generation, and then caused mitochondria dysfunction and cell apoptosis, which were reversed by AK005401 siRNA oligos and were aggravated by overexpression of AK005401 and YY1. We conclude that AK005401/YY1/FGF21 signaling pathway has an important role in I/R-mediated hippocampal injury.

THERMOLUMINESCENCE SPECTRA AND DOSE RESPONSES OF SrSO4 PHOSPHORS DOPED WITH RARE EARTHS (Eu, Dy, Tm) AND PHOSPHORUS.

The thermoluminescence (TL) spectra and dose responses of strontium sulphate doped with rare earth ions show that the SrSO4:Eu2+ phosphor might reasonably be assumed a isoelectronic trap sample which has unique TL characteristics: there is only one obvious glow peak at 385 nm, 489 K in the TL 3D emission spectra and its TL dose response is linear-sublinear. However, there are several elementary glow peaks in the TL 3D emission spectra and their TL dose responses are linear-supralinear for SrSO4:RE3+ (RE = Dy, Tm). These TL peaks occurred from low to high temperature indicate that the traps are distributed in different energy levels. When a suitable amount of other impurities co-doped into these SrSO4:RE3+, such as phosphorus, the relative intensities of these elementary glow peaks are changed significantly, especially the TL peak ~500 K is enhanced while the peaks at lower temperature are suppressed. The enhanced peak of SrSO4:RE3+,P is attributed to the deep traps. Their dose responses remain in nonlinearity when co-doped phosphorus. The above results and the luminescence properties of other sulphate doped rare earths impurities illustrate that the TL characteristics depend on the structure of defect complexes which can be assumed the basic elements in the TL multi-stage processes.

Effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and testicular steroidogenesis-related gene expression of their male kids in Taihang Black Goats.

To investigate the effects of maternal dietary selenium (Se-enriched yeast) on testis development, testosterone level and steroidogenesis-related gene expression in testis of their male kids, selected pregnant Taihang Black Goats were randomly allotted to four treatment groups. They were fed the basal gestation and lactation diets supplemented with 0 (control), 0.5, 2.0 and 4.0 mg of Se/kg DM. Thirty days after weaning, testes were collected from the kids. After the morphological development status of testis was examined, tissue samples were collected for analyzing testosterone concentration and histological parameters. Testosterone synthesis-related genes were detected using real-time PCR. Localization and quantification of androgen receptor (AR) in testis of goats were determined by immunohistochemical and western blot analysis. The results show that Se supplementation in the diet of dams led to higher (p < 0.05) testicular weight, volume, length, width, transverse and vertical grith of their male kids. Excessive Se (4.0 mg/kg) can inhibit the development of testis by decreasing testicular weight and volume. The density of spermatogenic cells and Leydig cells in the Se treatment groups was significantly (p < 0.05) higher than that in the control. Maternal dietary Se did not affect the thickness of testes, thickness of germinal epithelium and diameter of seminiferous tubule. Se supplemented in the diet of dams improved the testosterone level in testis tissue and serum, and promote the expression of testosterone-related genes. The mRNA expression of StAR, 3ß-HSD and CYP11A1 was decreased with the increasing dietary Se levels of dams. Maternal dietary Se can improve the AR protein abundance in testis of their offspring. AR immunopositive product was detected in Leydig cells, peritubular myoid cells, perivascular smooth muscle cells, primary spermatocytes and spermatids. The expression of AR in spermatogenetic cells is stage specific. This study suggests that maternal dietary Se can influence the testis development and spermatogenesis of their male kids by modulating testosterone synthesis in goats. More attention should be given to the potential role of maternal nutrition in improving reproductive performance of their offspring.

Effect of dietary Tartary buckwheat extract supplementation on growth performance, meat quality and antioxidant activity in ewe lambs.

The objective of this study was to investigate the effect of dietary Tartary buckwheat extract (TBE) supplementation on animal growth performance, meat quality and antioxidative activity in the Longissimus thoracis et lumborum muscle of lambs. The results showed that dietary TBE increased body weight, average daily gain, carcass weight, dry matter intake, and digestive organ weight. Dietary TBE had no effect on the pH, color, shear force or intramuscular fat of Longissimus muscle examined, whereas the cooking loss was decreased. The total antioxidative capacity and glutathione peroxidase 4 (GPx4) activity of Longissimus muscle were increased in lambs fed TBE. The mRNA contents of superoxide dismutase, catalase, GPx4 and nuclear factor-like-2 factor (Nrf2) did not vary among the groups, and greater protein levels of GPx4 and Nrf2 were observed. Taken together, these results suggest that TBE can be used as a feed ingredient in lamb production to improve its growth performance, and relieve oxidative stress and increase water holding capacity of meat.

Panax Notoginseng Saponins Ameliorates Coxsackievirus B3-Induced Myocarditis by Activating the Cystathionine-γ-Lyase/Hydrogen Sulfide Pathway.

This study is to determine the therapeutic effects of Panax notoginseng saponins (PNSs) on coxsackievirus B3 (CVB3)-induced myocarditis, and whether cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S) pathway is involved. Mouse model of myocarditis was induced by CVB3 infection, and the mice were subjected to vehicle (saline) or drug treatments (sodium bisulfide (NaHS), propargylglycine (PAG), or PNSs). The results showed that there were inflammatory cell infiltrations, interstitial edemas, and elevated inflammatory cytokines, in CVB3-induced myocarditis. PAG administration increased, whereas NaHS treatment decreased the severity of the myocarditis. PNS treatment dramatically alleviated these myocardial injuries and decreased the viral messenger RNA (mRNA) expression by the enhanced expression of CSE/H2S pathway. Moreover, the therapeutic effects of PNSs on myocarditis were stronger than those of NaHS. Finally, the effect of PNSs on CSE/H2S pathway and cardiac cell protection were verified in cultured cardiac cells. PNSs may be a promising medication for viral myocarditis therapy.

Effects of maternal and dietary selenium (Se-enriched yeast) on the expression of Sel P and apoER2 of germ cells of their offspring in goats.

In this experiment the effect of maternal dietary selenium on the expression of Sel P and apoER2 of goat offspring was studied. The experiment was conducted on 119 Taihang Black Goats randomly divided into 4 groups which were fed with a basal diet, supplemented with 0 (control), 0.5, 2 and 4 mg kg(-1) DM Se. Testis samples were collected from young male of each treatment group at the end of the study (30 d after weaning) for mRNA expression using real-time PCR and for protein expression by immunohistochemistry assay. A significant decrease was observed in mRNA expression of Sel P and apoER2 in the testis of the Se-deficient (Group 1) and the Se-excess (Group 4) compared with that in Groups 2 and 3. A similar trend of the protein expression of Sel P and apoER2 was also found. These data indicate that maternal and dietary selenium has an effect on the expression of Sel P and apoER2 in testis of their offspring. In addition, both groups were similar suggesting that the relationship between Sel P and apoER2, and apoER2 is a receptor of Sel P in the seminiferous epithelium to uptake the selenium.

Effect of high-dose nano-selenium and selenium-yeast on feed digestibility, rumen fermentation, and purine derivatives in sheep.

The aim of this study was to evaluate the effect of nano-selenium (NS) and yeast-selenium (YS) supplementation on feed digestibility, rumen fermentation, and urinary purine derivatives in sheep. Six male ruminally cannulated sheep, average 43.32 ± 4.8 kg of BW, were used in a replicated 3 × 3 Latin square experiment. The treatments were control (without NS and YS), NS with 4 g nano-Se (provide 4 mg Se), and YS with 4 g Se-yeast (provide 4 mg Se) per kilogram of diet dry matter (DM), respectively. Experimental periods were 25 days with 15 days of adaptation and 10 days of sampling. Ruminal pH, ammonia N concentration, molar proportion of propionate, and ratio of acetate to propionate were decreased (P < 0.01), and total ruminal VFA concentration was increased with NS and YS supplementation (P < 0.01). In situ ruminal neutral detergent fiber (aNDF) degradation of Leymus chinensis (P < 0.01) and crude protein (CP) of soybean meal (P < 0.01) were significantly improved by Se supplementation. Digestibilities of DM, organic matter, crude protein, ether extract, aNDF, and ADF in the total tract and urinary excretion of purine derivatives were also affected by feeding Se supplementation diets (P < 0.01). Ruminal fermentation was improved by feeding NS, and feed conversion efficiency was also increased compared with YS (P < 0.01). We concluded that nano-Se can be used as a preferentially available selenium source in ruminant nutrition.

Effects of maternal and dietary selenium (Se-enriched yeast) on the expression of p34(cdc2) and CyclinB1 of germ cells of their offspring in goats.

The aim of the study was to evaluate the effect of selenium on the expression of p34(cdc2) and CyclinB1 (two components of MPF regulating cell cycle) of germ cells of their offspring in goats. A herd of 119 Taihang Black Goats, which was randomly divided into 4 treatments, received experimental diet with different Se levels (from Se-enriched yeast) for 174d. The four treatments, fed with a basal diet, were supplemented with 0 (control), 0.5, 2 and 4 mgkg⁻¹ DM Se. Testis samples were collected from the young male goats of each treatment group at the end of the study (30d after weaning) for mRNA expression using real-time PCR and for protein expression by immunohistochemistry assay. Results show that a significant decrease was observed in mRNA expression of p34(cdc2) and CyclinB1 in the testis of Se-deficient (Group 1) and Se-excess (Group 4) animals compared with that in Groups 2 and 3. However, no significant changes were found in mRNA expression of p34(cdc2) between Se-deficient (Group 1) and Se-excess (Group 4). Also the immunohistochemistry assay detected similar results of protein expression of these two genes. These results suggest, that maternal and dietary Se-induced oxidative stress can modulate the mRNA and protein expression of the cell cycle related genes (p34(cdc2) and CyclinB1) in the testis of their offspring. In addition, Se deficiency and Se excess could prevent the completion of the cell cycle.

Effects of maternal and dietary selenium (Se-enriched yeast) on oxidative status in testis and apoptosis of germ cells during spermatogenesis of their offspring in goats.

To investigate the effect of maternal and dietary selenium on antioxidant status in testis and apoptosis of germ cells during spermatogenesis of their offspring, selected Taihang Black Goats (n=119) were randomly allotted to four treatment groups. They were fed the experimental diet with different Se levels (from Se-enriched yeast) for 174 d from 60 d prior to lactation to weaning of kids. The treatments were: (1) Group 1 (control), basal diet without Se supplementation, (2) Group 2, the same basal diet supplemented 0.5mg Se/kg DM, (3) Group 3, the same basal diet supplemented 2mg Se/kg DM and (4) Group 4, the same basal diet supplemented 4 mg Se/kg DM. Thirty days after weaning, testis samples of the young male goats were collected for mRNA expression and analyzing the antioxidant status and Se concentration, as well as the population of apoptotic germ cells by TUNEL assay. The results show that mRNA expression of apoptosis genes (Bcl-2, Bax and Caspase 8) were significantly higher in Groups 1 and 4 than that in Groups 2 and 3. The same trend was observed in the population of apoptotic cells analyzed by TUNEL assay. GSH-Px activity and Se concentration in testis of offspring was progressively increased with the increasing Se level in diet of dams. However, there was no significant difference in GSH-Px activity between Groups 3 and 4. The lowest MDA content was obtained in Group 2 and a significant decrease was observed in Groups 1, 3 and 4. These data suggest that doe maternal and dietary Se could influence antioxidant status in the testis of their offspring and the oxidative stress related to Se from the dam could modulate mRNA expression of apoptosis genes and apoptosis of germ cells during spermatogenesis. It is possible that Se supplementation of the dam's diet during gestation and lactation could be a way to supply the Se necessary for normal development of reproductive function of their offspring.