Alpiniae oxyphyllae fructus improves production performance and egg quality of laying breeder hens by regulating reproductive hormones, antioxidant function, immunity and intestinal health.

Alpiniae oxyphylla fructus was extensively utilized both as dietary supplements and traditional herbal medicines for healthcare functions and has exhibited a positive impact on animal health. The present study aimed to investigate the effects of Alpiniae oxyphyllae fructus powder (AOP) on production performance, egg quality, egg yolk fatty acid composition, reproductive hormones, antioxidant capacity, immunity, anti-apoptosis ability, and intestinal health in hens. A total of 252 Hainan Wenchang laying hens (30-wk-old) were randomly divided into 3 groups with 6 replicates, a basic diet with 0 (CON), 1 g/kg AOP (AOP1), and 3 g/kg (AOP3) mixed AOP. The AOP supplementation was found to decrease the feed conversion ratio and embryo mortality but to increase the laying rate, average egg weight, and oviduct index linearly (p < 0.05). Furthermore, AOP treatment reduced the total saturated fatty acids and palmitic acid (C16:0) in the egg yolk while increasing eggshell strength, albumen height, and Haugh unit (p < 0.05). The serum levels of albumin and phosphorus were increased, whereas total cholesterol, triglycerides, and glucose levels decreased as a result of AOP treatment (p < 0.05). The inclusion of 3 g/kg AOP had higher 17 ß-estradiol and follicle-stimulating hormone levels in serum, while it up-regulated follicle-stimulating hormone receptor and gonadotropin-releasing hormone expression in ovary (p < 0.05). Dietary AOP strengthened the expression of nuclear factor erythroid2-related factor 2 in ovary and increased the activity of superoxide dismutase and total antioxidant capacity, but had a lower malondialdehyde content in serum (p < 0.05). AOP at 3 g/kg up-regulated superoxide dismutase 1 and heme oxygenase 1 expression in jejunum and ovary (p < 0.05). Meanwhile, AOP supplementation down-regulated p53 expression in ovary and bcl-2-associated x expression in liver and jejunum, especially 3 g/kg of AOP had lower caspase-8 concentrations and down-regulated bcl-2-associated x and caspase-3 expression in ovary (p < 0.05). AOP treatment increased serum levels of immunoglobulin A and immunoglobulin M and upregulated interleukin-4 expression in the liver, while decreasing interleukin-1ß expression in liver and ovary and nod-like receptor protein 3 expression in jejunum (p < 0.05). Dietary AOP increased the ratio of villus height to crypt depth but decreased crypt depth in jejunum, especially when 1 g/kg AOP increased expression levels of occludin, mucin-2, peptide-transporter 1, and sodium glucose cotransporter 1 in jejunum (p < 0.05). AOP treatment altered the composition of the cecal microbial community, as evidenced by increased abundance of Oscillospira and Phascolarctobacterium and reduced richness of Clostridiaceae_Clostridium. Dietary AOP supplementation enriched lipid, amino acid, and propanoate metabolism. Spearman's correlation analysis revealed that the genera Oscillospira, Blautia, and Megasphaera were related to laying performance and intestinal integrity. In brief, supplementation of AOP, especially at 3 g/kg, could improve production performance and egg quality of hens via modulating reproductive hormones, antioxidant capacity, immunity, intestinal barrier, and cecal microbiota. Overall, the present work recommends the dietary inclusion of AOP as a beneficial additive for improving the performance of hens.

Forsythia suspensa polyphenols regulate macrophage M1 polarization to alleviate intestinal inflammation in mice.

BACKGROUND: Inflammatory bowel disease (IBD) was a chronic intestinal disease related to autoimmunity, and its pathogenesis was complex. Forsythia suspensa (F. suspensa) had good anti-inflammatory and antioxidant effects. The active component polyphenols had significant effects in the treatment of intestinal inflammation. Researches had found that polarization, pyroptosis and apoptosis of macrophages can drive the occurrence and development of colitis. PURPOSE: In this study, we examined whether F. suspensa polyphenols (FPP) mitigated DSS-induced colitis, and explored its potential mechanisms. METHODS: The potential targets of F. suspensa in intestinal inflammation were predicted through network pharmacology. Using LPS and IFN-γ induced macrophage M1 polarization in J774A.1 cells. Macrophage polarization was detected through RT-qPCR, flow cytometry and ELISA. Ulcerative colitis (UC) in mice was induced by 2.5% DSS for 7 days, and then oral administrated different doses of FPP for another 7 days. Then we assessed the body weight, diarrhea, bleeding in stool, colon length, cytokines of serum and pathology of colon. The effects of FPP on the gut microbiota in mice also tested and evaluated. RESULTS: Our results showed that the main active ingredient of F. suspensa in protecting intestinal inflammation were polyphenols and F. suspensa was multi-targeted in the treatment of intestinal inflammation. FPP inhibited M1 polarization and polarizes towards M2 in J774A.1 cells. FPP inhibited pyroptosis and apoptosis to exert anti-inflammatory effects. FPP had a good protective effect on DSS induced UC in mice. In unison, FPP inhibited M1 polarization, apoptosis, and pyroptosis in UC mice. FPP regulated intestinal homeostasis in mice with UC by improving the gut microbiota and enhancing the intestinal metabolites short-chain fatty acid (SCFAs). CONCLUSIONS: These data indicated that FPP may alleviate UC by inhibiting M1 polarization in mice. Collectively, these findings suggest that the reduction of colitis by FPP may related to macrophage polarization, pyroptosis and apoptosis.

NIR-II responsive PEGylated MoO2 nanocrystals with LSPR for efficient photothermal and photodynamic performance enhancement.

Phototherapy, including photothermal and photodynamic therapy, has gained extensive attention in the tumor treatment field recently, while synergistic therapy can significantly improve curative effects. However, a complicated photo-responsive nanosystem, different excitation wavelengths, and low tissue depth hindered its actual application. Herein, single near-infrared responsive PEGylated defective MoO2 nanocrystals were fabricated by a green hydrothermal method. The photothermal and photodynamic performances of the samples were presented in detail under a safe power of 1064 nm (NIR-II, 1.0 W cm-2). Interestingly, the photodynamic properties were prompted by the localized surface plasmon resonance (LSPR) photothermal effect obviously, and the collaborative enhancement mechanism was explored in depth. Subsequently, the in vitro cytotoxicity was evaluated on the 4T1 cancer cells under NIR-II irradiation. This work may provide guidance for the facile fabrication of TMOs for NIR-II responsive and enhanced dual-modal phototherapy.

Nano-Zero-Valent Zinc-Modified Municipal Sludge Biochar for Phosphorus Removal.

Municipal sludge biochar (MSBC) can be used to absorb phosphorus in water for waste treatment. Nano-zero-valent zinc (nZVZ) was uniformly attached to MSBC to obtain a highly efficient phosphorus-absorbing composite material, nZVZ-MSBC. Characterization by FTIR, XPS, XRD, and BET showed that nZVZ was uniformly dispersed on the surface of the MSBC. Zinc loading was able to greatly improve the adsorption performance of MSBC for phosphorus. Adsorption experiments illustrated that the adsorption process conformed to the Langmuir model, and the maximum adsorption amount was 186.5 mg/g, which is much higher than that for other municipal sludge biochars. The adsorption process reached 80% of the maximum adsorption capacity at 90 min, and this gradually stabilized after 240 min; adsorption equilibrium was reached within 24 h. The optimum pH for adsorption was 5. The main adsorption mechanism was chemical adsorption, but physical adsorption, external diffusion, internal diffusion, and surface adsorption also played roles. The potential for application as an efficient adsorbent of phosphorus from water was confirmed. In addition, a novel strategy for municipal sludge disposal and resource utilization is provided.

RA-RAR signaling promotes mouse vaginal opening through increasing ß-catenin expression and vaginal epithelial cell apoptosis.

BACKGROUND: Retinoic acid (RA) plays important role in the maintenance and differentiation of the Müllerian ducts during the embryonic stage via RA receptors (RARs). However, the function and mechanism of RA-RAR signaling in the vaginal opening are unknown. METHOD: We used the Rarα knockout mouse model and the wild-type ovariectomized mouse models with subcutaneous injection of RA (2.5 mg/kg) or E2 (0.1 µg/kg) to study the role and mechanism of RA-RAR signaling on the vaginal opening. The effects of Rarα deletion on Ctnnb1 mRNA levels and cell apoptosis in the vaginas were analyzed by real-time PCR and immunofluorescence, respectively. The effects of RA on the expression of ß-catenin and apoptosis in the vaginas were analyzed by real-time PCR and western blotting. The effects of E2 on RA signaling molecules were analyzed by real-time PCR and western blotting. RESULTS: RA signaling molecules were expressed in vaginal epithelial cells, and the mRNA and/or protein levels of RALDH2, RALDH3, RARα and RARγ reached a peak at the time of vaginal opening. The deletion of Rarα resulted in 25.0% of females infertility due to vaginal closure, in which the mRNA (Ctnnb1, Bak and Bax) and protein (Cleaved Caspase-3) levels were significantly decreased, and Bcl2 mRNA levels were significantly increased in the vaginas. The percentage of vaginal epithelium with TUNEL- and Cleaved Caspase-3-positive signals were also significantly decreased in Rarα-/- females with vaginal closure. Furthermore, RA supplementation of ovariectomized wild-type (WT) females significantly increased the expression of ß-catenin, active ß-catenin, BAK and BAX, and significantly decreased BCL2 expression in the vaginas. Thus, the deletion of Rarα prevents vaginal opening by reducing the vaginal ß-catenin expression and epithelial cell apoptosis. The deletion of Rarα also resulted in significant decreases in serum estradiol (E2) and vagina Raldh2/3 mRNA levels. E2 supplementation of ovariectomized WT females significantly increased the expression of RA signaling molecules in the vaginas, suggesting that the up-regulation of RA signaling molecules in the vaginas is dependent on E2 stimulation. CONCLUSION: Taken together, we propose that RA-RAR signaling in the vaginas promotes vaginal opening through increasing ß-catenin expression and vaginal epithelial cell apoptosis.

Mechanism of lead adsorption by a Bacillus cereus strain with indole-3-acetic acid secretion and inorganic phosphorus dissolution functions.

BACKGROUND: Heavy metal pollution has become a major source of environmental pollution because of increasing industrialization. Microbial remediation is a promising approach to remediate lead-contaminated environments owing to its cost-effective, environment-friendly, ecologically sustainable, and highly efficient properties. In this study, the growth-promoting functions and lead-adsorption ability of Bacillus cereus SEM-15 were examined, and the functional mechanism of the strain was preliminarily identified using scanning electron microscopy, energy spectrum, infrared spectrum, and genome analyses, providing theoretical support for utilization of B. cereus SEM-15 in heavy metals remediation. RESULTS: B. cereus SEM-15 showed strong ability to dissolve inorganic phosphorus and secrete indole-3-acetic acid. The lead adsorption efficiency of the strain at lead ion concentration of 150 mg/L was more than 93%. Single factor analysis revealed the optimal conditions for heavy metal adsorption by B. cereus SEM-15 (adsorption time, initial lead ion concentration, pH, and inoculum amount were 10 min, 50-150 mg/L, 6-7, and 5 g/L, respectively) in nutrient-free environment, with the lead adsorption rate reaching 96.58%. Scanning electron microscopy of B. cereus SEM-15 cells before and after lead adsorption showed adherence of a large number of granular precipitates to the cell surface after lead adsorption. X-Ray photoelectron spectroscopy and Fourier transform infrared spectroscopy results indicated the characteristic peaks of Pb-O, Pb-O-R (R = functional group), and Pb-S bonds after lead adsorption, and a shift in the characteristic peaks of bonds and groups related to C, N, and O. Genome annotation results showed the presence of genes related to heavy metals tolerance and plant growth promotion in B. cereus SEM-15, providing a molecular basis for the strain's heavy metals tolerance and plant growth promotion functions. CONCLUSIONS: This study analyzed the lead adsorption characteristics of B. cereus SEM-15 and the associated influencing factors, and discussed the adsorption mechanism and related functional genes, providing a basis for clarifying the underlying molecular mechanism and offering a reference for further research on plant-microorganisms combined remediation of heavy metals polluted environments.

Targeting NMDA receptors in neuropsychiatric disorders by drug screening on human neurons derived from pluripotent stem cells.

NMDA receptors (NMDARs), a prominent subtype of glutamatergic receptors, are implicated in the pathogenesis and development of neuropsychiatric disorders such as epilepsy, intellectual disability, autism spectrum disorder, and schizophrenia, and are therefore a potential therapeutic target in treating these disorders. Neurons derived from induced pluripotent stem cells (iPSCs) have provided the opportunity to investigate human NMDARs in their native environment. In this review, we describe the expression, function, and regulation of NMDARs in human iPSC-derived neurons and discuss approaches for utilizing human neurons for identifying potential drugs that target NMDARs in the treatment of neuropsychiatric disorders. A challenge in studying NMDARs in human iPSC-derived neurons is a predominance of those receptors containing the GluN2B subunit and low synaptic expression, suggesting a relatively immature phenotype of these neurons and delayed development of functional NMDARs. We outline potential approaches for improving neuronal maturation of human iPSC-derived neurons and accelerating the functional expression of NMDARs. Acceleration of functional expression of NMDARs in human iPSC-derived neurons will improve the modeling of neuropsychiatric disorders and facilitate the discovery and development of novel therapeutics targeting NMDARs for the treatment of these disorders.

Dioscin potentiates the antitumor effect of suicide gene therapy in melanoma by gap junction intercellular communication-mediated antigen cross-presentation.

Dioscin (Dio), steroid saponin, exists in several medicinal herbs with potent anticancer efficacy. This study aimed to explore the effect of Dio on the immune-related modulation and synergistic therapeutic effects of the herpes simplex virus thymidine kinase/ganciclovir (HSV-Tk/GCV) suicide gene therapy system in murine melanoma, thereby providing a research basis to improve the potential immunomodulatory mechanism underlying combination therapy. Using both in vitro and in vivo experiments, we confirmed the immunocidal effect of Dio-potentiated suicide gene therapy on melanoma. The results showed that Dio upregulated connexin 43 (Cx43) expression and improved gap junction intercellular communication (GJIC) in B16 cells while increasing the cross-presentation of antigens by dendritic cells (DCs), eventually promoting the activation and antitumor immune killing effects of CD8+ T lymphocytes. In contrast, inhibition or blockade of the GJIC function (overexpression of mutant Cx43 tumor cells/Gap26) partially reversed the potentiating effect. The significant synergistic effect of Dio on HSV-Tk/GCV suicide gene therapy was further investigated in a B16 xenograft mouse model. The increased number and activation ratio of CD8+ T lymphocytes and the levels of Gzms-B, IFN-γ, and TNF-α in mice reconfirmed the potential modulatory effects of Dio on the immune system. Taken together, Dio targets Cx43 to enhance GJIC function, improve the antigens cross-presentation of DCs, and activate the antitumor immune effect of CD8+ T lymphocytes, thereby providing insights into the potential immunomodulatory mechanism underlying combination therapy.

Protective effect of Qingre Huoxue decoction against myocardial infarction via PI3K/Akt autophagy pathway based on UPLC-MS, network pharmacology, and in vivo evidence.

CONTEXT: Qingre Huoxue (QRHX) decoction, a traditional Chinese medicine, has been widely used to prevent and treat myocardial infarction (MI). OBJECTIVE: This study elucidates the possible mechanisms of QRHX in preventing or treating MI in a rat model. MATERIALS AND METHODS: The chemical constituents of QRHX were identified by UPLC-MS. Sprague-Dawley rats were randomly divided into the Sham (normal saline), Model (normal saline), QRHX-L, QRHX-M and QRHX-H group (n = 10 per group). QRHX decoction was administered by gavage to the rats for 14 days (5, 10 and 20 g/kg/day). The left anterior descending ligation method was performed to develop MI in Model and QRHX groups, and the same surgical procedures excluding ligation sutures were performed for the sham group. Finally, we evaluated cardiac function, myocardial fibrosis degree, serum inflammatory factors, autophagy levels and verified the signalling pathways in vivo. RESULTS: A total of 68 active components of QRHX corresponding to 223 active targets were obtained and 2558 MI-related disease targets were collected. After integration, 123 QRHX anti-MI targets were obtained, and 70 signalling pathways, such as PI3K/Akt, were identified by enrichment analysis. In vivo experiments suggest that QRHX could reduce the degree of myocardial fibrosis, downregulate serum inflammatory factors, and promote autophagy in MI rats. DISCUSSION AND CONCLUSIONS: QRHX plays a protective role in the myocardium by mediating PI3K/Akt signalling pathway to activate autophagy and inhibiting inflammatory factor expression. These findings provide a scientific basis for further research and validation of QRHX as a potential therapeutic for MI.

Environmental performance of blue foods.

Fish and other aquatic foods (blue foods) present an opportunity for more sustainable diets1,2. Yet comprehensive comparison has been limited due to sparse inclusion of blue foods in environmental impact studies3,4 relative to the vast diversity of production5. Here we provide standardized estimates of greenhouse gas, nitrogen, phosphorus, freshwater and land stressors for species groups covering nearly three quarters of global production. We find that across all blue foods, farmed bivalves and seaweeds generate the lowest stressors. Capture fisheries predominantly generate greenhouse gas emissions, with small pelagic fishes generating lower emissions than all fed aquaculture, but flatfish and crustaceans generating the highest. Among farmed finfish and crustaceans, silver and bighead carps have the lowest greenhouse gas, nitrogen and phosphorus emissions, but highest water use, while farmed salmon and trout use the least land and water. Finally, we model intervention scenarios and find improving feed conversion ratios reduces stressors across all fed groups, increasing fish yield reduces land and water use by up to half, and optimizing gears reduces capture fishery emissions by more than half for some groups. Collectively, our analysis identifies high-performing blue foods, highlights opportunities to improve environmental performance, advances data-poor environmental assessments, and informs sustainable diets.

The Protective Effects of Maresin 1 in the OVA-Induced Asthma Mouse Model.

Asthma is a chronic inflammatory disease that cannot be cured. Maresin 1 (MaR1) is a specific lipid synthesized by macrophages that exhibits powerful anti-inflammatory effects in various inflammatory diseases. The goal of this study was to evaluate the effect of MaR1 on allergic asthma using an ovalbumin- (OVA-) induced asthma model. Thirty BALB/c mice were randomly allocated to control, OVA, and MaR1 + OVA groups. Mice were sacrificed 24 hours after the end of the last challenge, and serum, bronchoalveolar lavage fluid (BALF), and lung tissue were collected for further analysis. Western blotting was used to measure the protein level of IκBα, the activation of the NF-κB signaling pathway, and the expression of NF-κB downstream inflammatory cytokines. Quantitative real-time polymerase chain reactions (qRT-PCRs) were used to evaluate the expression levels of COX-2 and ICAM-1 in lung tissues. We found that high doses of MaR1 were most effective in preventing OVA-induced inflammatory cell infiltration and excessive mucus production in lung tissue, reducing the number of inflammatory cells in the BALF and inhibiting the expression of serum or BALF-associated inflammatory factors. Furthermore, high-dose MaR1 treatment markedly suppressed the activation of the NF-κB signaling pathway, the degradation of IκBα, and the expression of inflammatory genes downstream of NF-κB, such as COX-2 and ICAM-1, in the OVA-induced asthma mouse model. Our findings indicate that MaR1 may play a critical role in OVA-induced asthma and may be therapeutically useful for the management of asthma.

Semi-interpenetrating polymer networks prepared from castor oil-based waterborne polyurethanes and carboxymethyl chitosan.

A series of vegetable oil-based waterborne polyurethane composites were prepared through construction of novel semi-interpenetrating polymers network using carboxymethyl chitosan (CA) as the secondary polymer phase. The effects of CA contents on storage stability, and particle size distribution of the composite dispersions and thermal stability, mechanical properties and surface wettability of composite films were investigated and discussed. The results showed that the composite dispersions displayed excellent storage stability and the biomass contents of resulting films were high up to 80 %. A significant increase in crosslinking density and glass transition temperature of the composite films were observed as the CA contents increased, which was attributed to the increasing hard segment of films and strong hydrogen bonding interaction between polyurethanes and CA. This work provided a simple method to tailor the performance of environmentally friendly vegetable oil-based waterborne polyurethane, which could find application in the field of coatings, adhesives, ink and so on.

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity.

Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.

Surgical effect and electrophysiological study of patients with hemifacial spasm treated with botulinum toxin or acupuncture before microvascular decompression.

OBJECTIVE: We investigated patients with hemifacial spasm (HFS) who received a botulinum toxin (BT) injection or acupuncture before receiving microvascular decompression (MVD) to determine whether it affects the success rate of surgery. Abnormal Muscle Response (AMR) and Compound Motor Action Potential (CMAP) are commonly used as electrophysiological monitoring methods in surgery, and we will compare the differences between these patients in this regard. PATIENTS AND METHODS: A total of 539 patients with HFS underwent MVD treatment in our department between January 2014 and June 2017. Among them, 83 patients had received BT injection before surgery and were recorded as BT group. Eighty-three patients underwent acupuncture before surgery and were recorded as acupuncture group. Five patients received both BT injection and acupuncture before surgery and were recorded as mixed group. A total of 368 patients who had not received any treatment before surgery were recorded as simple MVD group. We calculated the immediate and long-term remission rates after surgery. AMR and CMAP monitoring were routinely performed during surgery. RESULTS: Immediate remission rate after surgery was 96.4% (80/83) in BT group, 100% (83/83) in acupuncture group, 100% (5/5) in mixed group, and 95.1% (350/368) in simple MVD group, and the immediate remission rate of BT group is significantly higher than that of simple MVD group (p = 0.04). Long-term remission rate: the remission rates of the four groups were 94.0% (78/83), 97.6% (81/83), 100.0% (5/5) and 92.7%(341/368), respectively, and there is no statistical difference between them (p > 0.05). The amplitude of one branch or several branches of CMAP on the affected side was lower than the healthy side in BT or acupuncture treatment patients. CONCLUSIONS: A preoperative BT injection or acupuncture treatment do not reduce the postoperative remission rate of HFS patients treated with MVD, and the amplitude of CMAP on the affected side was lower than the healthy side.

Compound shuanghua tablets combined with Western medicine on serum and secretion inflammatory factors in patients with acute secretory otitis media caused by swimming.

To observe and analyze the effect of compound shuanghua tablets combined with western medicine on serum and secretion inflammatory factors in patients with acute secretory otitis media caused by swimming. The 140 patients who had been treated in our hospital for acute secretory otitis media were selected as research objects, all of which were caused by swimming. The patients were divided into two groups, namely the control group accepting routine western drug therapy and the research group accepting compound shuanghua tablets combined with western drug therapy, each group contains 70 patients. The therapeutic effect of patients in two groups were observed and compared. Through observation, the levels of tumor necrosis factor, interleukin-6 and interleukin-10 were found to be significantly improved in the research group compared with the control group, and the intergroup difference was of statistical significance, p<0.05; The overall treatment efficiency of the research group was significantly higher than that of the control group, with statistical significance, p<0.05. For patients with acute secretory otitis media caused by swimming, the compound shuanghua tablets combined with Western medicine treatment can not only actively reduce various inflammatory factors in middle ear effusion, but also significantly improve the overall treatment efficiency.

Flavonoids of Rosa roxburghii Tratt exhibit radioprotection and anti-apoptosis properties via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway.

The objective of our study was to assess the radioprotective effect of flavonoids extracted from Rosa roxburghii Tratt (FRT) and investigate the role of Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in radiation-induced apoptosis. Cells and mice were exposed to (60)Co γ-rays at a dose of 6 Gy. The radiation treatment induced significant effects on tissue pathological changes, apoptosis, Ca(2+), ROS, DNA damage, and expression levels of Bcl-2, Caspase-3 (C-Caspase-3), and PARP-1. The results showed that FRT acted as an antioxidant, reduced DNA damage, corrected the pathological changes of the tissue induced by radiation, promoted the formation of spleen nodules, resisted sperm aberration, and protected the thymus. FRT significantly reduced cell apoptosis compared with the irradiation group. The expression of Ca(2+) and C-Caspase-3 was decreased after FRT treatment compared with the radiation-treated group. At the same time, expression of prototype PARP-1 and Bcl-2 increased, leading to a decrease in the percentage of apoptosis cells in FRT treatment groups. We conclude that FRT acts as a radioprotector. Apoptosis signals were activated via the Bcl-2(Ca(2+))/Caspase-3/PARP-1 pathway in irradiated cells and FRT inhibited this pathway of apoptosis by down-regulation of C-Caspase-3 and Ca(2+) and up-regulation of prototype PARP-1 and Bcl-2.

Flavonoids of Rosa roxburghii Tratt act as radioprotectors.

BACKGROUND: To study the radioprotective effects of flavonoids from Rosa roxburghii Tratt (FRT). MATERIALS AND METHODS: The radioprotective effects of FRT were investigated by examining cell viability, 30-day survival of mice and the number of colony-forming units in spleen (CFU-S) after total-body 60Co irradiation. RESULTS: The survival rates of irradiated cells gradually increased with increasing concentrations of FRT. The survival rate was the highest at 87% with a concentration of 30 µg/mL. Pretreatment with FRT was needed to realize its radioprotective activity in mice at the dose of 60 mg/kg. With the increasing doses of 30 mg/kg, 60 mg/kg and 120 mg/kg, the numbers of CFU-S increased, and were significantly different compared with the control group. CONCLUSIONS: Pretreatment with FRT prior to irradiation resulted in significantly higher cell survival at 24 h after 5 Gy radiation, increased 30-day survival in mice after exposure to a potentially lethal dose of 8 Gy, and resulted in a higher number of CFU-S in mice after exposure to a dose of 6 Gy. These results collectively indicate that FRT is an effective radioprotective agent.

Ligustrazine improves atherosclerosis in rat via attenuation of oxidative stress.

CONTEXT: Ligustrazine (Lig) is a compound isolated from the rhizome of Ligusticum chuanxiong Hort. (Umbelliferae) and has been reported to be effective for the treatment of a variety of vascular diseases. OBJECTIVE: The anti-atherosclerotic activities of Lig are evaluated in vivo for the first time in the present study. MATERIALS AND METHODS: We gave rats a single injection of vitamin D3 and then fed them with an atherogenic diet for 6 weeks to induce atherosclerosis. Lig was simultaneously given to rats by gavage at the dose of 20 or 80 mg/kg in the therapy groups. Multiple approaches including spectrophotometry, hematoxylin and eosin (H&E) staining, and quantitative RT-PCR were applied to investigate the effects of Lig on blood parameters, aorta and liver histology, and gene expression. In addition, the solely effects of Lig on food intake, body weight gain, and taste preference were also evaluated. RESULTS: We found that two doses of Lig treatment decreased the total cholesterol levels by 65.2 and 76.7%, respectively, in the plasma. Triglyceride (by 53.2 and 77.9%) and low-density lipoprotein (by 71.2 and 79.0%) levels were also decreased. However, high-density lipoprotein level was slightly increased. The circulating endothelial cells were decreased by 42.2 and 60.0% in Lig-treated rats, indicating the attenuation of endothelial injury. In contrast, Lig restored the total antioxidant capacity and superoxide dismutase 1 (SOD1) activity while decreasing the MDA generation. Furthermore, Lig improved liver dysfunction by decreasing ALT (by 13.0 and 49.7%) and AST (by 10.7 and 14.3%) levels. Histological examinations revealed that Lig suppressed atherosclerotic plaque progression in the thoracic aorta and lipid accumulation in the liver. At the transcriptional level, Lig inhibited the induction of antioxidant genes both in aorta and in liver. Lig also suppressed the mRNA expression of the genes involved in the hepatic fatty acid oxidation. Finally, Lig had a minimum effect on food intake, body weight gain, and taste preference. DISCUSSION AND CONCLUSION: Our results suggest that Lig suppresses the development of atherosclerosis and hepatic lipid accumulation via the alleviation of oxidative stress and the improvement of dyslipidemia.

Changes of plasma glutamine concentration and hepatocyte membrane system N transporters expression in early endotoxemia.

BACKGROUND: Glutamine plays important roles in health and critical illness. During endotoxemia, glutamine metabolism, including its plasma level and transport, changes markedly. Previous studies have demonstrated that system N transporters in hepatocytes play a major role in hepatic glutamine transport. However, little is known about the changes of mRNA and protein expression of system N transporters in hepatocyte plasma membrane. Furthermore, the alteration of plasma glutamine concentration during endotoxemia is still controversial. In this study, we investigated the changes in early endotoxemic rats by intraperitoneal injection of lipopolysaccharide (LPS). MATERIALS AND METHODS: Three, 6, 12 mg/kg body weight doses of LPS were injected intraperitoneally to establish the endotoxemic rat model; equal volume of 0.9% saline was used as the control. Before and 2, 4, 6, 12, 24h after injections, plasma glutamine concentration, mRNA, and protein expression of SNAT3 and SNAT5 transporters in hepatocyte plasma membrane were detected by high performance liquid chromatography, real-time PCR, and Western blot, respectively. RESULTS: LPS injection resulted in a marked increase of the plasma glutamine concentration from 4 to 12h (3mg/kg) and 2 to 6h (6 mg/kg, 12 mg/kg) after the injection compared with its physiologic level, and a significant decrease in 6, 12 mg/kg groups at 24h. Both the mRNA and protein expression of SNAT3 and SNAT5 were enhanced by LPS in a time- and dose-dependent manner. CONCLUSIONS: The plasma glutamine concentration in endotoxemic rat increased transiently during early endotoxemia but subsequently decreased over time. The effect of LPS on system N expression occurs not only at the protein level, but also at the mRNA level. It is reasonable to supplement glutamine for patients with sepsis or endotoxemia begin at 6 to 12h after the development of disease.

Preoperative 3T high field blood oxygen level dependent functional magnetic resonance imaging for glioma involving sensory cortical areas.

BACKGROUND: Localization of sensory cortical areas during the operation is essential to preserve the sensory function. Intraoperative direct electrostimulation under awake anesthesia is the golden standard but time-consuming. We applied 3T high field blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to identify the relationship between glioma and cortical sensory areas preoperatively and to guide intraoperative direct electrostimulation for quick and precise localization. METHODS: Five glioma patients with sensory cortex involvement by or next to the lesion had preoperative BOLD fMRI to determine the spatial relationship of cortical sensory areas to the tumours. Bilateral hand opposite movement was performed by these patients for fMRI. Precentral and postcentral gyri were identified by electrical stimulation during the operation. Karnofsky Performance Status scores of the patients' pre- and postoperative and the role of BOLD fMRI were evaluated. RESULTS: The cortical sensory areas were all activated in five glioma patients involving postcentral gyrus areas by BOLD fMRI with bilateral hand opposite movement. The detected activation areas corresponded with the results from cortical electrical stimulation. CONCLUSIONS: The relationship between cortical sensory areas and tumour can be accurately shown by BOLD fMRI before operation. And the information used to make the tumour resection could obtain good clinical results.