Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

Zerumbone ameliorates the inflammatory response and organ damage in severe acute pancreatitis via the ROS/NF-κB pathway.

OBJECTIVE: The aim of the current study was to determine the mechanism by which Zerumbone (ZER) ameliorates inflammation and organ damage in a rat model of severe acute pancreatitis (SAP). METHODS: Different concentrations of ZER (10, 20 and 40 mg/kg) were administered by femoral vein puncture 30 min prior to establishment of the SAP model. Hematoxylin and eosin (H&E) staining was used to assess pathological changes in the pancreatic tissue of SAP-induced rats. The lung wet/dry (W/D) ratio was assessed and serum levels of amylase (AMY), alanine aminotransferase (ALT), creatinine (Cr), aspartate aminotransferase (AST) and phospholipase A2 (PLA2) were measured. Western blot analysis was used to examine changes in the expression of ROS/NF-κB pathway-associated proteins. RESULTS: SAP was confirmed by significant histopathological damage to the pancreas. ZER (10, 20 and 40 mg/kg) was found to alleviate pancreatitis and decrease ascites volume, lung W/D ratio, pancreatic pathology score, oxidative stress and inflammatory damage. High concentrations (20 and 40 mg/kg) of ZER were shown to increase levels of hepatorenal toxicity. In contrast, 10 mg/kg ZER was found to attenuate liver enzyme levels, reduce pathological damage to the liver, and protect against extrapancreatic organ damage to the liver in SAP-induced rats. Moreover, ZER showed no significant side effects in normal rats. Finally, we demonstrated that ZER mediated its anti-inflammatory effects on SAP through the ROS/NF-κB signaling pathway. CONCLUSION: ZER alleviated SAP-induced oxidative stress and inflammatory injury via the ROS/NF-κB pathway, and had a protective effect on lung injury and liver damage.

Oxidation of tetracycline hydrochloride with a photoenhanced MIL-101(Fe)/g-C3N4/PMS system: Synergetic effects and radical/nonradical pathways.

MIL-101(Fe)-based catalysts have been widely used for degradation of organic pollutants based on peroxymonosulfate (PMS) activation. Hence, a facile calcination and hydrothermal method was used in this study to prepare a MIL-101(Fe)/g-C3N4 composite catalyst with high activity and high stability for PMS activation to degrade tetracycline hydrochloride (TC) under visible-light irradiation. We clearly elucidated the mechanism involved in the MIL-101(Fe)/g-C3N4 photo Fenton-catalyzed PMS activation process by separating the PMS activation and pollutant oxidation processes. The synergetic effects of MIL-101(Fe) and g-C3N4 involved MIL-101(Fe) acting as an electron shuttle mediating electron transfer from the organic substrate to PMS, accompanied by redox cycling of the surface Fe(II)/Fe(III). Multiple experimental results indicated that PMS was bound to the surface of MIL-101(Fe)/g-C3N4 during visible irradiation and generation of sulfate radicals (SO4•-), hydroxyl radicals (•OH) and superoxide anion free radicals (•O2-) for the radical pathway and singlet oxygen (1O2) and holes (h+) for the nonradical pathway. The major degradation pathways for TC can be described as demethylation, deamination, deamidation and carbonylation. This work provides valuable information and advances the fundamental understanding needed for design and syntheses of metal-free conjugated polymers modified by metal-organic frameworks for heterogeneous photo-Fenton reactions.

Development of a MOF-based SPE method combined with GC-MS for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil.

In this work, a rapid, highly selective, reusable and effective method was developed for simultaneous determination of alachlor, acetochlor and pretilachlor in field soil by GC-MS coupled with MIL-101 based SPE. Main factors affecting the SPE by using MIL-101 were optimized. Moreover, by comparing with the other commercial materials such as C18, PSA and Florisil, the MIL-101(Cr) exhibited excellent adsorption performance, which aimed at amide herbicides. On the other hand, method validation displayed excellent method performance, achieving good linearities with r2 ≥ 0.9921, limits of detection between 0.25-0.45 µg kg-1, enrichment factors ≥ 89, matrix effect in the range of ± 20%, recoveries between 86.3% and 102.4%, and RSD lower than 4.38%. The developed method was successfully applied to the determination of amide herbicides in soil taken from the wheat, corn and soybean field at different depths, where the concentration of alachlor, acetochlor and pretilachlor were in the range of 0.62-8.04 µg kg-1. It was demonstrated that the more depth of soil, the lower of three amide herbicides. This finding could be proposed a novel method to detect the amide herbicides in the agriculture and food industry.

A rapid and environmentally friendly method for determination of parabens preservatives in flavors by supercritical fluid chromatography-tandem mass spectrometry.

A rapid method for determination of parabens preservatives (methyl paraben, ethyl paraben, isopropyl paraben, propyl paraben, isobutyl paraben, and butyl paraben) in flavors was established by using supercritical fluid chromatography-tandem mass spectrometry combined with dispersive solid-phase extraction. After adding methanol and primary secondary amine to the sample simultaneously, high extraction efficiency and good sample cleanup could be obtained by simple shaking. Parabens were well separated on a Chiralpak IG-3 column in 6 min by gradient elution. Recoveries from spiked blank samples at 0.5, 1.0, and 5.0 mg/kg were determined to be 88.3-106.6%with relative standard deviations less than 8.0%. All analytes achieved good linear relation (r ≥ 0.999 2). The limits of detection for all analytes ranged from 0.03 to 0.09 mg/kg and the limits of quantification from 0.11 to 0.31 mg/kg, respectively. A total of 20 actual samples were successfully analyzed by taking the proposed method. Being simple, rapid, green, and reliable, this method can be taken for the determination of parabens preservatives in flavors.

Valproic acid counteracts polycyclic aromatic hydrocarbons (PAHs)-induced tumorigenic effects by regulating the polarization of macrophages.

Polycyclic aromatic hydrocarbons (PAHs) are common persistent organic pollutants that are carcinogenic, teratogenic and mutagenic, causing a variety of harm to human health. In this study, we investigated the mechanism of how valproic acid (VPA) interferes with the carcinogenesis of PAHs protect normal tissues via the regulation of macrophages' function. Using the established model of transformed malignant breast cancer by 7,12-dimethylbenz[a]anthracene (DMBA), a representative PAH carcinogen, we discovered VPA induces the polarization of macrophages toward the M1 phenotype in the tumor tissues, facilitates the expression of pro-inflammatory cytokines such as IFN-γ, IL-12 and TNF-α, activates CD8+ T cells to secret Granzyme B thus to promote the apoptosis of tumor cells and suppresses the viability of vascular endothelial cells in tissue stroma of tumor. Surprisingly, VPA selectively induces macrophages to polarize towards the M2 phenotype in normal tissues and promotes the expression of anti-inflammatory cytokines such as IL-10 to enhance cell proliferation. Additionally, at the cellular level, VPA can directly regulate the polarization of macrophages to affect the growth of vascular endothelial cells by simulating the living conditions of tumor and normal cells. Collectively, VPA exerts an interventional effect on tumor growth and a protective effect on normal tissues by regulation of selective macrophages' polarization in their microenvironment.

A New Highly Oxygenated Polyketide Derivative from Trichoderma sp. and Its Antifungal Activity.

A new highly oxygenated polyketide derivative, trichodersine (1), together with fourteen known compounds (2-15) were isolated from Trichoderma sp. MWTGP-04. The structure of trichodersine (1) was established based on comprehensive spectroscopic data analysis, and biogenesis argument. The results of double culture experiments indicated that the strain exhibited potential antifungal activity. The antifungal activities of all isolated compounds were evaluated, among them compound 1 exhibited remarkable antifungal activities against Fusarium solani, Plectosphaerella cucumerina, Alternaria panax, and Aspergillus niger, with minimum inhibitory concentrations (MICs) of 4, 4, 16, and 32 µg/mL, respectively. In addition, the antifungal experiments of polyketide derivatives (1-3) disclosed that their degree of oxidation was a key factor affecting the antifungal activity.

Altered gut microbiome accompanying with placenta barrier dysfunction programs pregnant complications in mice caused by graphene oxide.

The wide use of graphene oxide (GO) has raised increasing concerns about the potential risks to environmental and human health. Recent studies have shown the vital role of gut microbiome in various pathological status or even exogenous exposure, but more detailed understanding about the effects of possible gut microbiome alterations under GO exposure on reproductive toxicology evaluations in pregnant mammals remained elusive. Here we found that orally administrated GO daily during gestational day (GD) 7-16 caused dose-dependent pregnant complications of mice on the endpoint (GD19), including decreased weight of dam and live fetus, high rate of resorbed embryos and dead fetus, and skeletal development retardation. Meanwhile in placenta tissues of pregnant mice exposed to GO at dose over 10 mg/kg, the expression levels of tight junctions (Claudin1 and Occludin) and vascular endothelial growth factor (VEGFA) decreased approximately by 30%-80%, meaning impaired placenta barrier. According to the data of fecal 16s RNA sequencing in 40 mg/kg dose group and the control group, gut microbiome showed dramatically decreased α- and ß-diversity, and upregulated Firmicutes/Bacteroidetes ratio owing to GO exposure. What's more, significantly differentiated abundance of Euryarchaeota is expected to be a special biomarker for failed pregnancy caused by GO. Notably, the result of Spearman correlation analysis suggested that there was a strong link (correlation coefficient>0.6) between perturbed gut microbiome with both abnormally expressed factors of placenta barrier and adverse pregnant outcomes. In summary, the damages of GO exposure to placenta barrier and pregnancy were dose-dependent. And GO exposure was responsible for gut microbiome dysbiosis in mice with pregnant complications. These findings could provide referable evidence to evaluate reproductive risk of GO to mammals.

Ablation of glutaredoxin 1 promotes pulmonary angiogenesis and alveolar formation in hyperoxia-injured lungs by modifying HIF-1α stability and inhibiting the NF-κB pathway.

Glutaredoxin 1 (Grx1) is an important thiol transferase that catalyses the deglutathionylation of proteins through its active site. Deletion of Grx1 increases levels of glutathione-protein adducts and improves ischaemic revascularization. In this study, we investigated whether the absence of Grx1 ameliorates pathological changes in blood vessels and alveoli in a mouse model exposed to hyperoxic conditions. High oxygen exposure for three consecutive weeks increased the levels of Grx1 in the lungs of hyperoxic mice from control levels, while Grx1 levels in Grx1 knockout (KO) mice were significantly reduced under high oxygen conditions. Exposure to 85% oxygen for 21 days reduced alveolarization in wild-type (WT) mice but increased the numbers of alveoli and the survival rate of Grx1 KO littermates. Importantly, vascular endothelial growth factor receptor 2 (VEGFR2) and vascular endothelial growth factor A (VEGFA) expressions were increased in Grx1 KO mice after hyperoxia treatment, and these effects were probably attributable to increased hypoxia-inducible factor (HIF)-1α expression. On the other hand, in response to nuclear factor (NF)-κB inhibition by Grx1 ablation, chemokine and caspase-3 levels were reduced, although the Bcl-2:Bax ratio was increased. Here, we provide evidence that Grx1 plays an important role in regulating pathological damage under hyperoxic conditions by promoting HIF-1α stability and inhibiting the NF-κB pathway in vivo. Our study highlights the functional importance of the Grx1/protein S-glutathionylation (PSSG) redox module in the regulation of ischaemic revascularization, indicating potential clinical and therapeutic applications.

Heparinized silk fibroin hydrogels loading FGF1 promote the wound healing in rats with full-thickness skin excision.

BACKGROUND: Silk fibroin hydrogel, derived from Bombyx mori cocoons, has been shown to have potential effects on wound healing due to its excellent biocompatibility and less immunogenic and biodegradable properties. Many studies suggest silk fibroin as a promising material of wound dressing and it can support the adhesion and proliferation of a variety of human cells in vitro. However, lack of translational evidence has hampered its clinical applications for skin repair. Herein, a heparin-immobilized fibroin hydrogel was fabricated to deliver FGF1 (human acidic fibroblast growth factor 1) on top of wound in rats with full-thickness skin excision by performing comprehensive preclinical studies to fully evaluate its safety and effectiveness. The wound-healing efficiency of developed fibroin hydrogels was evaluated in full-thickness wound model of rats, compared with the chitosan used clinically. RESULTS: The water absorption, swelling ratio, accumulative FGF1 releasing rate and biodegradation ratio of fabricated hydrogels were measured. The regenerated fibroin hydrogels with good water uptake properties rapidly swelled to a 17.3-fold maximum swelling behavior over 12 h and a total amount of 40.48 ± 1.28% hydrogels was lost within 15 days. Furthermore, accumulative releasing data suggested that heparinized hydrogels possessed effective release behavior of FGF1. Then full-thickness skin excision was created in rats and left untreated or covered with heparinized fibroin hydrogels-immobilized recombinant human FGF1. The histological evaluation using hematoxylin and eosin (HE) and Masson's trichrome (MT) staining was performed to observe the dermic formation and collagen deposition on the wound-healing site. To evaluate the wound-healing mechanisms induced by fibroin hydrogel treatment, wound-healing scratch and cell proliferation assay were performed. it was found that both fibroin hydrogels and FGF1 can facilitate the migration of fibroblast L929 cells proliferation and migration. CONCLUSION: This study provides systematic preclinical evidence that the silk fibroin promotes wound healing as a wound-healing dressing, thereby establishing a foundation toward its further application for new treatment options of wound repair and regeneration.

Three new sesquiterpenes from the stems of Nicotiana tabacum and their bioactivities.

Three new sesquiterpenes, methyl 4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (1), methyl 2-hydroxy-4-isopropyl-7-methoxy-6-methylnaphthalene-1-carboxylate (2), and methyl 2-hydroxy-6-(hydroxymethyl)-4-isopropyl-7-methoxynaphthalene-1-carboxylate (3), together with three known sesquiterpenes (4-6), were isolated from the stems of Nicotiana tabacum. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. The results showed that compounds 2, 3, and 5 exhibited high anti-TMV activity with inhibition rates of 33.6, 35.8, and 36.7%. Compounds 1-6 showed weak inhibitory activities against some tested human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) with IC50 values in the range of 6.7-9.6 µM.

[A new isobenzofuranone derivative from Phlomis betonicoides and its antibacterial activity].

A new isobenzofuranone derivative has been isolated from Phlomis betonicoides by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compound was determined as 5-(3-hydroxypropyl)-2,2-dimethyl-2H-furo[3,4-h]chromen-7(9H)-one (1) by NMR, MS, IR and UV spectroscopic data. Compound 1 showed potent antibacterial activity with an MIC90 value of (58.4 ± 4.2) mg·L⁻¹ for methicillin resistant Staphylococcus aureus (MRSA) strain [levofloxacin as a control with MIC90 value of (52.8±4.6) mg·L⁻¹].

Three new benzolactones from Lavandula angustifolia and their bioactivities.

Three new benzolactones (1-3), together with four known ones (4-7), were isolated from the whole herb of Lavandula angustifolia. Their structures were established on the basis of detailed spectroscopic analysis (1D- and 2D-NMR, HRESIMS, UV, and IR) and comparison with data reported in the literature. New compounds were evaluated for their anti-tobacco mosaic virus (TMV) activities and cytotoxic activities. The results revealed that compounds 1-3 showed obvious anti-TMV activities with inhibition rates of 26.9, 30.2, and 28.4%, which were at the same grade as positive control. Compounds 1-3 also showed weak inhibitory activities against some tested human tumor cell lines with IC50 values in the range of 32.1-7.6 µM.

The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats.

This study explored whether valproic acid (VPA, a histone deacetylase inhibitor) could radiosensitize osteosarcoma and primary-culture tumor cells, and determined the mechanism of VPA-induced radiosensitization. The working system included osteosarcoma cells (U2OS) and primary-culture cells from chemical carcinogen (DMBA)-induced breast cancer in rats; and clonogenic survival, immunofluorescence, fluorescent in situ hybridization (FISH) for chromosome aberrations, and comet assays were used in this study. It was found that VPA at the safe or critical safe concentration of 0.5 or 1.0 mM VPA could result in the accumulation of more ionizing radiation (IR)-induced DNA double strand breaks, and increase the cell radiosensitivity. VPA-induced radiosensitivity was associated with the inhibition of DNA repair activity in the working systems. In addition, the chromosome aberrations including chromosome breaks, chromatid breaks, and radial structures significantly increased after the combination treatment of VPA and IR. Importantly, the results obtained by primary-culture cells from the tissue of chemical carcinogen-induced breast cancer in rats further confirmed our findings. The data in this study demonstrated that VPA at a safe dose was a radiosensitizer for osteosarcoma and primary-culture tumor cells through suppressing DNA-double strand breaks repair function.

[Purification and characterization of endoglucanase Egn21 from Fusarium sp. Q7-31T].

Objective: The objective of this research was to study plant cell wall degradation enzymes from Fusarium sp. Q7-31T. Methods: Strain was cultured in liquid medium with 1% (W/V) peptone as nitrogen source, 0.5% (W/V) oat straw as carbon source, 120 r/min shaking at 20 °C for 3 days. The endoglucanase Egn21 was purified by using Sephacry S-100 chromatography and DEAE-sepharose ion-exchange column chromatography. Then the enzymatic properties and MADIL-TOF-TOF identification were analyzed. Results: The molecular weight and isoelectric point (pI) of Egn21 was 44.25 kDa and 4.91, respectively. Egn21 had optimal activity with carboxymethyl cellulose at 40 °C and pH 6.0, stable at 45 °C and pH between 5.0 and 8.0, inhibited by Fe2+, Ca2+, K+, Na+, Mn2+ and inactivated by Hg2+, whereas Co2+, Zn2+ and Mg2+ had no effect. Conclusion: The enzymatic properties and MADIL-TOF-TOF results suggested that Egn21 belongs to GH5 family.

Allopurinol treatment improves renal function in patients with type 2 diabetes and asymptomatic hyperuricemia: 3-year randomized parallel-controlled study.

OBJECTIVE: To investigate the effects of long-term effective control of serum uric acid on renal function in patients with type 2 diabetes and asymptomatic hyperuricemia. METHODS: Application of randomized open parallel-controlled methods, a total of 176 patients with type 2 diabetes and asymptomatic hyperuricemia were selected, and was randomly divided into two groups for allopurinol or conventional treatments, respectively. Changes in urinary albumin excretion rate (UAER), the levels of serum creatinine and glomerular filtration rate (GFR) and the incidence of new-onset diabetic nephropathy (DN) and hypertension in patients before and after 3 years of treatment were measured and compared between groups. RESULTS: There were no statistically significant difference in the baseline clinical characteristics of study participants between two treatment groups (P > 0·05 for all). After 3 years of treatment, compared to the conventional treatment, the allopurinol treatment was more effective in reducing serum uric acid, UAER, serum creatinine (P < 0·01 for all) and increasing GFR (P < 0·01). The intention-to-treat (ITT) analysis indicated that the incidence of new-onset DN and hypertension in the allopurinol group showed a declining trend compared to that in the conventional treatment group, despite a lack of significant difference (P > 0·05). CONCLUSION: Long-term effective control of serum uric acid can decrease UAER and serum creatinine, increase GFR and may exert kidney protection effects in patients with type 2 diabetes and asymptomatic hyperuricemia.

Neuroprotective Effect of Calpeptin on Acrylamide-Induced Neuropathy in Rats.

Acrylamide (ACR) is a vinyl monomer with established human neurotoxic effects, which is characterized by the accumulation of neurofilaments (NFs) in the distal swellings of large axons in peripheral and central nervous systems. However, the mechanisms of neurotoxicity remain unclear. The objective is to investigate the neuroprotective effect of calpeptin (CP) on ACR-induced neuropathy and its mechanism. Female adult Wistar rats were randomly divided into four groups (control, CP, ACR, and ACR + CP group). Control group received 0.9 % saline, ACR and ACR + CP groups received 30 mg/kg ACR by intraperitoneal injection. In addition, CP and ACR + CP groups also received 200 µg/kg CP. Gait analysis and hind limb splay were measured weekly to analyze neurobehavioral changes. The calpain activity and the changes of NFs protein levels in spinal cord are determined. Compared with control group, body weight of rats in ACR group decreased by 11.3 % (P < 0.01), while in ACR + CP group body weight increased significantly by 8.3 % (P < 0.01) compared with ACR group by the end of the 4th week; gait score of rats in both ACR and ACR + CP groups increased significantly by 167 % and 100 % (P < 0.01) compared with control group, while it decreased significantly by 25.1 % (P < 0.01) in ACR + CP group compared with ACR group; the distance of hind limb splay in both ACR and ACR + CP groups increased by 76.7 % and 49.5 % (P < 0.01) compared with control group, while it decreased by 15.4 % (P < 0.01) in ACR + CP group compared with ACR group; calpain activity of spinal cord at ACR and ACR + CP groups increased significantly by 14.9 % and 10.0 % (P < 0.01) compared with control group, while it decreased 4.2 % (P < 0.01) in ACR + CP group compared with ACR group; compared with control group, the levels of light NF (NF-L), medium NF (NF-M) and heavy NF (NF-H) subunits increased by 81.2 %, 263.6 % and 22.6 % (P < 0.01) in the supernatant of ACR group in spinal cord tissue and increased by 28.4 %, 96.6 % and 10.6 % (P < 0.01) in ACR + CP group, while the levels of NF-L, NF-M and NF-H subunits decreased by 29.1 %, 45.9 % and 9.8 % (P < 0.01) in ACR + CP group compared with ACR group. The present results suggested that CP can relieve ACR neuropathy by decrease calpain activity and NFs degradation. The changes of calpain activity and NFs may be one of the mechanisms of ACR-induced neuropathy.

Synthesis of functional xLayMn/KIT-6 and features in hot coal gas desulphurization.

To enhance the stability of sorbents during continuous desulphurization-regeneration cycles, KIT-6 with 3D pore channels was used as a support for the sorbents. A series of mesoporous xLayMn/KIT-6 sorbents with different La/Mn atomic ratios were fabricated using a sol-gel method and their desulphurization properties of hot coal gas were investigated at 700-850 °C. 3La97Mn/KIT-6 performed the best at 800 °C with a breakthrough sulphur capacity of 11.56 g sulphur per 100 g sorbent. The eight successive desulphurization (800 °C)-regeneration (600 °C) cycles revealed that 3La97Mn/KIT-6 with endurable regeneration abilities could retain 80% of the initial sulphur capacity. It indicated a better desulphurization performance compared to pure 3La97Mn and 3La97Mn/MCM-41. The fresh and used xLayMn/KIT-6 sorbents were characterized by means of BET, XRD, HRTEM, XPS and H2-TPR techniques. The XRD patterns and HRTEM images of fresh and used 3La97Mn/KIT-6 verified that the utilization of KIT-6 effectively suppressed the aggregation of Mn2O3 particles and improved the stability of the sorbent.

Prognostic role of hormone receptors in endometrial cancer: a systematic review and meta-analysis.

BACKGROUND: The aim of this study was to summarize the global predicting role of hormone receptors for survival in endometrial cancer. METHODS: Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall survival (OS), cancer-specific survival (CSS), or progression-free survival (PFS) in patients with elevated levels of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2) with those in patients with lower levels. The combined hazard ratios of ER, PR, and HER2 for survival were calculated. RESULTS: A total of 98 studies were included for meta-analysis (44 for ER, 38 for PR, and 16 for HER2). Higher levels of either ER or PR could significantly indicate better survival. The pooled hazard ratios (HRs) of ER for OS, CSS, and PFS were 0.75 (95% CI, 0.68-0.83), 0.45 (95% CI, 0.33-0.62), and 0.66 (95% CI, 0.52-0.85), respectively. The combined HRs of PR for OS, CSS, and PFS reached 0.63 (95% CI, 0.56-0.71), 0.62 (95% CI, 0.42-0.93), and 0.45 (95% CI, 0.30-0.68), respectively. In contrast, elevated levels of HER2 could predict worse outcome with a HR of 1.98 (95% CI, 1.49-2.62) for OS, and a HR of 2.26 (95% CI, 1.57-3.25) for PFS. CONCLUSIONS: In patients with endometrial cancer, higher level of ER and PR predicted favorable survival, and increased level of HER2 was associated with poorer survival. All of the three hormone receptors had prognostic value for survival.

Effects of dietary L-glutamine supplementation on specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine.

Little is known about effects of dietary glutamine supplementation on specific and general defense responses in a vaccine-immunized animal model. Thus, this study determined roles for dietary glutamine supplementation in specific and general defense responses in mice immunized with inactivated Pasteurella multocida vaccine. The measured variables included: (1) the production of pathogen-specific antibodies; (2) mRNA levels for pro-inflammatory cytokines, toll-like receptors and anti-oxidative factors; and (3) the distribution of P. multocida in tissues and the expression of its major virulence factors in vivo. Dietary supplementation with 0.5 % glutamine had a better protective role than 1 or 2 % glutamine against P. multocida infection in vaccine-immunized mice, at least partly resulting from its effects in modulation of general defense responses. Dietary glutamine supplementation had little effects on the production of P. multocida-specific antibodies. Compared to the non-supplemented group, dietary supplementation with 0.5 % glutamine had no effect on bacterial burden in vivo but decreased the expression of major virulence factors in the spleen. Collectively, supplementing 0.5 % glutamine to a conventional diet provides benefits in vaccine-immunized mice by enhancing general defense responses and decreasing expression of specific virulence factors.