Functionalized lignin nanoparticles assembled with MXene reinforced polypropylene with favorable UV-aging resistance, electromagnetic shielding effects and superior fire-safety.

Deterioration in mechanical performances and aging resistance due to the introduction of flame retardants is a major obstacle for bio-based fire-safety polypropylene (PP). Herein, we reported a kind of functionalized lignin nanoparticles assembled with MXene (MX@LNP), and applied it to construct the flame-retardant PP composites (PP-MA) with superior fire safety, excellent mechanical performance, electromagnetic shielding effects and aging resistance. Specifically, the PP-MA doped with only 18 wt% flame-retardant additives (PP-MA18) achieved the UL-94 V-0 rating. In comparison to pure PP, PP-MA18 presented a greatly decreased peak of heat release rate (pHRR), total heat rate (THR), and peak smoke production rate (pSPR) by 79.7 %, 69.0 % and 75.8 %, respectively, and satisfactory decrease in total flammable and toxic volatiles evolved. The formed fine solid microstructure of carbon residuals effectively promoted the compactness of char layers. More importantly, the nano-effect and the strong interface interaction between the complexed MX@LNP and PP enhanced the tensile strength (45.78 MPa) and elongation at break (725.95 %) of PP-MA. Additionally, the significant ultraviolet absorption and electromagnetic wave dissipation performance of MXene and lignin enabled excellent aging resistance and electromagnetic shielding effects of PP-MA compared with PP. This achieved MX@LNP afforded a novel approach for developing flame retardant materials with excellent application performance.

Hepatocytic lipocalin-2 controls HDL metabolism and atherosclerosis via Nedd4-1-SR-BI axis in mice.

High-density lipoprotein (HDL) metabolism is regulated by complex interplay between the scavenger receptor group B type 1 (SR-BI) and multiple signaling molecules in the liver. Here, we show that lipocalin-2 (Lcn2) is a key regulator of hepatic SR-BI, HDL metabolism, and atherosclerosis. Overexpression of human Lcn2 in hepatocytes attenuates the development of atherosclerosis via SR-BI in western-diet-fed Ldlr-/- mice, whereas hepatocyte-specific ablation of Lcn2 has the opposite effect. Mechanistically, hepatocyte Lcn2 improves HDL metabolism and alleviates atherogenesis by blocking Nedd4-1-mediated SR-BI ubiquitination at K500 and K508. The Lcn2-improved HDL metabolism is abolished in mice with hepatocyte-specific Nedd4-1 or SR-BI deletion and in SR-BI (K500A/K508A) mutation mice. This study identifies a regulatory axis from Lcn2 to HDL via blocking Nedd4-1-mediated SR-BI ubiquitination and demonstrates that hepatocyte Lcn2 may be a promising target to improve HDL metabolism to treat atherosclerotic cardiovascular diseases.

The expression and clinical value of LRP11, FUBP1 and TET1 in cervical cancer.

Cervical cancer is the second leading cause of cancer death among women worldwide. Identification of effective genes along with biological markers as targeting agents is very necessary for the diagnosis and treatment of this disease. Bioinformatics techniques along with genetic and molecular investigations have provided the possibility of studying different levels of information such as the genome, transcriptome, proteome, and metabolize with high depth and accuracy. The collection of these data provides comprehensive and valuable information about the investigated phenotypes, including complex diseases such as cancer. In this study, we examined three genes LRP11, FUBP1, and TET1 related to cervical cancer. The results of this study showed that the level of expression of these genes is high in lymph nodes and the thyroid and is less in the pancreas and liver. Also, the expression level of the FUBP1 gene is higher than that of LRP11, and the expression level of the LRP11 gene is higher than that of TET1. Regarding the structure and proteomics of the studied genes, it can be seen that due to the presence of more domains in the LRP11 and FUBP1 genes, these genes probably independently participate in various functions and have a wider range of activity than the TET1 gene. Also, the analysis of the stability of the examined genes showed that the stability of the FUBP1 gene is relatively higher than that of the TET1 gene, and this gene is also more stable than the LRP11 gene. Considering that these genes are effective key genes for the early detection of cervical cancer, it is hoped that they will be used as markers in the diagnosis and treatment of cervical cancer.

Activating transcription factor 3, glucolipid metabolism, and metabolic diseases.

Lipids and glucose exert many essential physiological functions, such as providing raw materials or energy for cellular biosynthesis, regulating cell signal transduction, and maintaining a constant body temperature. Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases. Activating transcription factor 3 (ATF3) is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation, apoptosis, DNA repair, and oncogenesis. Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism. ATF3 inhibits intestinal lipid absorption, enhances hepatic triglyceride hydrolysis and fatty acid oxidation, promotes macrophage reverse cholesterol transport, and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis. In addition to its role in lipid metabolism, ATF3 has also been identified as an important regulator of glucose metabolism. Here, we summarize the recent advances in the understanding of ATF3, mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.

Application of the clearance rate of inflammatory markers for evaluation of the therapeutic effect in adult bacterial bloodstream infection.

BACKGROUND: Bloodstream infection (BSI) is a serious systemic infectious disease. This study aimed to investigate the application of the clearance rate of interleukin-6, procalcitonin, and C-reactive protein for the evaluation of antimicrobial efficacy in adult bacterial BSI without other inflammatory factors. METHODS: Patients with positive blood culture and without other inflammatory factors in The First Hospital of Hebei Medical University from January 2017 to December 2019, who received continuous detection interleukin-6, procalcitonin, and C-reactive protein, were selected. The clearance rate of these inflammatory markers was calculated, and the consistency test (kappa test) was performed to analyze the clinical outcomes (cure, improvement, delay, deterioration, or death). RESULTS: For adult patients with bacterial BSI without other inflammatory factors, the testing speculation based on the clearance rate of interleukin-6 and C-reactive protein was consistent with the clinical outcome of the patients, with kappa values of 0.784 and 0.714, respectively (P=0.000). The testing speculation based on the procalcitonin clearance rate was generally consistent with the clinical outcome, with a kappa value of 0.685 (P=0.000). The testing speculation based on the procalcitonin clearance rate showed good consistency with the clinical outcome of patients with Gram-positive cocci infection, kappa =0.813 (P=0.000); for patients with gram-negative bacilli infection, the consistency of clinical outcomes was general, kappa =0.649 (P=0.000). CONCLUSIONS: In adult patients with bacterial BSI without other inflammatory factors, the clearance rate of interleukin-6, procalcitonin, and C-reactive protein can predict the clinical outcome within 24 hours, among which the procalcitonin clearance rate can better predict the clinical outcome of patients with Gram-negative bacilli infection. This approach can be used to evaluate the effectiveness of anti-infection treatment in early-stage BSI.

Screening target genes for the treatment of PCOS via analysis of single-cell sequencing data.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a condition of the female reproductive system and it remains imperative to identify target genes responsible for its pathogenesis and develop therapeutic drugs capable of effectively treating it. METHODS: We performed primary screening, staging, functional analysis as well as screening of target genes and therapeutic drugs based on single cell sequencing data of 34 oocytes from the GEO database. RESULTS: Oxidative phosphorylation played a pivotal role in the development of oocytes, insulin resistance and ovulation disorders. At the cellular level, GV and MI phases were particularly critical for the biology of pregnancy. We screened PGR, SIRT1 and ADAMTS1 as hub differentially expressed genes (DEGs) and found relevant drugs using the Drug-Gene Interaction Database. In clinical study, oral contraceptives and insulin sensitisers were found to be effective in the treatment of PCOS. CONCLUSION: PGR, SIRT1 and ADAMTS1 were found to be down-regulated in oocytes, ovulation and female pregnancy. These 3 genes are likely biomarkers important in the treatment of PCOS. Insulin sensitiser in combination with oral contraceptive administration were found to significantly improve PCOS.Key messagesOur study used a new bioinformatics approach to find target genes for the treatment of PCOS.Our study sought to identify target genes that affect human oocyte quality by analysing single-cell sequencing data from oocytes.We testified to our data by analysing a subset of clinical data.

Clinical Value of Cytokine Assay in Diagnosis and Severity Assessment of Lung Cancer.

Purpose: To investigate the clinical value of interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) in diagnosis and severity assessment of lung cancer. Methods: In this observational study, 50 physical examination healthy subjects were included in the control group and 100 lung cancer patients were included in the study group. In the study group, 53 cases with pleural effusion were subgrouped to the pleural effusion group (n = 53), while 47 patients were assigned to the nonpleural effusion group (n = 47). Plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of all eligible subjects were collected and compared. Results: The study group showed significantly higher levels of plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ versus healthy subjects (P < 0.05). Deterioration of lung cancer was associated with increased plasma cytokine levels and APACHE II scores. The combination assay of the above plasma cytokines showed significantly better diagnostic efficacy for lung cancer versus the single assay of the cytokines. Dead patients had higher plasma cytokine levels versus survived patients. The accuracy of plasma IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ levels in the severity assessment of lung cancer was comparable with that of the APACHE II scale. Conclusion: The plasma cytokines IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ are effective markers for the diagnosis of lung cancer. The combined assay contributes to the early diagnosis of lung cancer patients, and the persistent elevation of cytokines suggests an increased risk of death in lung cancer patients, so the detection of cytokine levels facilitates the severity assessment of lung cancer.

Lysine-specific demethylase 1 aggravated oxidative stress and ferroptosis induced by renal ischemia and reperfusion injury through activation of TLR4/NOX4 pathway in mice.

Acute kidney injury (AKI) is mainly caused by renal ischaemia reperfusion injury (IRI). Lots of evidence suggests that ferroptosis and oxidative stress play the vital role in renal IRI. However, the specific mechanism of renal IRI has not been fully elucidated. lysine-specific demethylase 1 (LSD1) has been shown to regulate the pathogenesis of kidney disease. In this study, we firstly found that LSD1 was positively related to renal IRI. TCP, a classical LSD1 inhibitor, could alleviate tissue damage induced by renal IRI. Inhibition of LSD1 with either TCP or LSD1 knockdown could alleviate ferroptosis and oxidative stress caused by IRI both in vivo and in vitro. Furthermore, the results showed that suppression of LSD1 decreased the expression of TLR4/NOX4 pathway in HK-2 cells subjected to H/R. With the si-RNA against TLR4 or NOX4, it showed that the silence of TLR4/NOX4 reduced oxidative stress and ferroptosis in vitro. Moreover, to demonstrate the crucial role of TLR4/NOX4, TLR4 reduction, mediated by inhibition of LSD1, was compensated through delivering the adenovirus carrying TLR4 in vitro. The results showed that the compensation of TLR4 blunted the alleviation of oxidative stress and ferroptosis, induced by LSD1 inhibition. Further study showed that LSD1 activates TLR4/NOX4 pathway by reducing the enrichment of H3K9me2 in the TLR4 promoter region. In conclusion, our results demonstrated that LSD1 inhibition blocked ferroptosis and oxidative stress caused by renal IRI through the TLR4/NOX4 pathway, indicating that LSD1 could be a potential therapeutic target for renal IRI.

Overexpression of MFN2 alleviates sorafenib-induced cardiomyocyte necroptosis via the MAM-CaMKIIδ pathway in vitro and in vivo.

Background: The continued success of oncological therapeutics is dependent on the mitigation of treatment-related adverse events, particularly cardiovascular toxicities. As such, there is an important need to understand the basic mechanisms of drug toxicities in the process of antitumor therapy. Our aim in this study was to elucidate the underlying mechanisms of sorafenib (sor)-induced cardiomyocyte damage. Methods: Primary mouse cardiomyocytes were prepared and treated with sor and various other treatments. Cardiomyocyte necroptosis was detected by flow cytometry, western blotting, and CCK8 assays. Mitochondrial Ca2+ uptake was detected by the Rhod-2 probe using confocal imaging. Morphological changes in mitochondria and mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) were imaged using transmission electron microscopy (TEM) and confocal microscopy. Cardiac perfusion was performed to detect cardiac specific role of MFN2 overexpression in vivo. Results: We reported that mitochondrial Ca2+ overload, the subsequent increase in calmodulin-dependent protein kinase II delta (CaMKIIδ) and RIP3/MLKL cascade activation, contributed to sor-induced cardiac necroptosis. Excess MAM formation and close ER-mitochondria contact were key pathogenesis of sor-induced Ca2+ overload. Sor mediated MFN2 downregulation in a concentration-dependent manner. Furthermore, we found that reduced mitofusin-2 (MFN2) level augmented sor-mediated elevated MAM biogenesis and increased mitochondria-MAM tethering in cardiomyocytes. Sor-induced Mammalian Target of Rapamycin (mTOR) inactivation, followed by the activation and nuclear translocation of Transcription Factor EB (TFEB), contributed to mitophagy and MFN2 degradation. In an in vivo model, mice subjected to sor administration developed cardiac dysfunction, autophagy activation and necroptosis; our investigation found that global and cardiac-specific overexpression of MFN2 repressed cardiac dysfunction, and sor-induced cardiomyocyte necroptosis via repressing the MAM-CaMKIIδ-RIP3/MLKL pathway. Conclusion: Sorafenib mediated cardiomyocyte necroptosis through the MFN2-MAM-Ca2+-CaMKIIδ pathway in vitro and in vivo. The overexpression of MFN2 could rescue sor-induced cardiomyocyte necroptosis without disturbing the anti-tumor effects.

Thrombopoietic effects of CCAAT/enhancer-binding protein ß on the early-stage differentiation of megakaryocytes.

CCAAT/enhancer-binding protein ß (C/EBPß) is a transcription factor that is involved in adipocytic and monocytic differentiation. However, the physiological role of C/EBPß in megakaryocytes (MKs) is not clear. In this study, we investigated the effects of C/EBPß on the early-stage differentiation of MKs, and explored the potential mechanisms of action. We established a cytosine arabinoside-induced thrombocytopenia mouse model using C57BL/6 mice. In the thrombocytopenia mice, the platelet count was found to be decreased, and the mRNA and protein expression levels of C/EBPß in MKs were also reduced. Furthermore, the maturation of Dami (MKs cell line) cells was induced by phorbol 12-myristate 13-acetate. When C/EBPß was silenced in Dami cells by transfection using C/EBPß-small interfering RNA, the expression of MKs-specific markers CD41 and CD62P, was dramatically decreased, resulting in morphological changes and differentiation retardation in low ploidy, which were evaluated using flow cytometry, real-time polymerase chain reaction, western blot, and confocal microscopy. The mitogen activated protein kinase-extracellular signal-regulated kinase signaling pathway was found to be required for the differentiation of MKs; knockdown of C/EBPß in MEK/ERK1/2 pathway attenuated MKs differentiation. Overexpression of C/EBPß in MEK/ERK1/2 pathway inhibited by U0126 did not promote MKs differentiation. To the best of our knowledge, C/EBPß plays an important role in MKs differentiation and polyploidy cell cycle control. Taken together, C/EBPß may have thrombopoietic effects in the differentiation of MKs, and may assist in the development of treatments for various disorders.

Estrogen promotes lncRNA H19 expression to regulate osteogenic differentiation of BMSCs and reduce osteoporosis via miR-532-3p/SIRT1 axis.

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) plays an essential role in bone formation. Its imbalance can lead to osteoporosis. Estrogen and long noncoding RNAs (lncRNAs) have been confirmed to participate in osteogenesis. However, the underlying mechanism remains unclear. The purpose of our study was to explore the function of lncRNA H19 in estrogen-induced osteogenic differentiation of BMSCs. The present research demonstrated that the expression levels of lncRNA H19 and SIRT1 were markedly downregulated in postmenopausal osteoporosis (PMOP), while miR-532-3p expression was obviously increased. Moreover, estrogen induced the osteogenic differentiation of BMSCs by upregulating lncRNA H19. Furthermore, our integrated experiments showed that lncRNA H19 caused a decrease in the expression of miR-532-3p, which was verified to target SIRT1 directly. Additionally, estrogen alleviated osteoporosis in OVX rats through lncRNA H19-mediated miR-532-3p/SIRT1 axis. Our findings imply that lncRNA H19 mediates estrogen-regulated osteogenic differentiation in BMSCs via miR-532-3p/SIRT1 signalling and may become a novel target for alleviating PMOP.

Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice.

High-density lipoprotein (HDL), a well-known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL-targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient (SR-BI-/- ) mice. First, we demonstrated that MsrA overexpression attenuated ROS level and inflammation in HepG2 cells. For the in vivo study, SR-BI-/- mice were intravenously injected with lentivirus to achieve hepatic MsrA overexpression. High-level hepatic MsrA significantly reduced the plasma free cholesterol contents, improved HDL functional proteins apolipoprotein A-I (apoAI), apoE, paraoxonase1 (PON1), and lecithin:cholesterol acyltransferase (LCAT), while decreased the pro-inflammatory property of dysfunctional HDL, contributing to reduced atherosclerosis and hepatic steatosis in Western diet-fed mice. Furthermore, the study revealed that hepatic MsrA altered the expression of several genes controlling HDL biogenesis, cholesterol esterification, cholesterol uptake mediated by low-density lipoprotein receptor (LDLR) and biliary excretion, as well as suppressed nuclear factor κB (NF-κB) signaling pathway, which largely relied on liver X receptor alpha (LXRα)-upregulation. These results provide original evidence that MsrA may be a promising target for the therapy of dysfunctional HDL-related CVD.

Layered double hydroxide nanosheets: towards ultrasensitive tumor microenvironment responsive synergistic therapy.

The tumor microenvironment (TME), which is characterised by high H2O2 and glutathione (GSH) levels, low pH value and hypoxia, imposes crucial influences on tumor therapeutic outcomes. Rational design and preparation of nanomaterial systems that are responsive to the intrinsic properties of the TME open a promising avenue towards tumor-specific treatment. Herein, CoMn-layered double hydroxide (CoMn-LDH) nanosheets were synthesized via a bottom-up method followed by surface modification with a photosensitizer, chlorin e6 (Ce6), which exhibited TME-responsive imaging as well as photodynamic and chemodynamic synergistic therapy (PDT/CDT). Due to their ultralow bond energy and large adsorption energy, CoMn-LDH nanosheets show fast self-degradability in a GSH (10 mM) microenvironment, giving an excellent CDT activity in mildly acidic conditions (pH = 6.5), superior GSH removal ability (99.82%) and O2 production (35.37 µg L-1 s-1). Moreover, Ce6/CoMn-LDH nanosheets display satisfactory photoacoustic (PA) imaging and GSH-enhanced magnetic resonance imaging (MRI) with a 45.1-fold T1-enhancement. In addition, both in vitro and in vivo therapeutic tests based on Ce6/CoMn-LDH demonstrate a satisfactory anticancer activity with complete cancer cell apoptosis and dramatic tumor elimination. This work provides a new perspective for the design of multifunctional 2D nanosheets towards a fully promoted TME-responsive synergistic therapy, which holds great promise for future clinical diagnosis and treatment.

Risk factors for venous thromboembolism in individuals undergoing coronary artery bypass grafting.

OBJECTIVE: Venous thromboembolism (VTE) can easily occur after coronary artery bypass grafting (CABG). We assessed the proportion of patients with a diagnosis of VTE after CABG and determined the associated risk factors and complications in these patients. METHODS: We assessed all the patients included in the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2015 who had undergone CABG. The demographic characteristics, surgical parameters, and complications were analyzed using single-factor and binary logistic regression analyses to identify the risk factors for VTE after CABG. RESULTS: Overall, 8956 patients were identified. Postoperative VTE was found in 1.75% of these patients, with pulmonary embolism and deep vein thrombosis accounting for 0.61% and 1.28%, respectively; 0.15% of the patients had both conditions. The patients who had developed VTE had greater odds of being white and having an American Society of Anesthesiologists classification of ≥5. Multivariate analysis showed that a history of bleeding disorders, congestive heart failure, and operative time of ≥310 minutes were risk factors for the development of postoperative VTE. Patients with VTE had worse outcomes, including greater odds of returning to the operating room, hospitalization, unplanned reoperation, and readmission. The occurrence of VTE was associated with several postoperative complications, including emergency intubation, ventilator time >48 hours, pneumonia, urinary tract infection, peri- and postoperative transfusions, gradual kidney function reduction, acute kidney failure, cardiac arrest necessitating cardiopulmonary resuscitation, myocardial infarction, and septic shock. CONCLUSIONS: The overall VTE rate after CABG has been low. However, the condition has been associated with worse 30-day postoperative outcomes and complications. The independent predictors of VTE development included a history of bleeding disorders, congestive heart failure in the 30 days before surgery, and operative time of ≥310 minutes. Understanding these risk factors should aid physicians in the decisions regarding prophylaxis and treatment.

The Immunomodulatory Activity of Polysaccharides from the Medicinal Mushroom Amauroderma rude (Agaricomycetes) Is Mediated via the iNOS and PLA2-AA Pathways.

Our earlier work indicated that the polysaccharides of Amauroderma rude (AR) appear to have an effect on immunoregulation. However, the pathways are not clear. In this paper, we discuss the immunomodulatory mechanisms of A. rude to provide a scientific basis for its possible use as a food. Amauroderma rude increased the expression of iNOS and P38 in the Raw246.7 cell line. When the AR concentration reached 150 µg/mL, the expressions of iNOS and P38 increased 23.0% and 191.7%, respectively. When the AR concentrations were 50 µg/mL, the concentrations of cytokines IL-2, TNF-α, and IFN-γ were 33.65 pg/mL, 12.53 pg/mL and 42.56 pg/mL. When AR reached 200 µg/mL, the lgA and lgM levels were 0.73 µg/mL and 1.5 µg/mL. When AR reached 400 µg/mL, the lgG level reached 1.65 µg/mL by ELISA assay. When 4.8 mg AR were orally administered, IL-2, TNF-α, IFN-γ, PGE2, and LTB4 increased dramatically, to 0.17 pg/mL, 0.16 pg/mL, 0.15 pg/mL, 30.71 pg/mL, and 18.68 pg/mL, respectively. The concentrations of lgA, lgM, and lgG, AA, and PLA2 also increased significantly to 2.62 pg/mL, 2.14 pg/mL, 2.06 pg/mL, 5.23 µg/mL and 3.68 ng/mL, respectively. With 4.8 mg AR p.o., iNOS protein expression increased 16.8% and P38 increased 234.0%. These results indicate that A. rude polysaccharides stimulate cytokine production and activate the iNOS, PLA2-AA, and MAPK pathways during the immunomodulatory process.

Establishment and evaluation of a novel mouse model of peri/postmenopausal depression.

Women are believed to be more vulnerable to develop depressive symptoms during the perimenopause compared to postmenopause. The traditional bilateral ovariectomy and chronic mild stress (CMS) stimulation animal model produces a postmenopausal depressive-like state but the transition from perimenopausal period to postmenopausal period was ignored. Thus we establish a novel animal model in which the mice were stimulated by CMS for three months and removed the ovaries by two-step operation, and then evaluate whether this novel model could be much better for preclinical study used as a peri/postmenopause depressive model. The present study systemically evaluated the changes induced by two-step ovariectomy plus CMS in the mice. The depression-like behaviors, the levels of corticosterone, estrogen, pro-inflammatory factors, neurotransmitters, as well as brain-derived neurotrophic factor were determined; the changes of estrogen receptors, serotonin receptors, uterine weight and bone microarchitecture were also observed. The results show that the behaviors and biochemical indexes of mice changed gradually over time. Our study suggests that this two-step ovariectomy operation plus CMS successfully establishes a more reasonable peri/postmenopausal depression animal model which effectively simulates the clinical symptoms of peri/postmenopausal depressive women.

Activation of the AKT/FOXO3a Signaling Pathway during Breast Cancer Inhibition In Vivo and In Vitro by Amauroderma rude (Agaricomycetes).

We previously reported that Amauroderma rude polysaccharides (AR) displayed strong immunomodulatory tumor-suppressive effects in mice. The current study was designed to explore the potential mechanism by which AR polysaccharides inhibit tumor growth. We found that AR could effectively induce cell death in 4T1 and MDA-MB-231 breast cancer cells. AR could also inhibit tumor cell migration and invasion, significantly promote apoptosis in 4T1 cells, and significantly increase CDK4, CDK6, cylinD1, and P27 mRNA expression in mice. Additionally, AR was able to significantly increase FOXO3a expression and decrease p-AKT expression both in vitro and in vivo, indicating that the AKT/FOXO3a signaling pathway had been activated during the inhibitory process.

Acute and Subchronic Toxicity of Dusky-Skinned Mushroom, Amauroderma rude (Agaricomycetes).

Our earlier work indicated that Amauroderma rude seems to have an effect on immunoregulation and tumor inhibition. However, its toxicity is not yet clear. The aim of this work is to demonstrate the acute and subchronic toxicity of A. rude in order to provide a scientific basis for its possible use as a food. The acute toxicity study (involving mice) showed that the median lethal dose of the A. rude extract was >15,000 mg/kg. In the repeated-dose 90-day oral toxicity study (involving rats), the administration of A. rude extract at 0.1 (AR0.1), 0.2 (AR0.2), and 0.4 g (AR0.4) per rat produced no significant difference in food or water consumption or changes in body weight, hematological parameters, biochemical parameters, relative organ weights, organ coefficients, or histopathology compared with the control group. Analyses of these results with data from monitoring the appearance, behavior, and health of the animals indicate that the oral administration of A. rude extract daily for 90 days does not cause subchronic toxicity.

Synergistic effects of baicalein with gemcitabine or docetaxel on the proliferation, migration and apoptosis of pancreatic cancer cells.

Baicalein, a type of flavonoids extracted from Scutellaria baicalensis Georgi, has been reported to be a very promising drug for pancreatic cancer. However, it is unclear whether combination of baicalein with gemcitabine or docetaxel is synergistic to the treatment for pancreatic cancer (PC). We investigated the combinational effects of baicalein with gemcitabine or docetaxel on proliferation, cell cycle, migration and apoptosis of human PC cells. Administration of baicalein alone significantly inhibit the proliferation of PC cells. Notably, when it is combined with gemcitabine or docetaxel, combination index (CI) values calculated by Calcusyn software are smaller than 1, indicating the synergism of baicalein with gemcitabine or docetaxel for the treatment of PC cells. Consistently, EdU assay showed that administration of baicalein significantly enhanced the capacity of gemicitabine to inhibit proliferation of PC cells. Cell cycle analysis showed that high-concentration of baicalein was able to arrest PC cells in the S phase. Furthermore, low concentration of baicalein in combination with either gemcitabine or docetaxel exhibited strong suppression on the migration of PC cells. A further study using transmission electron microscope (TEM), DAPI staining and western blot showed that baicalein induced-apoptosis of PC cells might be via caspase-3/PARP signaling pathway. Notably, combination treatment was able to induce more severe cell apoptosis of PC cells. In conclusion, baicalein exhibited synergistic effects with gemcitabine or docetaxel on the treatment of PC cells.

Fine physical and genetic mapping of powdery mildew resistance gene MlIW172 originating from wild emmer (Triticum dicoccoides).

Powdery mildew, caused by Blumeria graminis f. sp. tritici, is one of the most important wheat diseases in the world. In this study, a single dominant powdery mildew resistance gene MlIW172 was identified in the IW172 wild emmer accession and mapped to the distal region of chromosome arm 7AL (bin7AL-16-0.86-0.90) via molecular marker analysis. MlIW172 was closely linked with the RFLP probe Xpsr680-derived STS marker Xmag2185 and the EST markers BE405531 and BE637476. This suggested that MlIW172 might be allelic to the Pm1 locus or a new locus closely linked to Pm1. By screening genomic BAC library of durum wheat cv. Langdon and 7AL-specific BAC library of hexaploid wheat cv. Chinese Spring, and after analyzing genome scaffolds of Triticum urartu containing the marker sequences, additional markers were developed to construct a fine genetic linkage map on the MlIW172 locus region and to delineate the resistance gene within a 0.48 cM interval. Comparative genetics analyses using ESTs and RFLP probe sequences flanking the MlIW172 region against other grass species revealed a general co-linearity in this region with the orthologous genomic regions of rice chromosome 6, Brachypodium chromosome 1, and sorghum chromosome 10. However, orthologous resistance gene-like RGA sequences were only present in wheat and Brachypodium. The BAC contigs and sequence scaffolds that we have developed provide a framework for the physical mapping and map-based cloning of MlIW172.