CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.

The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.

The Effect of Perioperative Comprehensive Nursing on Patients Undergoing Ovary Endometriosis Laparoscopic Surgery.

Objective: To assess the effectiveness of perioperative nursing interventions in improving outcomes and satisfaction for patients undergoing laparoscopic surgery for ovarian endometriosis. Methods: From July 2021 to September 2022, 80 patients with endometriosis underwent laparoscopic surgery at Shijiazhuang Fourth Hospital and were randomly assigned to the conventional (n=40) and experimental (n=40) groups. During the perioperative period, patients in the conventional group received standard nursing interventions, while patients in the experimental group received comprehensive nursing interventions. The two groups were compared in terms of postoperative clinical indicators, self-rated anxiety scale (SAS) and self-rated depression scale (SDS) scores, nursing compliance, complications, and nursing satisfaction. Results: comprehensive nursing resulted in better postoperative clinical indices (time to get out of bed, hospital stay) versus routine nursing (all P < .001). The comprehensive nursing led to significantly lower SAS and SDS scores versus routine nursing. The nursing compliance of the patients in the experimental group was significantly higher than that of the patients in the conventional group (P < .001). Comprehensive nursing was associated with a significantly lower incidence of complications versus routine nursing (P < .001). Comprehensive nursing contributed to significantly higher nursing satisfaction versus routine nursing (P < .001). Conclusion: Comprehensive perioperative nursing interventions for patients with ovarian endometriosis undergoing laparoscopic surgery considerably accelerate patient recovery and enhance nursing compliance, as well as minimize patient negative emotions and improve patient satisfaction with nursing.  The comprehensive approach addresses the specific needs of patients during the recovery period, minimizing postoperative complications, accelerating patient recovery, and improving overall quality of life. By integrating psychological support, tailored strategies for pain management, early mobilization, and prompt intervention for complications, this intervention sets a benchmark for holistic care in gynecological surgery.

The moderating role of work environment in the relationship between proactive personality and personal growth initiative among nurses: a cross-sectional study.

BACKGROUNDS: Personal growth initiative (PGI) is regarded as a meaningful concept with potential value at both the individual and organizational levels, but little is known about the factors that contribute to nurses' PGI. This study aimed to explore how proactive personality and hospital work environment affect PGI of clinical nurses. METHODS: A cross-sectional study was conducted between September and October 2022 among 4414 nurses from 10 tertiary general hospitals in 10 cities in Sichuan, China, using a two-stage sampling method. Self-reported anonymous online questionnaires, such as sociodemographic information survey, personal growth initiative scale II, the 10-item proactive personality scale, and practice environment scale-nursing work index were used to collect data. Multiple hierarchical regression analyses were performed to examine research hypotheses. RESULTS: Among the control variables in this study, nurses' self-perceptions of general health status and professional title positively predicted PGI (ß = 0.462, 95%CI = 0.272-0.653; ß = 1.078, 95%CI = 0.508-1.648). After adding control variables, both proactive personality (ß = 1.143, 95%CI = 1.096-1.190) and work environment (ß = 3.391, 95%CI = 2.904-3.879) positively predicted PGI. The work environment positively moderated the association between proactive personality and PGI (ß = 0.108, 95%CI = 0.025-0.191). These predictors jointly explained 50.3% of the variance in PGI. CONCLUSIONS: Nurses with a greater tendency to have a typical proactive personality have higher levels of personal growth initiative, and this positive effect will be better highlighted in a healthier work environment. Nursing managers should prioritize the employment of people with proactive personality traits, focus on the development and stimulation of proactive personality traits in nurses, and establish a supportive work environment to maximize the personal growth initiative of nurses.

Response of Arctic Black Carbon Contamination and Climate Forcing to Global Supply Chain Relocation.

Black carbon (BC) plays a vital role in Arctic warming. Extensive investigations have been conducted to elucidate the source-receptor relationships of BC between the Arctic and mid-/high-latitude sources. However, it is unclear to what extent source relocation under globalization could disturb Arctic BC contamination and climate forcing from anthropogenic BC emissions. Here, we show that the global supply chain (GSC) relocation featured by the southward shift of industries from high-latitude developed countries to low-latitude developing countries markedly reduces the BC burden in the Arctic using a global chemical transport model (GEOS-Chem) and a multiregional input-output analysis (MRIO). We find that Arctic annual mean BC concentration associated with the GSC relocation drops by ∼15% from the case without the GSC relocation. The total net BC level declines 7% over the entire Arctic and 16% in the European Arctic. We also observed markedly declining BC deposition as well as direct and snow albedo radiative forcing in the Arctic. We show that the Arctic BC burden would be further reduced by decreasing BC emissions in China, attributable to its emission reduction and ongoing shift of the GSC from China to southern and southeastern Asia.

A Novel Method for the Pre-Column Derivatization of Saccharides from Polygonatum cyrtonema Hua. by Integrating Lambert-Beer Law and Response Surface Methodology.

Traditional Chinese medicine (TCM) safety and effectiveness can be ensured by establishing a suitable quality assessment system. This work aims to develop a pre-column derivatization HPLC method for Polygonatum cyrtonema Hua. quality control. In this study, 1-(4'-cyanophenyl)-3-methyl-5-pyrazolone (CPMP) was synthesized and reacted with monosaccharides derived from P. cyrtonema polysaccharides (PCPs), followed by HPLC separation. According to the Lambert-Beer law, CPMP has the highest molar extinction coefficient of all synthetic chemosensors. A satisfactory separation effect was obtained under a detection wavelength of 278 nm using a carbon-8 column and gradient elution over 14 min, with a flow rate of 1 mL per minute. Glucose (Glc), galactose (Gal), and mannose (Man) make up the majority of the monosaccharide components in PCPs, and their molar ratios are 1.73:0.58:1. The confirmed HPLC method has outstanding precision and accuracy, establishing a quality control method for PCPs. Additionally, the CPMP showed a visual improvement from colorless to orange after the detection of reducing sugars, allowing for further visual analysis.

Material flow analysis and characteristics of multiple-source organic solid wastes from a perspective of ecological network analysis: A case study in Hefei, China.

The numerous resources are consumed and a large number of multiple-source organic solid wastes are discharged during urban metabolic, which put pressures to environment. This study combined material flow analysis and ecological network analysis to comprehensively analyse the metabolism of multiple-source organic solid waste in Hefei. Analysing current metabolic characteristics of urban multiple-source organic solid waste and relationships between the components of metabolic system can help urban environmental management. The internal material flows of the system were analysed by a metabolic network containing 5 nodes and 18 pathways, which revealed metabolic characteristics of multiple-source organic solid waste in Hefei. The study showed that the metabolic system of multiple-source organic solid waste was relatively stable though distribution of internal flows changed in 8 years. The metabolic environment and agricultural sector covered a relatively large weight in this model. The control and exploitation relationships dominated the metabolic system. The urban metabolic mechanism reflected in this research can improve efficiency of urban metabolic resource, optimize waste management and provide data support for sustainable urban development. This study provided scientific guidance for metabolic research in Hefei and similar cities in China's rapid economic development.

Green synthesis of ceramsite from industrial wastes and its application in selective adsorption: Performance and mechanism.

The increasing requirement and consumption of coal has resulted in a large accumulation of coal gangue. The reuse and recycling of coal gangue have become a high priority for sustainable development. A sustainable and efficient ceramsite adsorbent was prepared for copper ions adsorption by using coal gangue, coal fly ash, and copper slag as the main materials. The appropriate performance of the ceramsite could be obtained at a mixture of coal gangue, coal fly ash, and copper slag at a weight ratio of 3:4:1. The optimal sintering temperature and time were 1050 °C and 20 min, respectively. The main crystalline phases of ceramsite were quartz, mullite, and anorthite. Many micropores are connecting the interior on the surface of ceramsite under scanning electron microscope. The maximum copper ions adsorption capacity reached up to 20.6 mg/g at 303 K when pH and time were 5 and 1440 min, respectively. The adsorption kinetics and isotherm could be described by the pseudo-second-order model and Freundlich model, respectively. The adsorption mechanisms of Cu2+ with ceramsite were attributed to Cu(OH)2 precipitation formed on the alkaline surface of ceramsite and complexation reactions occurred between the O-containing groups (including C-O, Fe-O, and Si-O) from ceramsite and Cu2+. The prepared ceramsite may be also applied to other heavy metal wastewater treatments.

Perceived health competence and health education experience predict health promotion behaviors among rural older adults: A cross-sectional study.

BACKGROUND: Health promotion behaviors are key determinant of health and well-being, and also play an important role in promoting successful aging. This study investigated levels of engagement in health promotion behaviors among Chinese rural older adults, and explored effects of perceived health competence, health education activities experience and sociodemographic variables on health promotion behavior in this population. METHODS: A multicenter cross-sectional survey was performed. Participants were recruited by a multistage, stratified, cluster-sampling procedure from Nanbu County, Sichuan Province, China. All participants completed four paper questionnaires: sociodemographic characteristics and health care status survey, the Chinese version of the health promoting lifestyle profile-II (HPLP-II), perceived health competence scale and Lubben social network scale. Data were collected from July to August 2021. Stepwise multiple linear regression analysis was performed to analyze the effects of different factors on health promotion behaviors. RESULTS: A total of 425 rural older adults with an average age of 72.7 years were included in analysis. The overall average score of HPLP-II was 101.6. The stepwise multiple linear regression analysis results showed that those who had higher perceived health competence (ß = 0.66, P < 0.001), experienced health education activities (ß = 0.254, P < 0.001), had physical examination (ß = 0.107, P < 0.001), was married (ß = 0.189, P < 0.001), had primary school education or above (ß = 0.189, P < 0.001), and had a per capita monthly household income of more than 1000¥ (ß = 0.085, P = 0.007), have higher levels of engagement in health promotion behaviors; while the level of health promotion behaviors of the older adults living alone was lower than that of living with their spouse or others (ß = -0.192, P < 0.001). Combination of the above variables accounted for a total of 69.1% of the variance in health promotion behaviors. CONCLUSIONS: The level of health promotion behaviors among Chinese rural older adults is low. Perceived health competence and health education activities experience are two strong determinants of health promotion behaviors. Comprehensive health promotion programs aimed at improving perceived health competences and health literacy through health education activities may be an important part of optimizing the level of health promotion behaviors among rural older adults.

Cognitive function and associated factors in older adults: evidence from the China Health and Retirement Longitudinal Study.

BACKGROUND: Identification of cognition status and its associated factors permit targeted interventions. This study aimed to: (i) investigate cognitive function of Chinese older adults using a large, nationally representative cohort; and (ii) explore its associated factors from aspects of socio-demographic, health behaviour, physical and mental health. METHODS: Data on 2665 adults aged 65 and older from the China Health and Retirement Longitudinal Study wave 4 in 2018 were analyzed. Information on self-reported cognition status, socio-demographic characteristics, health behaviour, physical and mental health status were obtained. Hierarchical regression analyses were conducted to explore associated factors. RESULTS: The cognition score was 24.8, with 41.1% of Chinese older adults identified as cognitively impaired. Better cognition was associated with being married, more education, living in a city/town or urban-rural integration zone, moderate night-time sleep (5-9 h) and post-lunch napping (less than 90 min), moderate/light physical activity for 30 min to 2 h every day, socially active and good health status; while worse cognition was associated with older age, intensive physical activity every day and more than 4 h a day, greater dependency in activities of daily living and depression. CONCLUSIONS: Cognitive impairment is a common health problem in Chinese older adults. Its associated factors are multifaceted, including socio-demographic characteristics, health behaviour and physical and mental health status. Developing interventions focused on these factors may be an important part of optimising cognition in these populations.

[Metabolomic changes of neonatal sepsis: an exploratory clinical study]. / æ–°ç”Ÿå„¿è´¥è¡€ç—‡çš„ä»£è°¢ç»„å­¦æ”¹å˜ï¼šä¸€é¡¹æŽ¢ç´¢æ€§ä¸´åºŠç ”ç©¶.

OBJECTIVES: To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission. METHODS: A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points. RESULTS: On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism. CONCLUSIONS: The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.

Social support, anxiety symptoms, and depression symptoms among residents in standardized residency training programs: the mediating effects of emotional exhaustion.

BACKGROUND: Although studies indicate that social support is related to emotional exhaustion, depression symptoms, and anxiety symptoms, the underlying mechanism between those variables remains unknown. METHODS: Based on a sample of 254 residents in standardized residency training programs, two mediation models were tested in which emotional exhaustion served as a mediator in the relationship between social support and anxiety symptoms/depression symptoms. We used the following self-reported questionnaires as instruments to collect data: zung self-rating depression scale, zung self-rating anxiety scale, social support rating scale, and emotional exhaustion scale. RESULTS: In the final study sample, the mean age of the residents was 25.92 years old (SD =1.88), and a total of 41.3% were male, and 58.7% were female. This current study suggested that social support was proven to be a relevant factor affecting anxiety symptoms and depression symptoms. Particularly, the results also indicated that emotional exhaustion partially mediated the impact of social support on anxiety symptoms and depression symptoms among Chinese residents in the standardized residency training program. CONCLUSIONS: Our study signifies that enhancements in social support and reduction of emotional exhaustion can directly or indirectly affect anxiety symptoms and depression symptoms among Chinese residents in the standardized residency training program. These findings will offer insight for health-sector managers to develop programs aimed at social support and adopt individual-level interventions and organization-level interventions to reduce emotional exhaustion.

LncRNA HCG11/miR-26b-5p/QKI5 feedback loop reversed high glucose-induced proliferation and angiogenesis inhibition of HUVECs.

Acute coronary syndrome caused by the rupture of atherosclerotic plaques is one of the primary causes of cerebrovascular and cardiovascular events. Neovascularization within the plaque is closely associated with its stability. Long non-coding RNA (lncRNA) serves a crucial role in regulating vascular endothelial cells (VECs) proliferation and angiogenesis. In this study, we identified lncRNA HCG11, which is highly expressed in patients with vulnerable plaque compared with stable plaque. Then, functional experiments showed that HCG11 reversed high glucose-induced vascular endothelial injury through increased cell proliferation and tube formation. Meanwhile, vascular-related RNA-binding protein QKI5 was greatly activated. Luciferase reporter assays and RNA-binding protein immunoprecipitation (RIP) assays verified interaction between them. Interestingly, HCG11 can also positively regulated by QKI5. Bioinformatics analysis and luciferase reporter assays showed HCG11 can worked as a competing endogenous RNA by sponging miR-26b-5p, and QKI5 was speculated as the target of miR-26b-5p. Taken together, our findings revered that the feedback loop of lncRNA HCG11/miR-26b-5p/QKI-5 played a vital role in the physiological function of HUVECs, and this also provide a potential target for therapeutic strategies of As.

First evidence showing that Pepper vein yellows virus P4 protein is a movement protein.

BACKGROUND: Plant viruses move through plasmodesmata (PD) to infect new cells. To overcome the PD barrier, plant viruses have developed specific protein(s) to guide their genomic RNAs or DNAs to path through the PD. RESULTS: In the present study, we analyzed the function of Pepper vein yellows virus P4 protein. Our bioinformatic analysis using five commonly used algorithms showed that the P4 protein contains an transmembrane domain, encompassing the amino acid residue 117-138. The subcellular localization of P4 protein was found to target PD and form small punctates near walls. The P4 deletion mutant or the substitution mutant constructed by overlap PCR lost their function to produce punctates near the walls inside the fluorescent loci. The P4-YFP fusion was found to move from cell to cell in infiltrated leaves, and P4 could complement Cucumber mosaic virus movement protein deficiency mutant to move between cells. CONCLUSION: Taking together, we consider that the P4 protein is a movement protein of Pepper vein yellows virus.

Sesquiterpenoids from Cultures of the Basidiomycetes Irpex lacteus.

Eight previously undescribed sesquiterpenoids, tremutins A-H (1-8), together with three known ones (9-11), were isolated from cultures of the basidiomycetes Irpex lacteus. Structures of the new compounds together with absolute configurations were elucidated on the basis of extensive spectroscopic methods, as well as single-crystal X-ray diffractions and equivalent circulating density calculations. Compounds 1 and 2 possess an unusual 6/7-fused ring system that might be derived from a tremulane framework. Compounds 3-7 and 9-11 are tremulane sesquiterpenoids of which 4 and 5 are the first tremulane examples with a 1,2-epoxy moiety to be reported. Compounds 6, 7, 10, and 11 possess weak activities to several human cancer cell lines. Compound 8 shows a weak inhibitory effect on NO production with a half maximal inhibitory concentration (IC50) value of 22.7 µM. Compound 1 inhibits the lipopolysaccharide (LPS)-induced proliferation of B lymphocyte cells with an IC50 value of 22.4 µM, while 2 inhibits concanavalin A (Con A)-induced T cell proliferation and LPS-induced B lymphocyte cell proliferation with IC50 values of 16.7 and 13.6 µM, respectively.

[Application of magnetic resonance diffusion tensor imaging in bilirubin-induced neurological dysfunction in neonates].

OBJECTIVE: To study the value of fractional anisotropy (FA) of regions of interest (ROI) on magnetic resonance diffusion tensor imaging (DTI) in bilirubin-induced neurological dysfunction in neonates. METHODS: A total of 91 neonates with hyperbilirubinemia who were hospitalized from January 2017 to January 2018 were enrolled. According to the peak level of total serum bilirubin, they were divided into three groups: mild/moderate increase (n=45), severe increase (n=35), and extremely severe increase (n=11). According to the presence or absence of abnormal neurological manifestations, they were divided into two groups: neurological dysfunction (n=20) and non-neurological dysfunction (n=71). Ten healthy full-term infants were enrolled as the control group. Head DTI was performed for all neonates to measure the FA values of the bilateral globus pallidus, the anterior limb of the internal capsule, the posterior limb of the internal capsule, and the cerebellar dentate nucleus. RESULTS: The extremely severe increase group had significantly lower FA values of the globus pallidus than the control, mild/moderate increase, and severe increase groups (P<0.05). The severe increase group had significantly lower FA values of the globus pallidus than the control group (P<0.05). The extremely severe increase group had significantly lower FA values of the posterior limb of the internal capsule than the control, mild/moderate increase, and severe increase groups (P<0.05). The neurological dysfunction group had significantly lower FA values of the globus pallidus and the posterior limb of the internal capsule than the non-neurological dysfunction group (P<0.05). CONCLUSIONS: Serum bilirubin level combined with the changes in the DTI FA values of the globus pallidus and the posterior limb of the internal capsule can be used to predict the injury of cerebral nuclei and white matter fibers.

Cellulomonas macrotermitis sp. nov., a chitinolytic and cellulolytic bacterium isolated from the hindgut of a fungus-growing termite.

To investigate the symbiotic roles of the gut microbiota in the fungus-growing termite Macrotermes barneyi, a novel strain with chitinolytic and cellulolytic activity, designated strain an-chi-1T, was isolated from the hindgut of M. barneyi. Strain an-chi-1T grows optimally at 28-30 °C, pH 8.0 in PYG medium. On the basis of 16S rRNA gene sequence analysis, this isolate belongs to the genus Cellulomonas with high sequence similarity to Cellulomonas iranensis (99.4%), followed by Cellulomonas flavigena (98.4%), Cellulomonas phragmiteti (97.4%), Cellulomonas oligotrophica (97.2%) and Cellulomonas terrae (97.0%). The DNA-DNA relatedness between an-chi-1T and the type strains of C. iranensis and C. flavigena DSM20109T are 35.4% and 23.7%, respectively. The major cellular fatty acids are anteiso-C15:0 and C14:0. The polar lipid profile consists of diphosphatidylglycerol, phosphatidylinositol mannosides, phosphatidylinositol dimannosides and one unidentified phospholipid. The cell-wall sugar is ribose. The peptidoglycan contains glutamic acid, aspartic acid and alanine. The DNA G+C content is 67.3 mol%. Based on its distinctive phenotypic, phylogenetic, and chemotaxonomic characteristics, an-chi-1T represents a novel species of the genus Cellulomonas, for which the name Cellulomonas macrotermitis sp. nov. is proposed. The type strain is an-chi-1T (= JCM 31923T = CICC 24195T).

Unique Domain Structure of Two-Dimensional α-Mo2C Superconducting Crystals.

The properties of two-dimensional (2D) materials such as graphene and monolayer transition metal dichalcogenides are strongly influenced by domain boundaries. Ultrathin transition metal carbides are a class of newly emerging 2D materials that are superconducting and have many potential applications such as in electrochemical energy storage, catalysis, and thermoelectric energy conversion. However, little is known about their domain structure and the influence of domain boundaries on their properties. Here we use atomic-resolution scanning transmission electron microscopy combined with large-scale diffraction-filtered imaging to study the microstructure of chemical vapor deposited high-quality 2D α-Mo2C superconducting crystals of different regular shapes including triangles, rectangles, hexagons, octagons, nonagons, and dodecagons. The Mo atom sublattice in all these crystals has a uniform hexagonal closely packed arrangement without any boundaries. However, except for rectangular and octagonal crystals, the C atom sublattices are composed of three or six domains with rotational-symmetry and well-defined line-shaped domain boundaries because of the presence of three equivalent off-center directions of interstitial carbon atoms in Mo octahedra. We found that there is very small lattice shear strain across the domain boundary. In contrast to the single sharp transition observed in single-domain crystals, transport studies across domain boundaries show a broad resistive superconducting transition with two distinct transition processes due to the formation of localized phase slip events within the boundaries, indicating a significant influence of the boundary on 2D superconductivity. These findings provide new understandings on not only the microstructure of 2D transition metal carbides but also the intrinsic influence of domain boundaries on 2D superconductivity.

Inhibition of P38 MAPK Downregulates the Expression of IL-1ß to Protect Lung from Acute Injury in Intestinal Ischemia Reperfusion Rats.

Acute lung injury (ALI) induced by intestinal ischemia/reperfusion (II/R) has high incidence and mortality, in which IL-1ß was essential for the full development of ALI. However, the detailed regulating mechanism for this phenomenon remains to be unclear. The purpose of this study was to investigate whether inhibition of P38 MAPK could downregulate the expression of IL-1ß to protect lung from acute injury in II/R rats. Here, we found that the level of pulmonary edema at 16 hours after operation (hpo) was obviously enhanced compared to that in 8hpo and sham groups. Immunofluorescent staining demonstrated that IL-1ß and P38 MAPK were detected in lung tissues. And rats with II/R have the highest translation level for IL-1ß and phosphorylation of P38 MAPK in lung tissues at 16hpo compared with 8hpo and sham groups. Moreover, administration of SB239063, an inhibitor of P38 α and ß, could effectively downregulate the expressions of IL-1ß and protects lung tissues from injury in II/R rats. Our findings indicate that the inhibition of P38 α and ß may downregulate the expression of IL-1ß to protect lung from acute injury in II/R, which could be used as a potential target for reducing ALI induced by II/R in the future clinical trial.

Multiple mechanisms involved in diabetes protection by lipopolysaccharide in non-obese diabetic mice.

Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually ß cell loss in the course of type 1 diabetes (T1D) development. However, according to the "hygiene hypothesis", bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention. Further, LPS administration suppressed spleen T lymphocyte proliferation, increased the generation of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), reduced the synthesis of strong Th1 proinflammatory cytokines, and downregulated TLR4 and its downstream MyD88-dependent signaling pathway. Most importantly, multiple injections of LPS induced a potential tolerogenic dendritic cell (DC) subset with low TLR4 expression without influencing the DC phenotype. Explanting DCs from repeated LPS-treated NOD mice into NOD/SCID diabetic mice conferred sustained protective effects against the progression of diabetes in the recipients. Overall, these results suggest that multiple mechanisms are involved in the protective effects of LPS against the development of diabetes in NOD diabetic mice. These include Treg induction, down-regulation of TLR4 and its downstream MyD88-dependent signaling pathway, and the emergence of a potential tolerogenic DC subset.

Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis.

BACKGROUND: Regenerating islet-derived 3 (Reg3) is abnormally expressed in several human digestive system diseases, including chronic pancreatitis (CP) and pancreatic cancer (PC). AIM: The purpose of this study was to clarify the mechanism of the enhanced expression of Reg3 in inflammation-induced PC. METHODS: C57BL/6 mice were treated with caerulein for 6 weeks to induce CP and then injected with pReg3g--a lentivirus system encoding for murine Reg3g--accompanied by dimethylbenzanthracene to induce PC. We detected pancreatic histopathological characteristics, tumor-related gene expression, inflammation-associated pathway activation, serum biochemical indicators, and immunological cell activities. RESULTS: The mice that developed CP after caerulein treatment were marked by pronounced histologic lesions, elevated serum amylase levels, and activation of inflammation-related pathways. Mice given a high dose of pReg3g developed PC by 16 weeks, with recognizable tumors in the pancreas. While, both the low and high doses of pReg3g produced higher transcription of c-fos, k-ras, cytokeratin-19, and proliferating cell nuclear antigen, and a lower expression of caspase-3 compared to pNEG controls. Additionally, the higher dose of pReg3g increased the expressions of pSTAT3, NFκB (p65), and SOCS3 methylation during PC development. In addition, mice treated with pReg3g displayed higher levels of serum IL10 and TGFß and suppressed T lymphocyte proliferation and DC function. CONCLUSION: The comprehensive analysis suggests enhanced Reg3g expression exacerbates PC in inflammation-associated cancer progression. Reg3g appears to promote CP-related PC in mice through multiple mechanisms, involving enhanced transcription of pancreatic tumor markers, repression of anti-tumor immunity, and activation of STAT3/p65 signal transduction pathways.