Optimizing the Mulching Pattern and Nitrogen Application Rate to Improve Maize Photosynthetic Capacity, Yield, and Nitrogen Fertilizer Utilization Efficiency.

Residual film pollution and excessive nitrogen fertilizer have become limiting factors for agricultural development. To investigate the feasibility of replacing conventional plastic film with biodegradable plastic film in cold and arid environments under nitrogen application conditions, field experiments were conducted from 2021 to 2022 with plastic film covering (including degradable plastic film (D) and ordinary plastic film (P)) combined with nitrogen fertilizer 0 (N0), 160 (N1), 320 (N2), and 480 (N3) kg·ha-1. The results showed no significant difference (p > 0.05) in dry matter accumulation, photosynthetic gas exchange parameters, soil enzyme activity, or yield of spring maize under degradable plastic film cover compared to ordinary plastic film cover. Nitrogen fertilizer is the main factor limiting the growth of spring maize. The above-ground and root biomass showed a trend of increasing and then decreasing with the increase in nitrogen application level. Increasing nitrogen fertilizer can also improve the photosynthetic gas exchange parameters of leaves, maintain soil enzyme activity, and reduce soil pH. Under the nitrogen application level of N2, the yield of degradable plastic film and ordinary plastic film coverage increased by 3.74~42.50% and 2.05~40.02%, respectively. At the same time, it can also improve water use efficiency and irrigation water use efficiency, but it will reduce nitrogen fertilizer partial productivity and nitrogen fertilizer agronomic use efficiency. Using multiple indicators to evaluate the effect of plastic film mulching combined with nitrogen fertilizer on the comprehensive growth of spring maize, it was found that the DN2 treatment had the best complete growth of maize, which was the best model for achieving stable yield and income increase and green development of spring maize in cold and cool irrigation areas.

Photosynthetic characteristics, yield and quality of sunflower response to deficit irrigation in a cold and arid environment.

In arid regions, deficit irrigation stands as an efficacious strategy for augmenting agricultural water conservation and fostering sustainable crop production. The Hexi Oasis, an irrigation zone situated in Northwest China, serves as a pivotal area to produce grain and cash crops. Nonetheless, due to the predominant conditions of low rainfall and high evaporation, the scarcity of irrigation water has emerged as a critical constraint affecting crop growth and yield in the area. In order to evaluate the effects of deficit irrigation on photosynthetic characteristics, yield, quality, and water use efficiency of sunflower, a two-year field experiment with under-mulched drip irrigation was conducted in the cold and arid environment of the Hexi Oasis region. Water deficits were implemented at sunflower seedling and maturity and consisted of three deficit levels: mild deficit (65-75% field capacity, FC), moderate deficit (55-65% FC), and severe deficit (45-55% FC). A total of six combined water deficit treatments were applied, using full irrigation (75-85% FC) throughout the entire crop-growing season as the control (CK). The results illustrated that water deficit engendered a decrease in leaf net photosynthetic rate, transpiration rate, and stomatal conductance of sunflower compared to CK, with the decrease becoming significant with the water deficit increasing. A mild water deficit, both at the seedling and maturity phases, precipitated a significant enhancement (p< 0.05) in leaf water use efficiency. Under mild water deficit, stomatal limitation emerged as the predominant factor inducing a reduction in the photosynthetic capacity of sunflower leaves, while as the water deficit escalated, non-stomatal limitation progressively assumed dominance. Moreover, a mild/moderate water deficit at seedling and a mild water deficit at maturity (WD1 and WD3) significantly improved sunflower seed quality under consistent yield conditions and significantly increased irrigation water use efficiency, with an average increase of 15.3% and 18.5% over the two years, respectively. Evaluations utilizing principal component analysis and membership function methods revealed that WD1 attained the highest comprehensive score. Consequently, a mild water deficit at both seedling and maturity (WD1) is advocated as the optimal deficit irrigation strategy for sunflower production within the cold and arid environment of Northwest China.

Crop coefficient determination and evapotranspiration estimation of watermelon under water deficit in a cold and arid environment.

To investigate the evapotranspiration and crop coefficient of oasis watermelon under water deficit (WD), mild (60%-70% field capacity, FC)and moderate (50%-60% FC) WD levels were set up at the various growth stages of watermelon, including seedling stage (SS), vine stage (VS), flowering and fruiting stage (FS), expansion stage (ES), and maturity stage (MS), with adequate water supply (70%-80% FC) during the growing season as a control. A two-year (2020-2021) field trial was carried out in the Hexi oasis area of China to explore the effect of WD on watermelon evapotranspiration characteristics and crop coefficient under sub-membrane drip irrigation. The results indicated that the daily reference crop evapotranspiration showed a sawtooth fluctuation which was extremely significantly and positively correlated with temperature, sunshine hours, and wind speed. The water consumption during the entire growing season of watermelon varied from 281-323 mm (2020) and 290-334 mm (2021), among which the phasic evapotranspiration valued the maximum during ES, accounting for 37.85% (2020) and 38.94% (2021) in total, followed in the order of VS, SS, MS, and FS. The evapotranspiration intensity of watermelon increased rapidly from SS to VS, reaching the maximum with 5.82 mm·d-1 at ES, after which it gradually decreased. The crop coefficient at SS, VS, FS, ES, and MS varied from 0.400 to 0.477, from 0.550 to 0.771, from 0.824 to 1.168, from 0.910 to 1.247, and from 0.541 to 0.803, respectively. Any period of WD reduced the crop coefficient and evapotranspiration intensity of watermelon at that stage. And then the relationship between LAI and crop coefficient can be characterized better by an exponential regression, thereby establishing a model for estimating the evapotranspiration of watermelon with a Nash efficiency coefficient of 0.9 or more. Hence, the water demand characteristics of oasis watermelon differ significantly during different growth stages, and reasonable irrigation and water control management measures need to be conducted in conjunction with the water requirements features of each growth stage. Also, this work aims to provide a theoretical basis for the irrigation management of watermelon under sub-membrane drip irrigation in desert oases of cold and arid environments.

Antimicrobial peptide MPX attenuates LPS-induced inflammatory response and blood-testis barrier dysfunction in Sertoli cells.

Orchitis accounts for a high proportion of male animal reproductive disorders. Hence, it is urgent to identify drugs for the prevention and treatment of orchitis. Antimicrobial peptides (AMPs) are currently recognized as one of the most promising alternatives to antibiotics. However, the protective effects of AMPs on lipopolysaccharide (LPS)-induced orchitis have not been reported. In this study, we developed an LPS-induced orchitis model in which primary bovine Sertoli cells were used as model cells. MPX was indicated to effectively reduce the inflammatory response of Sertoli cells. MPX attenuated the gene expression of the proinflammatory cytokines TNF-α, IL-6 and IL-1ß by suppressing the MAPK pathway, especially the phosphorylation of p38 and ERK. MPX also decreased the oxidative stress response caused by LPS and upregulated Occludin and Claudin-1 expression, thereby maintaining the integrity of the blood-testis barrier. Moreover, we found that MPX inhibited apoptosis in Sertoli cells. In a mouse model, we found that MPX significantly inhibited the disruptive effects of LPS, reducing seminiferous epithelium damage, vacuolations, hyperplasia, and apoptosis in spermatogenic cells and rescuing spermatogenesis. In addition, the expression of inflammatory factors such as IL-1ß, IL-18, IL-6 and TNF-α was decreased after MPX treatment in the mouse testes. MPX had no effect on other organs in mice, indicating its safety. This study was undertaken to investigate how MPX regulates the inflammatory response in Sertoli cells and provide a reference for the clinical prevention and treatment of male animal orchitis.

Effects of water and nitrogen coupling on the photosynthetic characteristics, yield, and quality of Isatis indigotica.

Isatis indigotica is a commercial medicinal crop that is widely cultivated with high water and nutrient application, in the arid areas of northwest China. Rational irrigation and nitrogen application are key factors for successful crop management. The objective of this study was to determine the effect of water and nitrogen coupling on the photosynthetic characteristics, yield, and quality of Isatis indigotica produced in northwestern China. Field trials were conducted for 2 consecutive years at an irrigation test station. Data on photosynthetic parameters, yield, and quality were collected from individual Isatis indigotica for each treatment during 2018-2019. The application of nitrogen significantly increased photosynthetic rates and yield under the same irrigation conditions. However, the yields were reduced in the excess water treatments (W3N1 and W3N2) and in the excess nitrogen treatments (W1N3, W2N3, and W3N3) in contrast to the optimum W2N2 treatment. Moreover, the quality indicators of the W2N2 treatment decreased compared with CK, which was due to water stress and more photoassimilates being available to the roots, but the effective quality index value could be effectively improved by greatly increasing the yield.

Establishment and comparison of Actinobacillus pleuropneumoniae experimental infection model in mice and piglets.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia, a disease responsible for substantial losses in the worldwide pig industry. In this study, outbred Kunming (KM) and Institute of Cancer Research (ICR) mice were evaluated as alternative mice models for APP research. After intranasal infection of serotype 5 reference strain L20, there was less lung damage and a lower clinical sign score in ICR compared to KM mice. However, ICR mice showed more obvious changes in body weight loss, the amount of immune cells (such as neutrophils and lymphocytes) and cytokines (such as IL-6, IL-1ß and TNF-α) in blood and bronchoalveolar lavage fluid (BALF). The immunological changes observed in ICR mice closely mimicked those found in piglets infected with L20. While both ICR and KM mice are susceptible to APP and induce pathological lesions, we suggest that ICR and KM mice are more suitable for immunological and pathogenesis studies, respectively. The research lays the theoretical basis for determine that mice could replace pigs as the APP infection model and it is of significance for the study of APP infection in the laboratory.

Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells.

Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

A corn straw-based diet increases release of inflammatory cytokines in peripheral blood mononuclear cells of dairy cows.

Recent studies have shown that diet can affect the body's immunity. Roughage of dairy cows consists of a variety of plant materials which make different contributions to health. This study investigated the effect of different roughages on the immunity of dairy cows. Serum, peripheral blood mononuclear cells (PBMCs), and milk samples were collected from 20 multiparous mid-lactation cows fed mixed forage (MF)- or corn straw (CS)-based diets. Expression profile analysis was used to detect the differentially expressed genes (DEGs) from PBMCs. The results showed that milk protein in the MF group increased to 3.22 g/100 ml, while that of the CS group milk was 2.96 g/100 ml; by RNA sequencing, it was found that 1615 genes were differentially expressed between the CS group and the MF group among the 24 027 analyzed probes. Gene ontology (GO) and pathway analysis of DEGs suggested that these genes (especially genes coding cytokines, chemokine and its receptors) are involved in the immune response. Results were confirmed at the protein level via detecting the levels of interleukin-2 (IL-2), IL-6, IL-10, IL-12, leptin (LEP), interferon-γ (IFN-γ), transforming growth factor-ß1 (TGF-ß1), and tumor necrosis factor-α (TNF-α) in peripheral blood by enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay analysis. Our data supported the conclusions that the protein content in milk of the MF group was higher than that of the CS group, the CS-based diets induced more release of cytokines than the MF-based diets in dairy cows' PBMCs, and milk protein content may be affected by cytokines.

MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota.

The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes. High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes, Blautia, Coprococcus_1, and Ruminococcus_1. Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes, indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.

Human adipose-derived mesenchymal stem cells and synovial-derived mesenchymal stem cells synergistically inhibit the degeneration of inflammatory chondrocytes / 中国组织工程研究

BACKGROUND: Intra-articular injection of cells targeting to change the microenvironment in lesions can act on early osteoarthritis of inflammatory chondrocytes. Implanted cells affect the progress of the disease by the cell characteristics. OBJECTIVE: To explore the synergistic effect of mesenchymal stem cells from human knee adipose (ADMSCs) and synovial tissues (SDMSCs) to inhibit the degeneration of inflammatory chondrocytes. METHODS: ADMSCs, SDMSCs and inflammatory chondrocytes were primary cultured. Under in vitro two-dimensional culture conditions, cell proliferation assay (MTS) was performed to detect the proliferation of three kinds of cells. Differences in chondrogenic markers at mRNA and protein levels between three kinds of adherent cells were detected by quantitative PCR and immunofluorescence. Under in vitro three-dimensional mixed culture conditions, three groups were set up: (1) ADMSCs+inflammatory chondrocytes (A+C group), (2) SDMSCs+inflammatory chondrocytes (S+C group), and (3) ADMSCs-SDMSCs+inflammatory chondrocytes (A+S+C group). Alcian blue staining, safranin O staining and type Ⅱ collagen immunohistochemistry staining were performed on the mixed-cultured cell mass paraffin sections followed by quantitative analysis. Chondrogenic differentiation in each group was detected by quantitative PCR. Culture supernatants were collected to detect the secretion of pro-inflammatory and anti-inflammatory factors by enzyme-linked immunosorbent assay. RESULTS AND CONCLUSION: Under the two-dimensional culture, the proliferative rate of ADMSCs was significantly higher than that of inflammatory chondrocytes and SDMSCs (P < 0.05). The expression of type Ⅱ collagen mRNA and protein and proteoglycan protein in inflammatory chondrocytes was significantly higher than that in the other two kinds of cells (P < 0.01). Under the three-dimensional culture, the percentage of chondrogenic area per total area was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). The expression of type Ⅱ collagen and proteoglycan was significantly higher in the A+S+C group than the S+C and A+C groups (P < 0.05). Compared with the other two groups, the S+C group showed higher levels of interleukin 1, interleukin 6, and tumor necrosis factor α, but lower level of interleukin 10 (P < 0.05). To conclude, the combined use of ADMSCs and SDMSCs synergistically inhibits the degeneration of inflammatory chondrocytes.

An anti-Propionibacterium acnes antibody shows heterologous resistance to an Actinobacillus pleuropneumoniae infection independent of neutrophils in mice.

Porcine contagious pleuropneumonia is a highly fatal respiratory disease that is caused by Actinobacillus pleuropneumoniae (APP) and results in tremendous economic losses for the pig breeding industry worldwide. Previous studies have demonstrated that Propionibacterium acnes (PA) could effectively prevent APP infection in mice and pigs. The humoral immune response played a primary role during this process and anti-PA antibody could mediate macrophages to kill the bacteria. However, the role of neutrophils in this process is currently unknown. In this study, mice were injected with cyclophosphamide to deplete neutrophils and then passively immunized with anti-PA serum or negative serum. Mice were subsequently challenged with APP serotype 1. The results showed that the mice exhibited less bacterial colonization, less lung damage, and a high survival rate, which were immunized with the anti-PA antibody whether neutrophils were depleted or not. Worse still, the presence of neutrophils increased the damage to the mice after challenge. These results suggest that the activity of the anti-PA antibody against APP infection was independent of neutrophils. These findings have important significance for understanding the mechanisms of humoral immunity conferred by heterologous immunization and lay a good foundation for preventing APP infection.

Research Progress of Anti-allergy Natural Products / 中国药学杂志

Based on overseas and domestic data bank mainly as Scifinder, ACS publication, CNKI, and CQVIP. The relationships between the types of natural products and their anti-allergic activities have been summarized. The advances of anti-allergic natural products over the past ten years have been reviewed. The pathogenesis of allergic diseases and the diversity of anti-allergy components and natural products were summarized, together with their origins and mechanisms of anti-allergy activities. Many natural products show multiple anti-allergy targets and few side effects, while the research is still far from enough. Several suggestions were proposed for further research on anti-allergy natural medicines on the basis of our review.

Risk factors of early surgical intervention in Crohn's disease patients with spontaneous intra-abdominal abscess / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the risk factors of early surgical intervention in Crohn's disease (CD) patients with spontaneous intra-abdominal abscess.</p><p><b>METHODS</b>Clinical data of 94 CD patients with spontaneous intra-abdominal abscess admitted to The Sixth Affiliated Hospital of Sun Yat-sen University between May 2008 and Dec 2015 were analyzed retrospectively. Univariate and multivariate analysis were applied to evaluate the early surgery risk of CD patients with spontaneous intra-abdominal abscess using logistic regression model.</p><p><b>RESULTS</b>A total of 94 eligible patients were identified from our registry, including 70 males and 24 females. The mean age at the diagnosis of CD and at development of abscess was 28.4 years and 30.4 years old, respectively. The median duration of CD between the diagnosis and development of an abscess was 3 years. According to the Montreal classification, L3 (ileocolonic) was the most common disease location (81.9%) in these patients. Most of the patients(76.6%) developed a single abscess, while multiple abscesses were detected in 22 patients(23.4%). Forty-four patients(46.8%) underwent surgery within 60 days after hospitalization due to spontaneous intra-abdominal abscess complicating CD. Multivariate logistic regression analysis revealed that history of abdominal surgery(OR=3.23, 95%CI:1.12 to 9.31, P=0.030), concomitant intestinal stenosis (OR=3.52, 95%CI:1.26 to 9.85, P=0.017) and concomitant intestinal fistula (OR=4.31, 95%CI:1.25 to 14.80, P=0.020) were the independent risk factors of early surgical intervention, while enteral nutrition (OR=0.18, 95%CI:0.05 to 0.62, P=0.007) was the independent protective factor.</p><p><b>CONCLUSIONS</b>Nearly half of CD patients with spontaneous intra-abdominal abscess will undergo early surgical intervention. Patients with history of abdominal surgery, concomitant intestinal stenosis and concomitant intestinal fistula have higher risk of early surgical intervention, and appropriate application of enteral nutrition may reduce the risk.</p>

Historical evolution and current concepts of surgical treatment for inflammatory bowel diseases / 中华胃肠外科杂志

Patients with inflammatory bowel disease (IBD) may require surgical intervention for refractory disease or complications. Prompt surgery and appropriate surgical procedures are critical when surgery is indicatedd. With continuous optimization and innovation of surgical procedures, there have been significant changes in the concepts and operations of IBD in the past century. Learning the evolution of surgical treatment for IBD could help us understand the rationale, indications, and pertinent techniques of surgical procedures. Innovations are emerging in IBD management including the advent of biological agents, laparoscopy, and multi-disciplinary team approach, it is imperative for IBD specialist to learn the state-of-the-art knowledge.

Surgical management of inflammatory bowel disease in China: a systematic review of two decades

BACKGROUND/AIMS: The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China. METHODS: We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures. RESULTS: A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010. CONCLUSIONS: The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.

Surgical management of inflammatory bowel disease in China: a systematic review of two decades

BACKGROUND/AIMS: The past decades have seen increasing incidence and prevalence of inflammatory bowel disease (IBD) in China. This article aimed to summarize the current status and characteristics of surgical management for IBD in China. METHODS: We searched PubMed, Embase, and Chinese databases from January 1, 1990 to July 1, 2014 for all relevant studies on the surgical treatment IBD in China. Eligible studies with sufficient defined variables were further reviewed for primary and secondary outcome measures. RESULTS: A total of 74 studies comprising 2,007 subjects with Crohn's disease (CD) and 1,085 subjects with ulcerative colitis (UC) were included. The percentage of CD patients misdiagnosed before surgery, including misdiagnosis as appendicitis or UC, was 50.8%±30.9% (578/1,268). The overall postoperative complication rate was 22.3%±13.0% (267/1,501). For studies of UC, the overall postoperative complication rate was 22.2%±27.9% (176/725). In large research centers (n>50 surgical cases), the rates of emergency operations for CD (P=0.032) and in-hospital mortalities resulting from both CD and UC were much lower than those in smaller research centers (n≤50 surgical cases) (P=0.026 and P <0.001, respectively). Regarding the changes in CD and UC surgery over time, postoperative complications (P=0.045 for CD; P=0.020 for UC) and postoperative in-hospital mortality (P=0.0002 for CD; P=0.0160 for UC) both significantly improved after the year 2010. CONCLUSIONS: The surgical management of IBD in China has improved over time. However, the rates of misdiagnosis and postoperative complications over the past two decades have remained high. Large research centers were found to have relatively better capacity for surgical management than the smaller ones. Higher quality prospective studies are needed in China.

Contemplation on the application of big data in clinical medicine / 中华胃肠外科杂志

Medicine is another area where big data is being used. The link between clinical treatment and outcome is the key step when applying big data in medicine. In the era of big data, it is critical to collect complete outcome data. Patient follow-up, comprehensive integration of data resources, quality control and standardized data management are the predominant approaches to avoid missing data and data island. Therefore, establishment of systemic patients follow-up protocol and prospective data management strategy are the important aspects of big data in medicine.

Experimental study of adipose-derived mesenchymal stem cells in the treatment of Crohn's disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the efficacy of adipose-derived mesenchymal stem cells (ADMSCs) in a murine model of inflammatory bowel disease, and its potential mechanism.</p><p><b>METHODS</b>Murine colitis mouse model of Crohn's disease(CD) was created by trinitrobenzene sulfonic acid(TNBS)-induced colitis. Seventy-five 6-8 weeks female BALB/c mice were randomly divided into 3 groups: control group, TNBS group and ADMSC group. To verify the therapeutic effect of ADMSC, real-time PCR and immunohistochemical staining were performed to measure inflammatory cytokines levels in colon tissues. The 10-day survival statuses were recorded after the infusion of ADMSCs.</p><p><b>RESULTS</b>Intraperitoneal injection of ADMSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and increased survival(60% vs. 30%, P<0.05) in the TNBS-induced mouse model of CD. Compared with TNBS group, proinflammatory cytokines, including TNF-α, IL-12 and VEGF of ADMSC group were significantly reduced, with significant increase of IL-10 expression.</p><p><b>CONCLUSION</b>ADMSCs can effectively repair the injury of colonitis through down-regulation of proinflammatory cytokines TNF-α, IL-12 and VEGF expression, and up-regulation of anti-inflammatory cytokine IL-10 expression, which may be a potential new alternative of cell-based therapy for CD.</p>

BHBA suppresses LPS-induced inflammation in BV-2 cells by inhibiting NF-κB activation.

ß-Hydroxybutyric acid (BHBA) has neuroprotective effects, but the underlying molecular mechanisms are unclear. Microglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The current study investigates the potential mechanisms whereby BHBA affects the expression of potentially proinflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS). The results showed that BHBA significantly reduced LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1ß, and IL-6. Blocking of GPR109A by PTX resulted in a loss of this anti-inflammatory effect in BV-2 cells. Western blot analysis showed that BHBA reduced LPS-induced degradation of IκB-α and translocation of NF-κB, while no effect was observed on MAPKs phosphorylation. All results imply that BHBA significantly reduces levels of proinflammatory enzymes and proinflammatory cytokines by inhibition of the NF-κB signaling pathway but not MAPKs pathways, and GPR109A is essential to this function. Overall, these data suggest that BHBA has a potential as neuroprotective drug candidate in neurodegenerative diseases.

Efficacy and oncological safety of bone marrow mesenchymal stem cell transplantation for colitis in inflammatory bowel disease models in mice / 中国组织工程研究

BACKGROUND:Transfusion of bone marrow mesenchymal stem cells may become a novel and effective biological therapy for inflammatory bowel disease in clinical practice. Nevertheless, the oncological safety of the treatment is worrisome, and is a key to determine whether mesenchymal stem cells can be widely used in treatment of inflammatory bowel disease, and deserves further investigation. OBJECTIVE:To evaluate the therapeutic effect of bone marrow mesenchymal stem celltransfusion against inflammatory bowel disease in mouse models, and to clarify the effects of mesenchymal stem cells on tumorigenesis of inflammatory bowel disease. METHODS:Mouse model of colitis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium. Syngeneic bone marrow mesenchymal stem cells were transfused into mouse model through caudal vein. The therapeutic effect of mesenchymal stem cells was compared and observed, and pathological remission of colitis was evaluated. Mouse model of colitis-driven colon carcinogenesis was established using Balb/c (H-2d) mice exposed to dextran sulfate sodium and azoxymethane. Tumor formation within the murine colon was compared and observed after transfusion of mesenchymal stem cells. RESULTS AND CONCLUSION:In models of dextran sulfate sodium-induced colitis, weight loss and fecal occult blood were lessened in the bone marrow mesenchymal stem cellgroup compared with the phosphate buffered saline group. Histological damage score of colitis was less in the bone marrow mesenchymal stem cellgroup:mucosal structure of distal colon was almost intact under microscope, and there was smal area of epithelial defects and cryptal defects. Inflammatory cellinfiltration, proliferation of capil ary and smal vessels could be observed in mucosa and submucosa. Homing and colonization of mesenchymal stem cells in submucosa of inflamed colon could also be observed by in vivo tracing. In the dextran sulfate sodium/azoxymethane model of colitis-driven colon carcinogenesis, the number of intestinal tumors and tumor load were obviously less in the bone marrow mesenchymal stem cellgroup than in the control group. Results indicated that transfusion of bone marrow mesenchymal stem cells can apparently improve colitis lesions of mice with inflammatory bowel disease and inhibit carcinogenesis of colitis, which may provide theoretical support for the biological safety of mesenchymal stem cells transplantation for inflammatory bowel disease.