第6卷，第2期

The emergence of antibiotic resistant bacteria in the healthcare is a serious concern. In the Healthcare premises precisely intensive care unit are major sources of microbial diversity. Recent findings have demonstrated not only microbial diversity but also drug resistant microbes largely habitat in ICU. Pseudomonas aeruginosa found as a part of normal intestinal flora and a significant pathogen responsible for wide range of ICU acquired infection in critically ill patients. Nosocomial infection associated with this organism including gastrointestinal infection, urinary tract infections and blood stream infection. Infection caused by this organism are difficult to treat because of the presence of its innate resistance to many antibiotics (β-lactam and penem group of antibiotics), and its ability to acquire further resistance mechanism to multiple class of antibiotics, including Beta-lactams, aminoglycosides and fluoroquinolones. In the molecular evolution microbes adopted several mechanism to maintain genomic plasticity. The tool microbe use for its survival is mainly biofilm formation, quorum sensing, and horizontal gene transfer and enzyme promiscuity. Such genomic plasticity provide an ideal habitat to grow and survive in hearse environment mainly antibiotics pressure. This review focus on infection caused by Pseudomonas aeruginosa, its mechanisms of resistance and available treatment options. The present study provides a systemic review on major source of Pseudomonas aeruginosa in ICU. Further, study also emphasizes virulence gene/s associated with Pseudomonas aeruginosa genome for extended drug resistance. Study gives detailed overview of antibiotic drug resistance mechanism.

1312

Breast cancer is the second highest prevalent cancer globally after lung cancer with 2.09 million cases during 2018. Adults about 1.9 billion were overweight and over 650 million out of these were obese during 2016. There is a significant relationship between breast cancer risk and obesity. Premature menopause and premenopausal obesity diminish the risk whereas postmenopausal obesity amplifies the risk, because adipose tissue acts as the major reservoir for estrogen biosynthesis after menopause. Lofty estrogen levels in serum along with enhanced peripheral site production of estrogen have been viewed as major reasons of developing breast cancer in overweight postmenopausal women. This review explains body fat as a peripheral site for estrogen biosynthesis, estrogen exposure affecting body fat distribution, and the mechanism of estrogen production from body fats.

1219

Parkinson's disease (PD) is the second most common age related neurodegenerative disorder worldwide and presents as a progressive movement disorder. Globally seven million to 10 million people have Parkinson's disease. Parkinsonism is typically sporadic in nature. Loss of dopaminergic neurons from substantia nigra pars compacta (SNpc) and the neuronal intracellular Lewy body inclusions are the major cause of PD. Gene mutation and protein aggregation play a pivotal role in the degeneration of dopamine neurons. But the actual cause of dopamine degeneration remains unknown. However, several rare familial forms of PD are associated with genetic loci, and the recognition of causal mutations has provided insight into the disease process. Yet, the molecular pathways and gene transformation that trigger neuronal susceptibility are inadequately comprehended. The discovery of a mutation in new genes has provided a basis for much of the ongoing molecular work in the PD field and testing of targeted therapeutics. Single gene mutation in a dominantly or recessively inherited gene results a great impact in the development of Parkinson's disease. In this review, we summarize the molecular genetics of PD.

1205

Extracellular vesicles (EVs) are vesicle-like substances released by eukaryotic cells. Based on their origin and size, EVs are mainly divided into exosomes, microvesicles and apoptotic bodies, and they are secreted by eukaryotic cells under physiological and pathological conditions. EVs are enriched with nucleic acids, proteins and other factors. EVs can regulate the function of adjacent and distant cells, and they are even involved in the pathogenesis of diseases. They contain proteins associated with the pathogenesis of neurodegenerative diseases (NDs), such as the α-synuclein (α-syn) and tau proteins, which suggest potential roles for EVs as biomarkers and carriers of drugs and other therapeutic molecules that can cross the bloodebrain barrier to treat NDs. In this review, we summarized the function of EVs in the pathogenesis of different NDs and related advances in EVs as diagnostic biomarkers and treatments for diseases.

1351

Molecular subtypes-based therapies offer new potential framework for desired and precise outcome in clinical settings. Current treatment strategies in colorectal cancer are largely'one drug fit all’model for patients that display same pathological conditions. However, CRC is a veryheterogenoussetofmalignancythatdoesnotsupportforabovecriteria. Eachsubtypedisplays different pathological and genetic signatures. Based on these features, therapeutic stratification for individual patients may be designed, which may ultimately lead to improved therapeutic outcomes. In this comprehensive review, we have attempted to briefly outline major CRC pathways. A detailed overview of molecular subtypes and their clinical significance has been discussed. Present and future methods, governing CRC subtyping in the era of personalized therapy with a special emphasis on CMS subtypes of CRC has been reviewed. Together, discovery and validation of new CRC patient stratification methods, screening for novel therapeutic targets, and enhanced diagnosis of CRC may improve the treatment outcome.

1164

Osteogenesis imperfecta (OI) is mainly characterized by bone fragility and Ehlers-Danlos syndrome (EDS) by connective tissue defects. Mutations in COL1A1 or COL1A2 can lead to both syndromes. OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type I procollagen. In this study, we identified a Thai patient having OI type III, EDS, brachydactyly, and dentinogenesis imperfecta. His dentition showed delayed eruption, early exfoliation, and severe malocclusion. For the first time, ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion, bonelike dentin, loss of dentinal tubules, and reduction in hardness and elasticity, suggesting severe developmental disturbance. These severe dental defects have never been reported in OI or EDS. Exome sequencing identified a novel de novo heterozygous glycine substitution, c.3296G>A, p. Gly1099Glu, in exon 49 of COL1A2. Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage. Notably, two of these three patients did not show hyperextensible joints and hypermobile skin, while our patient at the age of 5 years had not developed intracranial hemorrhage. Here, we demonstrate that the novel glycine substitution in the carboxyl region of alpha2 (I) collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects, expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.

1229

Borna disease virus 1 (BoDV-1) is neurotropic prototype of Bornaviruses causing neurological diseases and maintaining persistent infection in brain cells of mammalian species. Long non-coding RNA (lncRNA) is transcript of more than 200 nucleotides without protein-coding function regulating various biological processes as proliferation, apoptosis, cell migration and viral infection. However, regulatory of lncRNAs in BoDV-1 infection remains unknown. To identify differential expression profiles and predict functions of lncRNA in BoDV-1 infection, microarray data showed that 3528 lncRNAs and 2661 lncRNAs were differentially expressed in Strain V and Hu-H1 BoDV-infected groups compared with control groups, respectively. Gene Ontology (GO) and pathway analysis suggested that differential lncRNAs may be involved in regulation of metabolic, biological regulation, cellular process, endocytosis, viral infections and cell adhesion processes, cancer in both BoDV-infected strains. ENSMUST00000128469 was found down-regulated in both BoDV-infected groups compared with control groups consistent with microarray (p<0.05). ceRNA analysis indicated possible interaction networks as ENSMUST00000128469/miR-22-5p, miR-206-3p, miR-302b-5p, miR-302c-3p, miR-1a-3p/Igf1. Igf1 was found up-regulated in both BoDV-infected groups compared with control groups (p<0.05). Possible functions of predicted target mRNAs and miRNAs of ENSMUST00000128469 were involved in cell proliferation, transcriptional misregulation and proteoglycan pathways enriched in cancer. lncRNA may be involved in regulation of Hu-H1 inhibited cell proliferation and promoted apoptosis through NF-κB, JNK/MAPK signaling, BCL2 and CDK6/E2F1 pathways different from Strain V. Possible interaction networks as ENSMUST00000128469/miR-22-5p, miR-206-3p, miR-302b-5p, miR-302c-3p, miR-1a-3p/Igf1 may involve in regulation of cell proliferation, apoptosis, and cancer.

1238

1178

Lysine succinylation (Ksucc), defined as a transfer of a succinyl group to a lysine residue of a protein, is a newly identified protein post-translational modification^1-3. This chemical modification is reversible, dynamic, and evolutionarily conserved⁴ where it has been comprehensively studied in both bacterial and mammalian cells^5-7. Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated^5e7. Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases, including cardiovascular diseases and cancer^7e9. Therefore, an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases. In this review, we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.

1238

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro, and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsamiR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

1219

Epithelial-mesenchymal Transition (EMT) is a de-differentiation program that imparts tumor cells with the phenotypic and cellular plasticity required for drug resistance, metastasis, and recurrence. This dynamic and reversible events is governed by a network of EMT-transcription factors (EMT-TFs) through epigenetic regulation. Many chromatin modifying-enzymes utilize metabolic intermediates as cofactors or substrates; this suggests that EMT is subjected to the metabolic regulation. Conversely, EMT rewires metabolic program to accommodate cellular changes during EMT. Here we summarize the latest findings regarding the epigenetic regulation of EMT, and discuss the mutual interactions among metabolism, epigenetic regulation, and EMT. Finally, we provide perspectives of how this interplay contributes to cellular plasticity, which may result in the clinical manifestation of tumor heterogeneity.

1245

Gastric cancer remains one of the leading causes of cancer-related death worldwide, and most of the cases are associated with Helicobacter pylori infection. This bacterium promotes the production of reactive oxygen species (ROS), which cause DNA damage in gastric epithelial cells. In this study, we evaluated the expression of important genes involved in the recognition of DNA damage (ATM, ATR, and H2AX) and ROS-induced damage repair (APE1) and the expression of some miRNAs (miR-15a, miR-21, miR-24, miR-421 and miR-605) that target genes involved in the DNA damage response (DDR) in 31 fresh tissues of gastric cancer. Cytoscape v3.1.1 was used to construct the postulated miRNA: mRNA interaction network. Analysis performed by real-time quantitative PCR exhibited significantly increased levels of the APE1 (RQ=2.55, p<0.0001) and H2AX (RQ=2.88, p=0.0002) genes beyond the miR-421 and miR-605 in the gastric cancer samples. In addition, significantly elevated levels of miR-21, miR-24 and miR-421 were observed in diffuse-type gastric cancer. Correlation analysis reinforced some of the gene: gene (ATM/ATR/H2AX) and miRNA: mRNA relationships obtained also with the interaction network. Thus, our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage, which could confer an advantage to cell survival and proliferation in the tumor microenvironment.

1245

The majority of non-melanoma skin cancer (NMSC) is cutaneous basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), which are also called keratinocyte carcinomas, as both of them originate from keratinocytes. The incidence of keratinocyte carcinomas is over 5 million per year in the US, three-fold higher than the total incidence of all other types of cancer combined. While there are several reports on gene expression profiling of BCC and SCC, there are significant variations in the reported gene expression changes in different studies. One reason is that tumor-adjacent normal skin specimens were not included in many studies as matched controls. Furthermore, while numerous studies of skin stem cells in mouse models have been reported, their relevance to human skin cancer remains unknown. In this report, we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the control. Among several novel findings, we discovered a significant number of zinc finger encoding genes up-regulated in human BCC. In BCC, a novel link was found between hedgehog signaling, Wnt signaling, and the cilium. While the SCC cancerstem-cell gene signature is shared between human and mouse SCCs, the hair follicle stem-cell signature of mice was not highly represented in human SCC. Differential gene expression (DEG) in human BCC shares gene signature with both bulge and epidermal stem cells. We have also determined that human BCCs and SCCs have distinct gene expression patterns, and some of them are not fully reflected in current mouse models.

1349

The genetic alterations associated with cell transformation are in large measure expressed in the metabolic phenotype as cancer cells proliferate and change their local environment, and prepare for metastasis. Qualitatively, the fundamental biochemistry of cancer cells is generally the same as in the untransformed cells, but the cancer cells produce a local environment, the TME, that is hostile to the stromal cells, and compete for nutrients. In order to proliferate, cells need sufficient nutrients, either those that cannot be made by the cells themselves, or must be made from simpler precursors. However, in solid tumors, the nutrient supply is often limiting given the potential for rapid proliferation, and the poor quality of the vasculature. Thus, cancer cells may employ a variety of strategies to obtain nutrients for survival, growth and metastasis. Although much has been learned using established cell lines in standard culture conditions, it is becoming clear from in vivo metabolic studies that this can also be misleading, and which nutrients are used for energy production versus building blocks for synthesis of macromolecules can vary greatly from tumor to tumor, and even within the same tumor. Here we review the operation of metabolic networks, and how recent understanding of nutrient supply in the TME and utilization are being revealed using stable isotope tracers in vivo as well as in vitro.

1267

Lev/MSNs/n-HA/PU has been proved to be a novel scaffold material to treat bone defect caused by chronic osteomyelitis. We have previously identified that this material can effectively treat chronic osteomyelitis caused by Staphylococcus aureus in vivo. However, the potential mechanisms of antibacterial and osteogenic induction properties remain unclear. Thus, for osteogenesis property, immunohistochemistry, PCR, and Western blot were performed to detect the expression of osteogenic markers. Furthermore, flow cytometry and TUNEL were applied to analyze MC3T3-E1 proliferation and apoptosis. For antibacterial property, the material was co-cultivated with bacteria, bacterial colony forming units was counted and the release time of the effective levofloxacin was assayed by agar disc-diffusion test. Moreover, scanning electron microscope was applied to observe adhesion of bacteria. In terms of osteogenic induction, we found BMSCs adherently grew more prominently on Lev/MSNs/n-HA/PU. Lev/MSNs/n-HA/PU also enhanced the expression of osteogenic markers including OCN and COL1α1, as well as effectively promoted the transition from G1 phase to G2 phase. Furthermore, Lev/MSNs/n-HA/PU could reduce apoptosis of MC3T3-E1. Besides, both Lev/MSNs/n-HA/PU and n-HA/PU materials could inhibit bacterial colonies, while Lev/MSNs/n-HA/PU possessed a stronger antibacterial activities, and lower bacterial adhesion than n-HA/PU. These results illustrated that Lev/MSNs/n-HA/PU composite scaffold possess favorable compatibility in vitro, which induce osteogenic differentiation of MSCs, promote proliferation and differentiation of MC3T3-E1, and inhibit apoptosis. Moreover, clear in vitro antibacterial effect of Lev/MSNs/n-HA/PU was also observed. In summary, this study replenishes the potential of Lev/MSNs/n-HA/PU composite scaffold possess dual functions of anti-infection and enhanced osteogenesis for future clinical application.

1123

RNA-induced silencing complex (RISC) is one of the basic eukaryotic cellular machinery which plays a pivotal role in post-transcriptional gene regulation. Discovery of miRNAs and their role in gene regulation have changed the course of modern biology. The method of gene silencing using small interfering RNAs and miRNAs has become major tool in molecular biology and genetic engineering. Hepatocellular Carcinoma (HCC) is a very common malignancy of liver in developing countries and due to various risk factors; the prevalence of this disease is rapidly increasing throughout the globe. There exists an imbalance in interplay between oncogenes and tumor suppressor genes and their regulation plays a major role in HCC growth, development and metastasis. The regulatory function of RISC and miRNAs make them a very important mediators of cancer signaling in HCC. Therefore, targeting the RISC complex for HCC therapy is the need of the time.

1182

Colorectal cancer is a leading cause of cancer deaths. Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies. Here, we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin treatment. Integrated transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene expression. CRISPR/Cas9 silencing of fibroblast growth factor receptor 1 (FGFR1) and oxytocin receptor (OXTR) helped overcome oxaliplatin resistance. Similarly, treatment with oxaliplatin in combination with an FGFR1 inhibitor (PD166866) or an antagonist of OXTR (L-368, 899) suppressed chemoresistant organoids. However, oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid, suggesting that chromatin accessibility changes are patient-specific. The use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.

1153

The breast cancer is one of the most common cancer affecting millions of lives worldwide. Though the prevalence of breast cancer is worldwide; however, the developing nations are having a comparatively higher percentage of breast cancer cases and associated complications. The molecular etiology behind breast cancer is complex and involves several regulatory molecules and their downstream signaling. Studies have demonstrated that the CD44 remains one of the major molecule associated not only in breast cancer but also several other kinds of tumors. The complex structure and functioning of CD44 posed a challenge to develop and deliver precise anti-cancerous drugs against targeted tissue. There are more than 20 isoforms of CD44 reported till date associated with several kinds of tumor in the using breast cancer. The success of any anti-cancerous therapy largely depends on the precise drug delivery system, and in modern days nanotechnology-based drug delivery vehicles are the first choice not only for cancer but several other chronic diseases as well. The Carbon nanotubes (CNTs) have shown tremendous scope in delivering the drug by targeting a particular receptor and molecules. Functionalized CNTs including both SWCNTs and MWCNTs are a pioneer in drug delivery with higher efficacy. The present work emphasized mainly on the potential of CNTs including both SWCNTs and MWCNTs in drug delivery for anti-cancerous therapy. The review provides a comprehensive overview of the development of various CNTs and their validation for effective drug delivery. The work focus on drug delivery approaches for breast cancer, precisely targeting CD44 molecule.

1256

Diversity analysis and taxonomic profiles can be generated from marker-gene sequence data with the help of many available computational tools. The Quantitative Insights into Microbial Ecology Version 2 (QIIME2) has been widely used for 16S rRNA data analysis. While many articles have demonstrated the use of QIIME2 with suitable datasets, the application to preclinical data has rarely been talked about. The issues involved in the pre-clinical data include the low-quality score and small sample size that should be addressed properly during analysis. In addition, there are few articles that discuss the detailed statistical methods behind those alpha and beta diversity significance tests that researchers are eager to find. Running the program without knowing the logic behind it is extremely risky. In this article, we first provide a guideline for analyzing 16S rRNA data using QIIME2. Then we will talk about issues in pre-clinical data, and how they could impact the outcome. Finally, we provide brief explanations of statistical methods such as group significance tests and sample size calculation.

1158

Prostate cancer (PCa) metastasis is considered the leading cause of cancer death in males. Therapeutic strategies and diagnosis for stage-specific PCa have not been well understood. Rho guanine nucleotide exchange factor 38 (ARHGEF38) is related to tumor cell polarization and is frequently expressed in PCa. Microarray data of PCa were downloaded from GEO and TCGA databases. A total of 243 DEGs were screened, of which, 32 genes were upregulated. The results of enrichment analysis showed the participation of these DEGs in the tumor cell metastasis pathway. ARHGEF38 was significantly up-regulated in the four most prevalent cancers worldwide (p<0.05), and its expression was higher in the tumor samples with higher Gleason score (GS). IHC, qRT-PCR, and western-blot analyses showed the higher expression of ARHGEF38 in PCa than benign prostatic hyperplasia (BPH). In addition, IHC results demonstrated a higher expression of ARHGEF38 in high-grade PCa than the low-grade PCa.

1139

The incidence of haemoglobinopathy is high in China, especially south of the Yangtze River. However, the exact status of haemoglobinopathy in Sichuan is unknown. To carry out a detailed research of haemoglobinopathy in individuals living in Sichuan, 13, 298 subjects without clinical symptoms who were living in Sichuan Province, with an age distribution of 5-73 years, were included in this study. Between March 2014 and July 2017, these subjects received examinations at the Medical Lab of Chengdu Women's & Children's Central Hospital. Mean corpuscular volume (MCV) <82 fL or mean corpuscular haemoglobin (MCH) <27 pg was used to indicate haemoglobinopathy carriers. Abnormal haemoglobin was screened by electrophoresis, and genes were sequenced to identify genotypes. Genotype diagnosis of alpha-and beta-thalassaemia was carried out by using PCR and shunt hybridization. There were 638 suspected haemoglobinopathy carriers (4.80%, 638/13, 298). DNA sequencing identified 6 subjects with abnormal haemoglobin genotypes and 15 subjects with Hb E. The frequency of heterozygosity for thalassaemia was 4.12% (1.48% for α-thalassaemia and 2.61% for β-thalassaemia) in Sichuan Province. The mutation spectrum of α-thalassaemia consisted of the five most common mutations: –^SEA, -α^3.7, -α^4.2, α^CS, and α^QS. Seven types of β-thalassaemia mutation were found in this study: CD41-42 (-TTCT) was the most frequent (28.47%), followed by 17 (A>T), -28 (A>G), and IVS-II-654 (C>T). The main abnormal haemoglobin genotype (HbE) and thalassaemia genotype (–^SEA, CD41-42 (-TTCT)) were consistent with those in other regions of China, but the carrier rate of β-thalassaemia in Sichuan was higher than that of α-thalassaemia.

1137

Extracellular vesicles (EVs) such as microvesicles (MIVs) play an important role in intercellular communications. MIVs are small membrane vesicles sized 100-1000 nm in diameter that are released by many types of cells, such as mesenchymal stem cells (MSCs), tumor cells and adipose-derived stem cells (ADSC). As EVs can carry out autocrine and paracrine functions by controlling multiple cell processes, it is conceivable that EVs can be used as delivery vehicles for treating several clinical conditions, such as to improve cardiac angiogenesis after myocardial infarction (MI). Here, we seek to investigate whether ADSC-derived MIVs contain microRNAs that regulate angiogenesis and affect cell migration of endothelial cells. We first characterized the ADSC-derived MIVs and found that the MIVs had a size range of 100 e300 nm, and expressed the MIV marker protein Alix. We then analyzed the microRNAs in ADSCs and ADSC-derived MIVs and demonstrated that ADSC-derived MIVs selectively released a panel of microRNAs, several of which were related to angiogenesis, including two members of the let-7 family. Furthermore, we demonstrated that ADSC-derived MIVs promoted the cell migration and invasion of the HUVEC endothelial cells. The PKH26-labeled ADSC-derived MIVs were effectively uptaken into the cytoplasm of HUVEC cells. Collectively, our results demonstrate that the ADSC-derived MIVs can promote migration and invasion abilities of endothelial cells, suggesting pro-angiogenetic potential. Future studies should focus on investigating the roles and mechanisms through which ADSC-derived MIVs regulate angiogenesis.

1202

Bone morphogenetic protein 9 (BMP9) (or GDF2) was originally identified from fetal mouse liver cDNA libraries. Emerging evidence indicates BMP9 exerts diverse and pleiotropic functions during postnatal development and in maintaining tissue homeostasis. However, the expression landscape of BMP9 signaling during development and/or in adult tissues remains to be analyzed. Here, we conducted a comprehensive analysis of the expression landscape of BMP9 and its signaling mediators in postnatal mice. By analyzing mouse ENCODE transcriptome datasets we found Bmp9 was highly expressed in the liver and detectable in embryonic brain, adult lungs and adult placenta. We next conducted a comprehensive qPCR analysis of RNAs isolated from major mouse tissues/organs at various ages. We found that Bmp9 was highly expressed in the liver and lung tissues of young adult mice, but decreased in older mice. Interestingly, Bmp9 was only expressed at low to modest levels in developing bones. BMP9-associated TGFβ/BMPR type I receptor Alk1 was highly expressed in the adult lungs. Furthermore, the feedback inhibitor Smads Smad6 and Smad7 were widely expressed in mouse postnatal tissues. However, the BMP signaling antagonist noggin was highly expressed in fat and heart in the older age groups, as well as in kidney, liver and lungs in a biphasic fashion. Thus, our findings indicate that the circulating BMP9 produced in liver and lungs may account for its pleiotropic effects on postnatal tissues/organs although possible roles of BMP9 signaling in liver and lungs remain to be fully understood.

1316

Propofol is widely used as an intravenous drug for induction and maintenance in general anesthesia. Hypoxemia is a common complication during perianesthesia. We want to know the effect of propofol on spatial memory and LTP (Long-term potentiation) under hypoxic conditions. In this study, 84 seven-day-old SpragueeDawley rats were randomly assigned into six groups (n=14) -four control groups: lipid emulsion solvent + 50% oxygen (CO), lipid emulsion solvent + room air (CA), lipid emulsion solvent + 18% oxygen (CH), and propofol + 50% oxygen (propofoleoxygen, PO); and two experiment groups: propofol + room air (propofol eair, PA), and propofol + 18% oxygen (propofolehypoxia, PH). After receiving propofol (50 mg/kg) or the same volume of intralipid intraperitoneal (5.0 ml/kg), injected once per day for seven consecutive days, the rats were exposed to 18% oxygen, 50% oxygen and air, until recovery of the righting reflex. We found that the apoptotic index and activated caspase-3 increased in the PH group (P<0.05) compared with the PA group, fEPSP (field excitatory postsynaptic) potential and success induction rate of LTP reduced in all propofol groups (P<0.05). Compared with the PO group, the fEPSP and success induction rate of LTP reduced significantly in the PA and PH groups (P<0.05). Moreover, compared with CH group, the average time of escape latency was longer, and the number of platform location crossings was significantly reduced in the PH group (P<0.05). Thus, we believe that adequate oxygen is very important during propofol anesthesia.

1111

Traumatic brain injury (TBI) is the major cause of high mortality and disability rates worldwide. Pioglitazone is an activator of peroxisome proliferator-activated receptor-gamma (PPARγ) that can reduce inflammation following TBI. Clinically, neuroinflammation after TBI lacks effective treatment. Although there are many studies on PPARγ in TBI animals, only few could be converted into clinical, since TBI mechanisms in humans and animals are not completely consistent. The present study, provided a potential theoretical basis and therapeutic target for neuroinflammation treatment after TBI. First, we detected interleukin-6 (IL-6), nitric oxide (NO) and Caspase-3 in TBI clinical specimens, con firming a presence of a high expression of inflammatory factors. Western blot (WB), quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were used to detect PPARγ, IL-6, and p-NF-κB to identify the mechanisms of neuroinflammation. Then, in the rat TBI model, neurobehavioral and cerebral edema levels were investigated after intervention with pioglitazone (PPARγ activator) or T0070907 (PPARγ inhibitor), and PPARγ, IL-6 and p-NF-κB were detected again by qRT-PCR, WB and immunofluorescence (IF). The obtained results revealed that:1) increased expression of IL-6, NO and Caspase-3 in serum and cerebrospinal fluid in patients after TBI, and decreased PPARγ in brain tissue;2) pioglitazone could improve neurobehavioral and reduce brain edema in rats after TBI;3) the protective effect of pioglitazone was achieved by activating PPARγ and reducing NF-κB and IL-6. The neuroprotective effect of pioglitazone on TBI was mediated through the PPARγ/NF-κB/IL-6 pathway.

1162

Transcervical resection of adhesion (TCRA) is the standard treatment for the intrauterine adhesions, but the recurrence of adhesions is a tough problem for the gynecologist. In addition, the therapeutic strategy after TCRA about prevention of recurrence remains controversial especially for the patients with moderate to severe intrauterine adhesions (IUAs). Hence, we designed this study to explore the safety and efficacy of fresh amnion grafts for preventing the recurrence after TCRA for patients with moderate to severe IUAs. One hundred patients with moderate to severe IUAs who presented with a history of hypomenorrhea, amenorrhea and infertility were included in the study from January 2015 to December 2017. Patients were divided into amnion group (52 patients) and chitosan group (48 patients). Fresh amnion grafts or intrauterine injections of chitosan were administered after TCRA. Transvaginal ultrasonography (TVUS) and hysteroscopy were performed at the first and third month after the operation. The surgical procedures for all patients were completed successfully without relevant complications. In amnion group, 8 patients exhibited relapse in the first month and 2 patients in three months after surgery; in chitosan group, 23 women exhibited relapse in the first month and 18 patients in three months after surgery. Statistical analysis revealed that the recurrence rate of adhesion in amnion group was significantly lower than those of chitosan group in the first and three months after surgery (P₁=0.000, P₂=0.000). After TCRA, fresh amnion graft plays a significant role in preventing further adhesions than injections of chitosan.

1152

A decrease in microbial infection in adolescents is implicated with an increase in the incidence of asthma and allergic diseases in adulthood, indicating that the microbiome plays a critical role in asthma. However, the microbial composition of the lower respiratory tract remains unclear, hindering the further exploration of the pathogenesis of asthma. This study aims to explore the microbial distribution and composition in the lungs of normal rats and rats with allergic asthma via 16S rDNA sequencing.The DNA of the pulmonary microbiome was extracted from the left lungs collected from normal control group (NC), saline control group (SC), and allergic asthma group (AA) under aseptic conditions. After the 16s rDNA V4eV5 region was amplified, the products were sequenced using Illumina high-throughput technology and subjected to operational taxonomic unit (OTU) cluster and taxonomy analysis.The OTU values of AA increased significantly compared with those of NC and SC. Microbiome structure analysis showed that the dominant phylum of the pulmonary microbiome changed from Proteobacteria in NC to Firmicutes in AA. Linear discriminant analysis indicated that the key microbiomes involved in the three groups varied.Numerous microbiomes stably settled in the lungs of the rats in NC and AA. The structure and diversity of the pulmonary microbiome in AA differed from those in NC.

1146

Natural killer (NK) cells are thought to play a key role in the successful establishment of a pregnancy by facilitating immunological adaptation of the semi-allogeneic developing embryo. The aim of this study was to explore the cell number, immunophenotypic characteristics, and activities of peripheral blood NK cells in women with repeated implantation failure (RIF). Peripheral blood was obtained from 27 women with RIF and 11 healthy, fertile controls during the middle luteal phase of the menstrual cycle. CD3^-CD56⁺NK cells were quantified and analyzed by flow cytometry for the expression of cytolytic molecules (granzyme B, granulysin, and perforin) as well as cell surface receptors responsible for NK cell activation or inhibition (NKG2D, NKp30, NKp46, CD158a, CD158b). NK cytotoxicity was measured at three effector-to-target cell ratios. Women with RIF and fertile controls did not differ significantly in the percentage of circulating CD3^-CD56⁺NK cells, or in the proportions of these cells that expressed granzyme B, granulysin, or perforin. The two groups also did not differ significantly in the proportions of NK cells expressing the receptors NKG2D, NKp30, NKp46, CD158a or CD158b. General linear model analysis showed that NK cytotoxicity increased with effector-to-target cell ratio. However, NK cytotoxicity did not differ significantly between patients with RIF and fertile controls. These results suggest that RIF is not associated with significant alterations in the number or function of peripheral blood NK cells.

1188