Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.

PURPOSE: High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances. METHODS: Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA). RESULTS: In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results. CONCLUSION: The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.

Macrophages in spinal cord injury: phenotypic and functional change from exposure to myelin debris.

Macrophage activation and persistent inflammation contribute to the pathological process of spinal cord injury (SCI). It was reported that M2 macrophages were induced at 3-7 days after SCI but M2 markers were reduced or eliminated after 1 week. By contrast, M1 macrophage response is rapidly induced and then maintained at injured spinal cord. However, factors that modulate macrophage phenotype and function are poorly understood. We developed a model to distinguish bone-marrow derived macrophages (BMDMs) from residential microglia and explored how BMDMs change their phenotype and functions in response to the lesion-related factors in injured spinal cord. Infiltrating BMDMs expressing higher Mac-2 and lower CX3CR1 migrate to the epicenter of injury, while microglia expressing lower Mac-2 but higher CX3CR1 distribute to the edges of lesion. Myelin debris at the lesion site switches BMDMs from M2 phenotype towards M1-like phenotype. Myelin debris activates ATP-binding cassette transporter A1 (ABCA1) for cholesterol efflux in response to myelin debris loading in vitro. However, this homeostatic mechanism in injured site is overwhelmed, leading to the development of foamy macrophages and lipid plaque in the lesion site. The persistence of these cells indicates a pro-inflammatory environment, associated with enhanced neurotoxicity and impaired wound healing. These foamy macrophages have poor capacity to phagocytose apoptotic neutrophils resulting in uningested neutrophils releasing their toxic contents and further tissue damage. In conclusion, these data demonstrate for the first time that myelin debris generated in injured spinal cord modulates macrophage activation. Lipid accumulation following macrophage phenotype switch contributes to SCI pathology.

An open air research study of blast-induced traumatic brain injury to goats.

PURPOSE: We once reported blast-induced traumatic brain injury (bTBI) in confined space. Here, bTBI was studied again on goats in the open air using 3.0 kg trinitrotoluene. METHODS: The goats were placed at 2, 4, 6 and 8 m far from explosion center. Trinitrotoluene (TNT) was used as the source of the blast wave and the pressure at each distance was recorded. The systemic physiology, electroencephalogram, serum level of S-100 beta, and neuron specific enolase (NSE) were determined pre and post the exposure. Neuroanatomy and neuropathology were observed 4 h after the exposure. RESULTS: Simple blast waveforms were recorded with parameters of 702.8 kPa-0.442 ms, 148.4 kPa-2.503 ms, 73.9 kPa-3.233 ms, and 41.9 kPa-5.898 ms at 2, 4, 6 and 8 m respectively. Encephalic blast overpressure was on the first time recorded in the literature by us at 104.2 kPa-0.60 ms at 2 m, where mortality and burn rate were 44% and 44%. Gross examination showed that bTBI was mainly manifested as congestive expansion of blood vessels and subarachnoid hemorrhage, which had a total incidence of 25% and 19% in 36 goats. Microscopical observation found that the main pathohistological changes were enlarged perivascular space (21/36, 58%), small hemorrhages (9/36, 25%), vascular dilatation and congestion (8/36, 22%), and less subarachnoid hemorrhage (2/36, 6%). After explosion, serum levels of S-100b and NSE were elevated, and EEG changed into slow frequency with declined amplitude. The results indicated that severity and incidence of bTBI is related to the intensity of blast overpressure. CONCLUSION: Blast wave can pass through the skull to directly injure brain tissue.

Morphological study of Schwann cells remyelination in contused spinal cord of rats.

OBJECTIVE: To study the role and effect of Schwann cells (SCs) remyelination in contused spinal cord. METHODS: Green fluorescence protein expressing-SCs were transplanted into the epicenter, rostral and caudal tissues of the injury site at 1 week after the spinal cords were contused. At 6 weeks, the spinal cords were removed for cryosections, semithin sections and ultrathin sections, and then immunocytochemical staining of myelin basic protein (MBP), P0 protein (P0) and S100 protein (S100) was carried out on the cryosections. Qualitative and semiquantitative analyses were performed on the cryosections and semithin sections. Ultrastructure of myelinated fibers was observed on the ultrathin sections under electron microscope. RESULTS: Transplanted SCs and myelinated fibers immunocytochemically labeled by MBP, P0 as well as S100 distributed in whole injured area. The quantity of myelinated fibers labeled by the three myelin proteins showed no statistical difference, however, which was significantly larger than that of controls. On the semithin sections, the experimental group demonstrated more myelinated fibers in the injured area than the controls, but the fibers had smaller diameter and thinner myelin sheath under electron microscope. CONCLUSION: SCs can promote regeneration of injured nerve fibers and enhance remyelination, which may be histological basis of SCs-mediated functional repair of injured spinal cords.

Mixed l1/l- fault detection observer design for delayed 2D positive systems in FM LSS Models.

This study is concerned with the problem of the mixed l1/l- fault detection (FD) observer for delayed two-dimensional (2D) positive systems (PSs). The necessary and sufficient conditions (NSCs) are derived under which the residual error system is asymptotically stable (AS) and has the prescribed performance level. The conservatism is greatly reduced compared to the existing results. A new performance analysis method and the mixed l1/l- FD observer design are presented. Firstly, the calculation of l1/l- index for delayed 2D PSs is proposed by establishing the equivalence between the delayed system and the higher dimensional delay-free system in sense of l1 and l- indexes. Secondly, NSCs are developed such that the delayed 2D PS is AS with a desired mixed l1/l- performance. Thirdly, the sufficient conditions of the observer design are further developed based on linear programming. An iterative algorithm is formulated to minimize and maximize the impact of system disturbances and faults on the output signal, respectively. Finally, we present two examples to verify the superiority of the obtained results.

Nanoscale Porphyrin Metal-Organic Frameworks Deliver siRNA for Alleviating Early Pulmonary Fibrosis in Acute Lung Injury.

Acute lung injury (ALI) has high mortality and still lacks novel and efficient therapies. Zinc finger E-box binding homeobox 1 and 2 (ZEB1/2) are highly expressed in the early stage of ALI and are positively correlated with the progression of pulmonary fibrosis. Herein, we developed a nanoscale Zr(IV)-based porphyrin metal-organic (ZPM) framework to deliver small interfering ZEB1/2 (siZEB1/2) to alleviate early pulmonary fibrosis during ALI. This pH-responsive nano-ZPM system could effectively protect siRNAs during lung delivery until after internalization and rapidly trigger siRNA release under the mildly acidic environment of the endo/lysosome (pH 4.0-6.5) for transfection and gene silencing. Furthermore, the in vivo studies confirmed that this nano-ZPM system could anchor in inflamed lungs. Moreover, the ZEB1/2 silencing led to increased E-cadherin and decreased α-SMA levels. Overall, the nano-ZPM system was an excellent non-viral vector system to deliver siRNAs to alleviate early pulmonary fibrosis during ALI.

Global analysis of the COVID-19 research landscape and scientific impact.

OBJECTIVES: To consider a 1-year time window of the coronavirus disease 2019 (COVID-19) crisis to integrate qualitative and quantitative data and provide an in-depth analysis of all COVID-19 publications from geographical, epidemiological and chronological perspectives. METHODS: Publications on COVID-19 from December 1, 2019, to December 31, 2020 without document type limitations were extracted from the Web of Science database. Microsoft Excel 2016, GraphPad Prism 9, VOSviewer 1.6.15 and IBM SPSS 21.0 were used to analyze the global epidemiological publication landscape and its correlations, research hotspots around the world and the top 5 countries in terms of publications. RESULTS: A total of 51,317 documents were analyzed in the present study. The publication trend could be divided into an increasing output stage and an explosive output stage. There were positive correlations between monthly publications, confirmed cases and deaths. Research hotspots from the whole year, from individual quarters, and from the top 5 countries with the most publications were further identified. CONCLUSIONS: The correlation analysis of publications indicated that confirmed cases and deaths were forces driving the scientific output, reflecting the growing trend to some extent. Moreover, the hotspot analysis provided valuable information for scientists, funders, policy and decision-makers to determine what areas should be their focus when faced with public health emergencies in the future.

The Montreal platelet syndrome kindred has type 2B von Willebrand disease with the VWF V1316M mutation.

Montreal platelet syndrome (MPS), hitherto described in only one kindred, is a hereditary thrombocytopenia associated with mucocutaneous bleeding, giant platelets, and spontaneous platelet aggregation in vitro. These are features shared with some forms of type 2B von Willebrand disease (VWD); however, the MPS kindred had not been investigated for VWD. We found that all affected MPS family members had borderline to normal von Willebrand factor antigen (VWF:Ag; 0.43-0.75 U/mL), discrepantly low ristocetin cofactor activity (VWF:RCo; 0.16-0.29 U/mL), and normal factor VIII coagulant activity (FVIII:C; 0.57-1.04 U/mL). Unaffected family members all had normal VWF:Ag, VWF:RCo, and FVIII:C levels. In addition, persons with MPS, but not unaffected family members, had loss of plasma (but not platelet) high molecular weight VWF multimers, and were heterozygous for the previously reported V1316M type 2B VWD mutation. Thus, in reevaluating this kindred, we determined that patients with MPS have type 2B VWD with the V1316M VWF mutation.

Tumor necrosis factor alpha gene polymorphism is associated with the outcome of trauma patients in Chinese Han population.

BACKGROUND: Tumor necrosis factor (TNF) is a proinflammatory cytokine that plays a major role in the sepsis and multiple organ dysfunction secondary to major trauma. The purpose of this article was to research the clinical relevance of the TNF gene polymorphism in patients with major trauma. METHODS: Three hundred six patients with major trauma were prospectively recruited. The TNF gene polymorphisms were genotyped using restriction fragment length polymorphism analysis. Plasma TNF-α levels were determined with enzyme-linked immunosorbent assay. Sepsis morbidity rate and multiple organ dysfunction scores were accessed. RESULTS: The TNF-α/-308 polymorphism was shown to be well associated with increased capacity of peripheral leukocytes to produce TNF-α in response to ex vivo lipopolysaccharide stimulation in trauma patients at admission. Results from association study indicated that trauma patients carrying the TNF-α/-308/A allele were more likely complicated with sepsis. CONCLUSIONS: The TNF-α/-308 polymorphism might be used as a biomarker for the assessment of outcome of trauma patients, but the TNF-ß/252 gene polymorphism might not influence the development of complications in patients with major trauma.

Functional significance of the Toll-like receptor 4 promoter gene polymorphisms in the Chinese Han population.

OBJECTIVE: Toll-like receptor 4 is an important signaling receptor for lipopolysaccharide in mammals, and the variation of the promoter may affect the activity of toll-like receptor 4 expression. Although 12 single nucleotide polymorphisms have been identified in the toll-like receptor 4 promoter, little is known about the functional significance of these single nucleotide polymorphisms. DESIGN: Genetic functional and association studies. SETTING: National Key Laboratory of Trauma and Departments of Traumatic Surgery in two teaching hospitals. SUBJECTS: Three hundred seventy-nine healthy volunteers and 303 patients with major trauma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five single nucleotide polymorphisms identified in the toll-like receptor 4 promoter in the Chinese Han population were selected. Three of them revealed a close relationship with transcription factor binding sites. Among the three single nucleotide polymorphisms, only the T-2242C polymorphism significantly increased transcriptional activities of the toll-like receptor 4 promoter, as shown by reporter gene assay. Results from flow cytometry and ex vivo responsiveness of peripheral blood leukocytes indicated that the T-2242C polymorphism was well-associated with increased expression of toll-like receptor 4 protein and production of tumor necrosis factor-alpha. The clinical relevance of these single nucleotide polymorphisms was then investigated in 303 patients with major trauma. The peripheral blood leukocytes of trauma patients with the variant C allele revealed greater capacity to produce tumor necrosis factor-alpha and interleukin-6 on the admission day. Furthermore, the toll-like receptor 4/2242 polymorphism was significantly associated with higher sepsis morbidity rates and multiple organ dysfunction scores in patients with major trauma. CONCLUSIONS: The toll-like receptor 4/2242 polymorphism is a functional variant and might be used as a relevant risk estimate for organ dysfunction and sepsis in trauma patients.

The effects of the M2a macrophage-induced axonal regeneration of neurons by arginase 1.

BACKGROUND: Spinal cord injury (SCI) is a challenge worldwide, but there are no effective treatments or therapeutic methods in the clinic. Recent studies have shown that type I arginase (Arginase1, Arg1) is closely associated with the treatment of SCI. The classical treatment for SCI involves filling the local area of SCI with activated M2a macrophages to allow the repair and regeneration of some synapses, but the specific mechanism of action of Arg1 is not clear. METHOD: In the present study, we first induced the polarization of RAW264.7 macrophages to M2a-type cells using IL-4 and constructed an Arg1 knockout cell line through the use of shRNA; we used these cells to treat a rat model of SCI. Finally, the present study explored the mechanism and pathway by which Arginase 1 regulates spinal repair by immunoblotting and immunohistochemistry. RESULT: Suspended M2a (Arg1-/+) macrophages were transplanted into the injury site in a rat model of contusion SCI. Compared with the model group and the shArg1 group, the shScramble (shSc) group exhibited higher Basso, Beattie, Bresnahan motor function scores, more compact structures and more Nissl bodies. Immunohistochemical results showed that the shSc group expressed higher levels of NeuN (a neuronal marker) and tau (an axonal marker), as well as the up-regulation of Cdc42, N-WASP, Arp2/3 and tau, as determined by Western blot. CONCLUSION: The study found that the polarization of M2a macrophages promoted the expression of Arginase 1, which restored axonal regeneration, promoted axonal regeneration, and promoted the structural and functional recovery of the contused spinal cord.

Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial-mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-ß1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-ß1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-ß1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.

Fault detection observer design for 2-D continuous nonlinear systems with finite frequency specifications.

This research studies the problem of fault detection observer design for two-dimensional (2-D) continuous-time nonlinear systems in Takagi-Sugeno (T-S) form. Finite frequency (FF) specifications are used to design the observers, which makes observer designing different from previously proposed 2-D detection observers. Faults and disturbances are considered to be dominated in two different FF domain intervals. Fault sensitivity and disturbance robustness are measured by two FF performance indices, respectively. The aim of this paper is to design fault detection observers such that the residual error system has the sensitivity to faults and the desired robustness to disturbances. Sufficient conditions for the existence of a desired fault detection fuzzy observer are established in terms of linear matrix inequalities (LMIs). Simulation results indicate that faults can be detected effectively using the proposed method.

Functional tag SNPs inside the DRD2 gene as a genetic risk factor for major depressive disorder in the Chinese Han population.

BACKGROUND: The D2 dopamine receptor (DRD2) has been extensively investigated and has been associated with the occurrence of neuropsychiatric disorders. Polymorphisms in the DRD2 gene have also been determined as a possible predisposing component for major depressive disorders (MDD). The present study focused on evaluating the connection of polymorphisms inside the whole DRD2 gene in MDD patients as well as in non-MDD participants in a group selected from the Chinese Han population. MATERIALS AND METHODS: In total, 831 unrelated Chinese adults from the Han population were sampled, including 497 non-MDD participants and 334 MDD patients for this evaluation. After the haplotype bins were built, 14 tag single-nucleotide polymorphisms (tSNPs) and the two most investigated SNP were chosen for the whole DRD2 gene. An improved multiplex ligation detection reaction (iMLDR) technique was used to choose the genotypes. Following this, the allelic frequencies and clinical features were contrasted between the two independent Chinese Han populations. Transcriptional enhancer activities were measured to assess the functionality of the rs7131056 polymorphism. RESULTS: Sixteen SNPs were identified, including the two most examined in the Chinese Han population, and all were recurrent SNPs. Of the 16 SNPs, two (rs4648317 and rs7131056) were significantly connected to MDD. Patients with MDD were more apt to carry the rs4648317G and rs7131056A allele in contrast to the non-MDD controls (P < 0.05). The genetic risk effect on MDD occurrence was associated with the haplotype GTGATCGCGCAGGC of fourteen tag SNPs (OR = 1.52, 95% CI: 1.06 to 2.18, P = 0.02). Moreover, the rs7131056 polymorphism contained intronic silencer activities. CONCLUSIONS: This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD.

Bleomycin-enhanced alternative splicing of fibroblast growth factor receptor 2 induces epithelial to mesenchymal transition in lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an important public health problem, and it has few treatment options given its poorly understood etiology; however, epithelial to mesenchymal transition (EMT) of pneumocytes has been implicated as a factor. Herein, we aimed to explore the underlying mechanisms of lung fibrosis mediated by EMT, with a focus on the alternative splicing of fibroblast growth factor receptor 2 (FGFR2), using bleomycin (BLM)-induced lung fibrotic and transgenic mouse models. We employed BLM-induced and surfactant protein C (SPC)-Cre and LacZ double transgenic mouse models. The results showed that EMT occurred during lung fibrosis. BLM inhibited the expression of epithelial splicing regulatory protein 1 (ESRP1), resulting in enhanced alternative splicing of FGFR2 to the mesenchymal isoform IIIc. BLM-induced lung fibrosis was also associated with the activation of TGF-ß/Smad signaling. These findings have implications for rationally targetted strategies to therapeutically address IPF.

Functional significance of the TLR4/11367 polymorphism identified in Chinese Han population.

Toll-like receptor 4 (TLR4) is the central signaling receptor for lipopolysaccharide (LPS) in mammals. This study was designed to investigate the functional significance of the G11367C polymorphism, which is a novel variant we identified in the 3' untranslated region of TLR4 gene in Chinese Han population. Three hundred seventy healthy volunteers were selected. The TLR4/11367 polymorphism was genotyped using single-tube bidirectional allele-specific amplification method. The TLR4 protein expression on peripheral leukocytes and plasma tumor necrosis factor alpha levels were determined by means of flow cytometry and enzyme-linked immunosorbent assay. The post-transcriptional effect of the 11367 polymorphism was evaluated by means of reporter gene assay and real-time quantitative polymerase chain reaction. The G11367C polymorphism is a common allele in Chinese Han population, with minor allele frequency of 14.7%. In response to ex vivo LPS stimulation, the TLR4 expression on the surface of peripheral leukocytes and the plasma tumor necrosis factor alpha levels were significantly lower in carriers of 11367C variant allele than in carriers of 11367G allele. This association was allele dose dependent. We also found that the activity and the mRNA expression of luciferase was significantly smaller in human embryonic kidney 293 cells transfected with construct containing 11367C allele than in those transfected with construct containing 11367G allele. Together, these results suggest that the TLR4/11367 polymorphism may be a functional single nucleotide polymorphism, which could attenuate the LPS-induced transmembrane signaling through the alteration of post-transcriptional regulation of 3' untranslated region and target gene expression.

The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats.

Inflammatory response following spinal cord injury (SCI) is important in regulation of the repair process. Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are important donor cells for repairing SCI in different animal models. However, synergistic or complementary effects of co-transplantation of both cells for this purpose have not been extensively investigated. In the present study, we investigated the effects of co-transplantation of OECs and SCs on expression of pro- or anti-inflammatory factor and polarization of macrophages in the injured spinal cord of rats. Mixed cell suspensions containing OECs and SCs were transplanted into the injured site at 7 days after contusion at the vertebral T10 level. Compared with the DMEM, SC, or OEC group, the co-transplantation group had a more extensive distribution of the grafted cells and significantly reduced number of astrocytes, microglia/macrophage infiltration, and expression of chemokines (CCL2 and CCL3) at the injured site. The co-transplantation group also significantly increased arginase+/CD206+ macrophages (IL-4) and decreased iNOS+/CD16/32+ macrophages (IFN-γ), which was followed by higher IL-10 and IL-13 and lower IL-6 and TNF-α in their expression levels, a smaller cystic cavity area, and improved motor functions. These results indicate that OEC and SC co-transplantation could promote the shift of the macrophage phenotype from M(IFN-γ) to M(IL-4), reduce inflammatory cell infiltration in the injured site, and regulate inflammatory factors and chemokine expression, which provide a better immune environment for SCI repair.

Bleomycin (BLM) Induces Epithelial-to-Mesenchymal Transition in Cultured A549 Cells via the TGF-ß/Smad Signaling Pathway.

The epithelial-to-mesenchymal transition (EMT) is a crucial cellular event in wound healing, tissue repair, and cancer progression in adult tissues, with the interactions with numerous signals. In this study, we aimed to determine whether bleomycin (BLM), an agent that causes pulmonary fibrosis, induces the EMT of the alveolar epithelial cell line A549 and investigated the possible mechanisms. We examined the EMT involved changes in cell morphology, isoform switching of the fibroblast growth factor receptor 2 (FGFR2) by alternative splicing, and expression of the phenotypic markers including E-cadherin, vimentin, and α-SMA using RT-PCR, Western blotting, and immunofluorescence assays. A TGF-ß/Smad inhibitor was used to determine whether coculture with BLM would inhibit the EMT of A549 cells. The results showed that BLM induced the EMT of A549 cells possibly via the TGF-ß/Smad signaling pathway, evident from the decrease in the expression of E-cadherin and increase in the expression on vimentin.

Assessment of functional tag single nucleotide polymorphisms within the DRD2 gene as risk factors for post-traumatic stress disorder in the Han Chinese population.

BACKGROUND: Gene variations related to the dopaminergic pathway have been implicated in a number of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). Dopamine D2 receptor (DRD2) has been shown to significantly contribute to neuropsychiatric disorders and may specifically contribute to predisposition to PTSD. This study aimed to evaluate the association of polymorphisms within the entire DRD2 gene with PTSD in a case-control study. MATERIALS AND METHODS: A total of 834 unrelated Han Chinese adults, including 497 healthy volunteers and 337 patients with PTSD, were used in this study. Fifteen tag single-nucleotide polymorphisms (tSNPs) were selected spanning the entire DRD2 gene through the construction of haplotype bins. Genotypes were gathered using an improved multiplex ligation detection reaction (iMLDR) technique. Allelic frequencies and clinical characteristics were compared in two independent Han Chinese populations. Moreover, the functionality of the rs2075652 and rs7131056 polymorphisms were assessed by measuring transcriptional enhancer activities. RESULTS: Fifteen tag SNPs were identified in the Han Chinese population and all were common SNPs. Among 15 tSNPs, two of them (rs2075652 and rs7131056) significantly associated with PTSD. PTSD individuals were more likely to carry the rs2075652A and rs7131056A allele compared to the controls (P<0.05). The haplotype GTGATCGCGCAGGCG, had a risk effect on PTSD occurrence (OR=1.75, 95% CI: 1.24-2.48, P=0.002). Additionally, the rs2075652 polymorphism contained intronic enhancer activities. CONCLUSIONS: The rs2075652 and rs7131056 polymorphisms, and the haplotype GTGATCGCGCAGGCG within the DRD2 gene, may be potential markers to predict susceptibility to PTSD.

Synergic effects of EPI-NCSCs and OECs on the donor cells migration, the expression of neurotrophic factors, and locomotor recovery of contused spinal cord of rats.

Cell-based therapy is a promising strategy for the repair of spinal cord injury (SCI), and the synergic effects of donor cells are emphasized in recent years. In this study, epidermal neural crest stem cells (EPI-NCSCs) and olfactory ensheathing cells (OECs) were transplanted into the contused spinal cord of rats separately or jointly at 1 week after injury. At 3 and 9 weeks posttransplantation, migration of the donor cells, expression of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) and functional recovery of the contused cord were determined by techniques of histopathology, quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry and Basso-Beattie-Bresnahan (BBB) score. The results showed that the migration and distribution of EPI-NCSCs in vivo were promoted by OECs at 3 weeks after transplantation, but they vanished at 9 weeks. The expression of BDNF and GDNF was significantly increased by co-transplantation at molecular and protein level. Although the expression of both factors in EPI-NCSCs- and OECs-injected group was lower than in co-injected group, it was higher than in control groups. Similarly, the best locomotor recovery of the contused cord was acquired from co-injected animals. As we know, this is the first time to study the synergic effects of EPI-NCSCs and OECs, and the data indicates that donor cells migration, expression of neurotrophic factors (NTFs), and recovery of motor function can be improved by EPI-NCSCs and OECs synergistically.