Spinal cord injury (SCI) usually results in a large range of sensorimotor and autonomic nerve injury and remains a serious public health problem worldwide. SCI affects approximately 273 000 people in the United States, and there are some 12 000 new cases each year. 1-3 Therefore, SCI brings severe economy burdens and psychological pressure to patients. However, there are currently no effective therapies for SCI clinically, and an effective treatment is awaited. 4-6 This is due mainly to the molecular mechanisms of SCI remain elusive. The pathological process of SCI is known as a complex process, which can be classified into two phases: Primary injury is the direct mechanical damage of spinal cord tissue and includes demyelination and necrosis of neurons and axons; and the secondary injury is composed of a variety of pathophysiologic mechanisms, including local haemorrhage, ischaemia, oedema, ionic imbalance, free radical stress and inflammatory responses. 7,8 This complex pathological process of SCI may explain the difficulty in finding a suitable and effective therapy. Therefore, understanding the molecular mechanisms of SCI is critical for the development of therapeutic strategies. Cell death is known as the final stage of cells and it can be resulted from cytotoxicity from exogenous or endogenous substances. 9 In 1842, cell death was first posed by Carl Vogt, and lots of molecules are considered to be involved in this irreversible process to support the maintenance of cellular homeostasis. 10 Cell death was initially divided into two types, necrosis and apoptosis. 11 Necrosis is considered as a passive and accidental cell death, which can be resulted from environmental perturbations and the large amounts

Background: Spinal cord injury (SCI) is a severe condition that disrupts patients' physiological, mental, and social well-being state and exerts great financial burden on patients, their families and social healthcare system. This review intends to compile studies regarding epidemiological features of SCI in China.Methods: Searches were conducted on PubMed, EMBASE, Web of Science and Cochrane Library for relevant studies published through January, 2018. Studies reported methodological and epidemiological data were collected by two authors independently.Results: Seventeen studies met the inclusion criteria. Two studies reported incidence of SCI that is 60.6 in Beijing (2002) and 23.7 in Tianjin (2004–2008). All studies showed male had a larger percentage in SCI compared to female except Taiwan (2000–2003). The average male and female ratio was 3–4:1 in China and the highest male and female ratio was 5.74: 1 in Tianjin (2004–2007). Farmers, laborers and unemployed people accounted for more than half of the SCI patients in China. Fall was the primary causation with exception of Heilongjiang (2009–2013), Beijing (2001–2010), and Taiwan (2002–2003), where motor vehicle collision (MCVs) was the leading causation. Pulmonary infection, urinary tract infection and bedsore were common complications, accounting for approximately 70% of SCI patients in China.Conclusion: This review shows that epidemiological features of SCI are various in different regions in China and prevention should be implemented by regions. The number of patients with SCI result from fall and MCVs may become a main public health problem because population aging and economic developing in China. However, because all included studies were retrospective and lacking a register system in China, some data were incomplete and some cases may be left out, so the conclusion may not be generalizable to the other regions.

Neural stem cells (NSCs) are self-renewing, pluripotent, and undifferentiated cells which have benefits as candidates for central nervous system (CNS) injury. However, the transplanted NSCs usually maintain their undifferentiated characteristics, or differentiated potentially along the glial lineage after transplantation. MicroRNAs (miRNAs) are small, non-coding RNAs that play key roles in cell differentiation. However, it is unknown whether miR-29a could play a role in the process of NSC's differentiation. Primary NSCs were derived from rat embryonic cortex. Lentiviral vector-mediated miR-29a (LV-miR-29a) and negative control (LV-null) were infected into NSCs. Quantitative real-time PCR was used to detect expression of miR-29a and PTEN. Immunocytochemistry was used to stain neurons, astrocytes, and oligodendrocytes. Dual luciferase assay to study the interaction between miR-29a and PTEN. The current study showed that the expression of miR-29a was upregulated during NSC differentiation, while the expression of PTEN was downregulated during NSC differentiation. After infection with LV-miR-29a, MAP-2-positive neurons significantly increased, and GFAP-positive astrocytes significantly decreased. Furthermore, we demonstrated that PTEN is a molecular target of miR-29a. miR-29a promote the neuronal differentiation and decrease the astrocytes differentiation of NSCs via targeting PTEN. This may give insight into a novel mechanism of NSC differentiation and provide a promising therapeutic target.

Tumor associated macrophages (TAMs) are a major type of inflammatory cell in a tumor microenvironment. Previous evidence has suggested that TAMs promote tumorigenesis, growth, invasion and metastasis, thereby affecting tumor metabolism. The mechanisms through which they affect the invasion and metastasis of lung cancer cells remain unclear. The present study investigated the effects and molecular mechanisms of TAMs on the proliferation, invasion and migration of lung adenocarcinoma A549 cells. Human mononuclear leukemia THP-1 cells were induced into TAMs. The morphological changes that occurred during the induction of the THP-1 cells were examined with a light microscope. Successful TAM formation was confirmed via flow cytometry. Proliferation, invasion and migration of the lung adenocarcinoma A549 cells were detected by EDU proliferation, scratch wound and Transwell invasion and migration assays, respectively. The expression levels of key proteins involved in the PI3K/AKT signaling pathway were detected by western blot analysis. It was identified that treatment with interleukin (IL)-4, IL-13 and Phorbol-12-myristate-13-acetate successfully induced THP-1 to form TAMs. The indirect coculture model of TAMs was established by Transwell chamber detection, and the proliferation, invasion and migration ability of lung adenocarcinoma A549 cells were enhanced. Western blot analysis indicated that the expression levels of phosphorylated (p)-PI3K and p-AKT proteins were significantly upregulated in the TAMs coculture group compared with that of the blank control group. In summary, the present study demonstrated that TAMs may promote the proliferation, invasion and migration of lung adenocarcinoma A549 cells in vitro , perhaps through the activation of the PI3K/AKT signaling pathway.

Spinal cord injury (SCI) is a highly severe disease and it can lead to the destruction of the motor and sensory function resulting in temporary or permanent disability. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt that play a critical role in central nervous system (CNS) injury. However, the exact roles of lncRNAs and messenger RNAs (mRNAs) in the early acute phase of SCI remain to be elucidated. We examined the expression of mRNAs and lncRNAs in a rat model at 2 days after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. Subsequently, a comprehensive bioinformatics analysis was also performed to clarify the interaction between DE mRNAs. A total of 3,193 DE lncRNAs and 4,308 DE mRNAs were identified between the injured group and control group. Classification, length distribution, and chromosomal distribution of the dysregulated lncRNAs were also performed. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. A protein−protein interaction (PPI) network indicated that IL6, TOP2A, CDK1, POLE, CCNB1, TNF, CCNA2, CDC20, ITGAM, and MYC were the top 10 core genes. The subnetworks from the PPI network were identified to further elucidate the most significant functional modules of the DE mRNAs. These data may provide novel insights into the molecular mechanism of the early acute phase of SCI. The identification of lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for SCI.

The tumor stromal microenvironment is an integral part of the occurrence and development of tumor. Cancer-associated fibroblasts (CAFs) are a key component of most tumor stromal microenvironments. The present study aimed to investigate the use of CAFs-targeted immunotherapy to fibroblast activation protein-α (FAP-α) expressed in CAFs. Recombinant adenoviral vectors containing the mouse FAP-α cDNA (rAd-FAP-α) were constructed. C57BL/6 mice were immunized with rAd-FAP-α infected dendritic cells (DCs) against FAP-α, which is overexpress in CAFs. The results demonstrated that mice vaccinated with rAd-FAP-α DCs gave rise to potent FAP-α-specific cytotoxic T lymphocytes capable of lysing Lewis lung cancer (LLC) CAFs. Furthermore, mice vaccinated with rAd-FAP-α-transduced DCs induced an effective therapeutic or protective antitumor immunity to LLC in a subcutaneous model, and prolonged overall survival time compared with mice vaccinated with the control recombinant adenovirus-transduced DCs (rAd-c DCs) or DCs alone. The results of the present study suggested that FAP-α, which is preferentially expressed in CAFs, may be considered as a potential target for killing or destroying CAFs within the tumor stromal microenvironment, and may be exploited to develop immunogenic tumor vaccines.

No abstract

No abstract