The impact of diabetes mellitus on mortality and infection outcomes in burn patients: a meta-analysis.

OBJECTIVE: Burns are one of the most commonly occurring soft tissue injuries worldwide. It has been reported that burns are associated with a higher prevalence of complications, mortality, and hospitalization-related outcomes in patients with coexisting diabetes mellitus. Moreover, the morbidity and mortality related outcomes associated with diabetes in patients with burns. However, since then, several studies reporting the prognostic role of diabetes in patients with burns have been published. Therefore, in this present study, we attempt to develop a current state of evidence evaluating the prognostic influence of diabetes mellitus on infectious complications, duration of hospital stay and mortality-related outcomes in patients with burns. The aim of the study is to determine the overall effect of diabetes mellitus on infectious complications, duration of hospital stay and mortality-related outcomes in patients with burns. MATERIALS AND METHODS: We performed a systematic search of the academic literature in four academic databases including EMBASE, CENTRAL, Scopus, and MEDLINE according to PRISMA guidelines. A random effect meta-analysis was carried out to evaluate the pooled effect size associated with diabetes mellitus on the outcome of infectious complications, duration of hospital stay and mortality in patients with burns. RESULTS: From a total of 1,397 studies, 13 eligible studies with 16,538 patients (3415F, 8361M) with burns were included in the analysis. Among these patients, 1702 patients had diabetes, and 14,836 patients were reported to be non-diabetic. A random effect meta-analysis revealed small-to-large size positive effect of diabetes on the infectious outcome (Hedge's g: 0.2, 95% CI: -0.03 to 0.44), overall mortality (0.16, -0.06 to 0.39), and duration of hospital stay (0.98, 0.50 to 1.45) in patients with burns. CONCLUSIONS: The present systematic review and meta-analysis provides evidence regarding the high morbidity and mortality related outcomes for diabetic patients with burns. The present study confirms the findings of a previously published systematic review suggesting diabetes to be an important and independent risk factor delineating the prognostic outcome of burns.

Correlated Dirac Eigenvalues and Axial Anomaly in Chiral Symmetric QCD.

We introduce novel relations between the derivatives [∂^{n}ρ(λ,m_{l})/∂m_{l}^{n}] of the Dirac eigenvalue spectrum [ρ(λ,m_{l})] with respect to the light sea quark mass (m_{l}) and the (n+1)-point correlations among the eigenvalues (λ) of the massless Dirac operator. Using these relations we present lattice QCD results for ∂^{n}ρ(λ,m_{l})/∂m_{l}^{n} (n=1, 2, 3) for m_{l} corresponding to pion masses m_{π}=160-55 MeV and at a temperature of about 1.6 times the chiral phase transition temperature. Calculations were carried out using (2+1) flavors of highly improved staggered quarks with the physical value of strange quark mass, three lattice spacings a=0.12, 0.08, 0.06 fm, and lattices having aspect ratios 4-9. We find that ρ(λ→0,m_{l}) develops a peaked structure. This peaked structure arises due to non-Poisson correlations within the infrared part of the Dirac eigenvalue spectrum, becomes sharper as a→0, and its amplitude is proportional to m_{l}^{2}. We demonstrate that this ρ(λ→0,m_{l}) is responsible for the manifestations of axial anomaly in two-point correlation functions of light scalar and pseudoscalar mesons. After continuum and chiral extrapolations we find that axial anomaly remains manifested in two-point correlation functions of scalar and pseudoscalar mesons in the chiral limit.

BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFß signaling pathway.

OBJECTIVE: In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis. MATERIALS AND METHODS: S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-ß. RESULTS: Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-ß levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-ß level was downregulated in the T5224 group when compared to those in the control group. CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-ß pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.

Brain Α-Tocopherol Concentration is Inversely Associated with Neurofibrillary Tangle Counts in Brain Regions Affected in Earlier Braak Stages: A Cross-Sectional Finding in the Oldest Old.

Objectives: Higher vitamin E status has been associated with lower risk of Alzheimer's disease (AD). However, evidence of the association of vitamin E concentration in neural tissue with AD pathologies is limited. Design: The cross-sectional relationship between the human brain concentrations of α- and γ-tocopherol and the severity of AD pathologies - neurofibrillary tangle (NFT) and neuritic plaque (NP) - was investigated. Setting & Participants: Brains from 43 centenarians (≥ 98 years at death) enrolled in the Phase III of the Georgia Centenarian Study were collected at autopsy. Measurements: Brain α- and γ-tocopherol concentrations (previously reported) were averaged from frontal, temporal, and occipital cortices. NP and NFT counts (previously reported) were assessed in frontal, temporal, parietal, entorhinal cortices, amygdala, hippocampus, and subiculum. NFT topological progression was assessed using Braak staging. Multiple linear regression was performed to assess the relationship between tocopherol concentrations and NP or NFT counts, with and without adjustment for covariates. Results: Brain α-tocopherol concentrations were inversely associated with NFT but not NP counts in amygdala (ß = -2.67, 95% CI [-4.57, -0.79]), entorhinal cortex (ß = -2.01, 95% CI [-3.72, -0.30]), hippocampus (ß = -2.23, 95% CI [-3.82, -0.64]), and subiculum (ß = -2.52, 95% CI [-4.42, -0.62]) where NFT present earlier in its topological progression, but not in neocortices. Subjects with Braak III-IV had lower α-tocopherol (median = 69,622 pmol/g, IQR = 54,389-72,155 pmol/g) than those with Braak I-II (median = 72,108 pmol/g, IQR = 64,056-82,430 pmol/g), but the difference was of borderline significance (p = 0.063). γ-Tocopherol concentrations were not associated with either NFT or NP counts in any brain regions assessed. Conclusions: Higher brain α-tocopherol level is specifically associated with lower NFT counts in brain structures affected in earlier Braak stages. Our findings emphasize the possible importance of α-tocopherol intervention timing in tauopathy progression and warrant future clinical trials.

CCAT2 contributes to progression and treatment resistance of thyroid carcinoma.

OBJECTIVE: The aim of this study is to uncover the correlations of the expression of colon cancer associated transcript 2 (CCAT2) in the clinical papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) specimens with the prognosis and chemoresistance of patients. PATIENTS AND METHODS: The expression level of CCAT2 in the PTC and ATC specimens was determined using Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), and the correlations of CCAT2 expression with the clinical features of patients were detected via χ2 test. Besides, survival analysis was conducted to verify the relation between CCAT2 expression and patients' survival. After knockdown or overexpression of CCAT2, the changes in the proliferation ability of human thyroid carcinoma cells were examined via Cell Counting kit-8 (CCK-8) assay, and the half maximal inhibitory concentration (IC50) values of doxorubicin and cisplatin were measured by methyl thiazolyl tetrazolium (MTT) assay. RESULTS: According to the χ2-test results, the expression of CCAT2 was notably correlated with the capsular invasion and lymph node metastasis of PTC, and the capsular invasion, tumor size, and lymph node metastasis of ATC. It was discovered through the survival analysis that the expression of CCAT2 was notably associated with the poor prognosis of ATC patients. After knockdown of CCAT2, both the proliferation ability and the IC50 values of doxorubicin and cisplatin substantially declined in human thyroid carcinoma cells. The opposite conditions were found after CCAT2 was overexpressed in human thyroid carcinoma cells. CONCLUSIONS: CCAT2 potentiates the proliferation ability and chemoresistance of cells, promotes the progression of thyroid carcinoma, and hinders the prognosis of ATC.

Wharton's Jelly-derived mesenchymal stem cells suppress apoptosis of nucleus pulposus cells in intervertebral disc degeneration via Wnt pathway.

OBJECTIVE: Aberrant apoptosis of nucleus pulposus cells (NPCs) is one of the most remarkable pathological changes in intervertebral disc degeneration (IDD) development. Albeit the advances in the application of stem cell-based therapy in IDD treatment, the molecular mechanisms underlying the anti-apoptotic actions of mesenchymal stem cell (MSC) remain poorly elucidated. PATIENTS AND METHODS: The expression patterns of apoptosis-related proteins and Wnt/ß-catenin-related genes in NP samples isolated from patients with mild or severe IDD were compared by performing immunoblot assay and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. NPCs were in vitro treated with compression to induce apoptosis and then co-cultured with Wharton's Jelly-derived MSCs without direct interaction. After that, flow cytometry was carried out to detect the apoptosis rate of NPCs and the activity of Wnt/ß-catenin pathway was determined. DKK-1 was used to inhibit Wnt signaling, in prior to evaluation of the effects of WJ-MSCs on apoptosis within the co-cultured NPCs. RESULTS: Compared to the mild IDD group, there was a significant increase in the expression of Caspase-3 and Bax in the NP tissues from severe IDD patients, whereas Bcl-2 displayed an opposite result. In addition, the expression of Wnt 3a, Wnt 5a, Wnt 10a, GSK-3ß, cyclinD1 and ß-catenin was notably augmented in parallel with IDD progression. After compression treatment, the proportion of apoptotic NPCs was increased, which was then dramatically reversed by WJ-MSCs co-culture. Likewise, WJ-MSCs suppressed compression-induced Wnt-related gene expression and blocking Wnt/ß-catenin pathway using DKK-1 enhanced the anti-apoptotic impacts of WJ-MSCs. In the presence of DKK-1, there was no significant difference between NPCs co-cultured with WJ-MSCs and those cells cultured alone. CONCLUSIONS: WJ-MSCs attenuate the compression-induced apoptosis in NPCs and inhibit the activation of Wnt/ß-catenin signaling. Blocking Wnt/ß-catenin pathway further facilitates the actions of WJ-MSCs in anti-apoptosis, indicating that Wnt/ß-catenin signaling plays a crucial role in this process and may function as a potential therapeutic target for IDD treatment.

Menaquinone-7 protects astrocytes by regulating mitochondrial function and inflammatory response under hypoxic conditions.

OBJECTIVE: Astrocytes play a key role in hypoxic brain injury. The aim of our research was to determine the effects of menaquinone-7 (MK-7), a subtype of vitamin K2 (VK2), on astrocytes during hypoxia and its potential mechanisms. MATERIALS AND METHODS: Astrocytes from the palliums of newborn Sprague Dawley rats were cultured. An astrocyte-hypoxia model was established using a hypoxia workstation. Cell Counting Kit-8 (CCK-8) and BrdU assays were used to determine the effects of MK-7 on hypoxic astrocytes. 2',7'-Dichlorodihydrofluorescein diacetate (DCFDA) or dihydroethidium (DHE) assays were conducted to detect the levels of reactive oxygen species (ROS). An ATP assay was used to measure intracellular ATP production. The levels of proinflammatory cytokines and chemokines containing interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), CC-chemokine ligand 2 (CCL2), and CXC-chemokine ligand 10 (CXCL10), as well as vitamin K-dependent protein growth arrest-specific 6 (Gas6), were determined in hypoxia-induced astrocytes, in the presence or absence of MK-7 pretreatment. Small interfering RNA (siRNA) was used to knockdown Gas6 expression to determine its role in hypoxic astrocytes pretreated with MK-7. RESULTS: Hypoxia reduced astrocyte viability and proliferation significantly; however, when pretreated with MK-7, these conditions remarkably increased. MK-7 also inhibited hypoxia-induced ROS production and enhanced ATP generation of hypoxic astrocytes. Pretreatment with MK-7 effectively reduced the expression of IL-6, TNF-α, CCL2, and CXCL10 but enhanced the expression of Gas6 in hypoxic astrocytes. Gas6 inhibition markedly attenuated the decline in MK-7-induced ROS generation and IL-6 expression, and weakened MK-7-induced cell viability and ATP production in hypoxic astrocytes. CONCLUSIONS: Our study is the first to confirm that MK-7 can protect astrocytes from hypoxia-induced cytotoxicity, possibly by inhibiting mitochondrial dysfunction and the expression of proinflammatory cytokines. Gas6 may also participate in these protective effects.

Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1, by X.-L. Cui, X.-D. Wang, S.-K. Lin, C.-M. Miao, M. Wu, J.-G. Wei, published in Eur Rev Med Pharmacol Sci 2019; 23 (19): 8449-8455-DOI: 10.26355/eurrev_201910_19157-PMID: 31646575" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19157.

MiR-532-5p acts as a tumor suppressor and inhibits glioma cell proliferation by targeting CSF1.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-532-5p acts as a tumor suppressor and inhibits glioma cell proliferation by targeting CSF1, by Y.-P. Wang, J. Liu, D. Liu, X.-D. Wang, A.-M. Bian, D.-Z. Fang, X.-B. Hui, published in Eur Rev Med Pharmacol Sci 2019; 23 (20): 8964-8970-DOI: 10.26355/eurrev_201910_19295-PMID: 31696484" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/19295.

LncRNA HANR aggravates the malignant progression of glioma via targeting miRNA-335.

OBJECTIVE: The aim of this study was to uncover the role of lncRNA HANR in the progression of glioma and the underlying mechanism. PATIENTS AND METHODS: HANR expression level in 36 matched glioma tissues and adjacent non-tumoral tissues was determined by qRT-PCR. The relationship between HANR expression and pathological indexes of the glioma patients was analyzed. The Kaplan-Meier method was introduced to investigate the survival of glioma patients. After the knockdown of HANR, the proliferative, migratory, and invasive changes of U251 and SHG44 cells were determined. Bioinformatics and Dual-Luciferase Reporter Gene Assay were applied to predict and verify the downstream target of HANR, respectively. Furthermore, the rescue experiments were conducted to clarify the role of HANR/miRNA-335 regulatory loop in the progression of glioma. RESULTS: HANR was significantly upregulated in glioma tissues and cell lines. Glioma patients with a high expression level of HANR presented remarkably higher rates of lymphatic metastasis and distant metastasis, as well as worse prognosis. The silence of HANR remarkably attenuated the proliferative, migratory, and invasive capacities of U251 and SHG44 cells. MiRNA-335 was the direct target of HANR and was significantly downregulated in glioma tissues. Meanwhile, the miRNA-335 level was negatively regulated by HANR. In addition, the knockdown of miRNA-335 partially reversed the regulatory effects of HANR on cellular behaviors of glioma. CONCLUSIONS: LncRNA HANR is upregulated in glioma, which is closely correlated with metastasis and poor prognosis of glioma patients. In addition, HANR aggravates the progression of glioma by negatively regulating miRNA-335.

Circ_0005075 stimulates the proliferation and metastasis of glioma via downregulating SIRT1.

OBJECTIVE: The aim of this study was to uncover the potential influence of circ_0005075 on the malignant progression of glioma and the underlying mechanism. PATIENTS AND METHODS: Circ_0005075 level in glioma tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relation between circ_0005075 expression and metastasis of glioma patients was analyzed. Prognostic potential of circ_0005075 in glioma was assessed by calculating overall survival (OS) and progression-free survival (PFS). After knockdown or overexpression of circ_0005075, changes in the viability, migration, and wound closure percentage of T98-G and U87 cells were examined, respectively. Subsequently, expression pattern and prognostic value of SIRT1 in glioma patients were determined. Furthermore, the involvement of SIRT1 in glioma progression affected by circ_0005075 was evaluated through rescue experiments. RESULTS: Circ_0005075 was significantly up-regulated in glioma tissues and cell lines. Meanwhile, its expression level was significantly higher in glioma patients with lymphatic metastasis or distant metastasis when compared with those with negative metastasis. OS and PFS were both remarkably worse in glioma patients with high expression level of circ_0005075. Knockdown of circ_0005075 decreased the viability, migration, and wound closure percentage of T98-G cells. However, overexpression of circ_0005075 in U87 cells yielded the opposite trends. SIRT1 expression level was negatively regulated by circ_0005075 in glioma. QRT-PCR results demonstrated that SIRT1 was significantly down-regulated in glioma tissues and cell lines. High level of SIRT1 predicted better prognosis of glioma patients. Rescue experiments confirmed that SIRT1 was responsible for the regulatory role of circ_0005075 in the malignant progression of glioma. CONCLUSIONS: Circ_0005075 is up-regulated in glioma tissues and correlated with distant metastasis and poor prognosis of glioma patients. Furthermore, it aggravates the malignant progression of glioma by down-regulating SIRT1.

MiR-30a-3p promotes ovariectomy-induced osteoporosis in rats via targeting SFRP1.

OBJECTIVE: To explore the effect of miR-30a-3p on osteoporosis in rats after ovariectomy. MATERIALS AND METHODS: The ovariectomized (OVX) rat model was established to mimic postmenopausal osteoporosis. The primary bone marrow mesenchymal stem cells (BMMSCs) isolated from female rats were transfected with mimic or inhibitor. Real Time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting were used to examine the expressions of miR-30a-3p and osteoporosis-related proteins. The bone mineral density (BMD) was detected via micro-Computed Tomography (CT) and the bone histomorphometry was performed. Luciferase assay was also performed to confirm whether SFRP1 is a target of miR-30a-3p. RESULTS: According to micro CT, BMD significantly declined in OVX group. MiR-30a-3p and SFRP1 were negatively correlated after ovariectomy. SFRP1 was acknowledged as a target of miR-30a-3p. Besides, the miR-30a-3p inhibitor promoted osteogenic differentiation in vitro and bone formation in vivo. CONCLUSIONS: MiR-30a-3p inhibitor promotes bone formation through decreasing SFRP1 expression and miR-30a-3p may be a potential novel molecular target in the treatment of osteoporosis.

MiR-532-5p acts as a tumor suppressor and inhibits glioma cell proliferation by targeting CSF1.

OBJECTIVE: Recent studies have discovered a class of micro-RNAs (miRNAs), which are dysregulated in various tumors and associated with carcinogenesis. In our research, we aim to uncover the molecular functions of miR-532-5p in glioma development. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was performed to detect miR-532-5p expression in 48 glioma samples and 4 glioma cell lines. The Pearson's Chi-square test was used to determine the association of miR-532-5p expression with several clinicopathological indexes in glioma patients. Besides, cell proliferation assay, colony formation assay, and Ethynyl deoxyuridine (EdU) incorporation assay were performed to explore in vitro effects of miR-532-5p on glioma cells. Furthermore, the interaction between miR-532-5p and CSF1 in glioma was studied by performing Western blot assay and Dual-Luciferase Reporter Gene Assay. RESULTS: Downregulated miR-532-5p expression was observed in glioma tissues compared with adjacent normal samples. MiR-532-5p expression was associated with the KPS score and tumor grading in glioma patients. Moreover, cell proliferation of glioma was inhibited after overexpression of miR-532-5p in vitro. Furthermore, CSF1 was a target of miR-532-5p in glioma. After overexpression of miR-532-5p, CSF1 was downregulated at mRNA and protein levels in vitro Besides, the expression of CSF1 in glioma tissues was negatively related to that of miR-532-5p. CONCLUSIONS: Malignant phenotypes of glioma cells were remarkably suppressed through the overexpression of miR-532-5p. MiR-532-5p/CSF1 axis was identified as a new therapeutic intervention for the treatment of glioma.

Circular RNA circ_0067934 functions as an oncogene in glioma by targeting CSF1.

OBJECTIVE: The importance of circular RNAs in malignant tumors increases the attention of researchers. The role of circ_0067934 in glioma remains unclear. Our study aims to uncover how circ_0067934 functions in glioma development. PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was utilized to determine the level of circ_0067934 in glioma tissues. Circ_0067934 was knocked down in glioma cells. Cell migrated and invaded ability was detected through functional assay in vitro and in vivo. Further mechanism assays were performed to explore the potential targets of circ_0067934. RESULTS: The circ_0067934 was highly expressed in glioma tissues compared with adjacent samples. The expression of circ_0067934 was upregulated in glioma cell lines. The cell migrated and invaded ability of glioma cells was inhibited after circ_0067934 was knocked down. Besides, CSF1 expression was decreased via knockdown of circ_0067934. Furthermore, tumor metastasis was inhibited after circ_0067934 was knocked down in nude mice. CONCLUSIONS: The circ_0067934 could suppress cell migration and invasion of glioma by upregulating CSF1.

MicroRNA-204-5p targets SOX11 to regulate the inflammatory response in spinal cord injury.

OBJECTIVE: The purpose of this study was to investigate whether microRNA-204-5p can regulate the inflammatory response of spinal cord injury (SCI) by targeting SOX11. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-204-5p in patients with SCI. The mouse SCI model was established to detect the recovery of the grip strength of the upper and lower limbs. Then, the expression of microRNA-204-5p in these mice with SCI was detected by qRT-PCR, and the levels of the inflammatory factors Toll-like receptor 4 (TLR4) and iNOS were examined by Western blot. Subsequently, microRNA- 204-5p was overexpressed in the mouse SCI model using lentivirus, and the changes in mouse grip strength and the inflammatory factor levels were observed. SOX11 was then searched as the target gene of microRNA-204-5p through bioinformatics analysis, and its expression in patients or mice with SCI was examined using qRT-PCR. SOX11 expression was again detected after the overexpression or knockdown of microRNA-204-5p in cells. The binding of microRNA-204-5p to SOX11 was verified by dual-luciferase reporting assay. After microRNA-204-5p and SOX11 were co-overexpressed in cells, the levels of TLR4 and iNOS were analyzed. Furthermore, the changes in the grip strength were observed in mice with SCI after simultaneous up-regulation of microRNA-204-5p and SOX11. RESULTS: Micro-204-5p level was conspicuously decreased in the population with SCI. And the SCI mouse model showed that the upper and lower limb strength conspicuously decreased and began to recover after 7 days. During the seven days, microRNA-204-5p level in the SCI mice decreased with time, while the levels of the inflammatory cytokines TLR4 and iNOS conspicuously increased. After microRNA-204-5p was overexpressed in SCI mice, their upper and lower limb strength was conspicuously restored, while the levels of TLR4 and iNOS were also remarkably decreased. The bioinformatics analysis revealed that there exist some binding sites between microRNA-204-5p and SOX11, and we found that SOX11 expression was conspicuously enhanced in the plasma of the SCI patients. Meanwhile, the SOX11 level in SCI mice was also conspicuously increased, and it was time-dependent. The expression of SOX11 was decreased after the upregulation of microRNA-204-5p, while the opposite result was observed after the downregulation of microRNA-204-5p. In addition, the result of the dual-luciferase reporter gene assay revealed that microRNA-204-5p could bind to SOX11 in a targeted manner. Meanwhile, the up-regulation of SOX11 was partially relieved by the inhibitory effect of microRNA-204-5p on TLR4 and iNOS. Moreover, the simultaneous overexpression of SOX11 and microRNA-204-5p partially reversed the impact of the up-regulated microRNA-204-5p alone on the recovery of the upper and lower limb strength in SCI mice. CONCLUSIONS: The low expression of microRNA-204-5p in patients with SCI can affect the levels of the inflammatory cytokines TLR4 and iNOS and improve SCI by targeting SOX11.

Expression of miR-31 in rectal cancer patients and its effect on proliferation ability of rectal cancer cells SW837.

OBJECTIVE: This study aimed to investigate the expression of miR-31 in rectal cancer patients and its effect on the proliferation and invasion ability of human rectal cancer cells SW837. PATIENTS AND METHODS: 55 rectal cancer cancerous tissue specimens and 55 corresponding adjacent tissue (tissue adjacent to carcinoma) specimens were collected from rectal cancer patients treated in The First Hospital of Jilin University from March 2014 to March 2015. Real Time-quantitative Polymerase Chain Reaction was used for detecting the expression level of miR-31 in cancerous tissue and corresponding adjacent tissues. Differences in the expression of miR-31 were compared between the two groups. Different miR-31 expression vectors were established and rectal cancer cells SW837 were transfected. MTT was used for detecting the proliferation ability of the cells in the miR-31-mimics group, miR-31-inhibitor group and miR-control group. RESULTS: The expression level of miR-31 was significantly higher in rectal cancer tissues than that in the adjacent tissues (p<0.05). The expression of miR-31 was higher in the miR-31-mimics group (23.6±4.6) than that in the miR-control group (1.63±0.65), while the expression of miR-31 was lower in the miR-31-inhibitor group (0.65±0.23) than that in the miR-control group. The proliferation ability of cells at the 6th, 12th, 24th, 48th, and 72nd hours was higher in the miR-31-mimics group than in the miR-31-inhibitor group, while that of cells was significantly lower in the miR-31-inhibitor group than in the miR-control group, with statistically significant differences (p<0.05). The number of invasive membrane cells (cell membrane number) counted under a microscope was (84.2±10.6) cells in the miR-31-mimics group, (12.3±4.1) cells in the miR-31-inhibitor group, and (45.2±10.6) cells in the miR-control group. The invasion ability in vitro of SW837 cells significantly increased after the overexpression of miR-31 (p<0.05). CONCLUSIONS: miR-31 is increasingly expressed in rectal cancer. Low expression of miR31 can inhibit the proliferation and invasion ability of the cells. MiR-31 is expected to become a current biotherapeutic target.

MiR-223 promotes cardiomyocyte apoptosis by inhibiting Foxo3a expression.

OBJECTIVE: MicroRNAs (miRs) are proven to possess diversified functions in the pathogenesis of cardiac diseases. The current study is designed aiming at determining the effect of miR-223 on oxidative stress induced apoptosis in cardiomyocytes. MATERIALS AND METHODS: Mouse model of myocardial infarction (MI) was constructed, and endogenous level of miR-223 in the border zone of infarcted heart tissues was determined. Primarily cultured cardiomyocytes were exposed to H2O2 treatment to mimic the oxidative stress stimulation. Multiple approaches including quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell viability assay, luciferase assay, Western blot assay and flow cytometry assay were employed to determine its expression, function and mechanism in apoptosis. RESULTS: MiR-223 expression was significantly upregulated in the border zone of infarcted heart ventricular tissues and in cardiomyocytes treated with H2O2. Overexpression of miR-223 in cardiomyocytes promoted apoptosis, whereas inhibition of endogenous miR-223 protected cardiomyocytes from oxidative stress induced apoptosis. MiR-223 directly targets the 3'untranslated region (UTR) of Foxo3a mRNA. Overexpression of miR-223 inhibited Foxo3a protein expression, however, inhibition of miR-223 suppressed its expression. Silencing Foxo3a using small interfering RNA (siRNA) mimicked the effect of miR-223, indicating its functional significance. CONCLUSIONS: MiR-223 is an important regulator of cardiomyocyte apoptosis under oxidative stress. Inhibition of the miR-223/Foxo3a signaling axis may be a potential therapeutic strategy for cardiac injuries.

Analysis the effect of hyperbaric oxygen preconditioning on neuronal apoptosis, Ca2+ concentration and caspases expression after spinal cord injury in rats.

OBJECTIVE: To investigate the effects of hyperbaric oxygen preconditioning (HBO-PC) on neuronal apoptosis, Ca2+ concentration, and Caspases expression after spinal cord injury (SCI) in rats. MATERIALS AND METHODS: A total of 36 rats were randomly divided into control group (CON group), hyperbaric oxygen preconditioning group (HBO-PC group) and spinal cord injury group (SCI group), with 12 rats in each group. Rats in group HBO-PC were given HBO-PC intervention before modeling. SCI model was established by modified Allen method in group HBO-PC and group SCI. Basso-Beattie-Bresnahan (BBB) locomotor rating scale and motor evoked potential (MEP) examination were used to assess the neurological function. The expression of apoptosis gene caspase (3, 7, 8, 12) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). The concentration of Ca2+ in spinal cord tissue of each group was detected. RESULTS: CON group, HBO-PC group, and SCI group were gradually diminishing in BBB score and potential value and amplitude of MEP, respectively. The differences between groups were statistically significant (p<0.05). The expressions of Caspase-3 and 7, 8 and 12 mRNA in SCI group were significantly higher than those in CON group and HBO-PC group, respectively (p<0.05). There was no significant difference between CON group and HBO-PC group (p>0.05). The concentrations of Ca2+ in the CON group, HBO-PC group and SCI group were gradually increased; differences between groups were statistically significant (p<0.05). CONCLUSIONS: HBO-PC can reduce the loss of motor function of SCI rats, which may inhibit the activation of endoplasmic reticulum pathway of neural apoptosis, and reduce the calcium overload through inhibiting the expressions of pro-apoptotic proteins (Caspase-3/7/8/12), thus reducing the cell apoptosis and protecting neurons.

MicroRNA-129-3p suppresses tumor growth by targeting E2F5 in glioblastoma.

OBJECTIVE: Neuroma is the most common intracranial tumor. The mechanism of miRNA in glioma has gradually been understood. The purpose of this study was to investigate the role of MicroRNA-129-3p (miR-129-3p) in the pathogenesis of glioblastoma (GBM). PATIENTS AND METHODS: Differential expression of miR-129-3p in samples was analyzed by bioinformatics. PCR was used to detect the expression of miR-129-3p in samples. CCK8 assay was used to detect the cell viability. Transfection of mimic and inhibitor altered the expression of miR-129-3p, and the biological function of miRNA was explored. Luciferase reporter gene was used to detect target genes of miRNA. E2F5 expression was inhibited by transfection of small interfering RNAs. Western blotting was used to detect protein expressions of cells. RESULTS: miR-129-3p was low-expressed in the tissue samples. By transfecting mimic and the inhibitor, we found that increasing the expression of miR-129-3p can inhibit the cell viability. In contrast, inhibition of miR-129-3p promoted cell growth. Luciferase reporter gene and Western blot results suggested that E2F5 can be used as the target gene of miR-129-3p. Knockdown the target gene of the miR-129-3p, E2F5, also inhibited proliferation of glioblastoma. CONCLUSIONS: miR-129-3p can inhibit the growth of glioblastoma by down-regulating the expression of E2F5. miR-129-3p can be a new target for the treatment of glioblastoma. Our research provides new ideas for the target therapy of glioma.