Network pharmacology and experimental verification revealing valnemulin alleviates DSS-induced ulcerative colitis by inhibiting intestinal senescence.

Ulcerative colitis (UC) is a chronic inflammatory disease that is increasing in prevalence globally. Senescence is characterized by a specific chronic, low-grade, "sterile" inflammatory state known as inflammaging, suggesting that senescence may exacerbate the severity of UC. However, the link between UC and senescence remains unclear. Valnemulin (VAL) is a semi-synthetic derivative of a naturally occurring diterpenoid antibiotic (pleuromutilin), which can inhibit peptidyl transferase. Studies investigating the potential of valnemulin to inhibit senescence and alleviate colitis are currently limited. In this study, we revealed that dextran sulfate sodium (DSS), an inducer of UC, induces senescence in both colon epithelial NCM460 cells and colon tissues. Additionally, VAL, identified from a compound library, exhibited robust anti-senescence activity in DSS-treated NCM460 cells. Identified in our study as an anti-senescence agent, VAL effectively mitigated DSS-induced UC and colonic senescence in mice. Through network pharmacology analysis and experimental validation, the potential signaling pathway (AMPK/NF-κB) for VAL in treating UC was identified. We discovered that DSS significantly inhibited the AMPK signaling pathway and activated the NF-κB signaling pathway. However, supplementation with VAL remarkably restored AMPK activity and inhibited the NF-κB signaling pathway, which led to the inhibition of senescence. In summary, our study demonstrated that DSS-induced UC stimulates the senescence of colonic tissues, and VAL can effectively alleviate DSS-induced colonic damage and reduce colonic senescence. Our research findings provide a new perspective for targeting anti-senescence in the treatment of UC.

Tedizolid phosphate alleviates DSS-induced ulcerative colitis by inhibiting senescence of cell and colon tissue through activating AMPK signaling pathway.

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease. Previous studies have suggested a link between senescence process and the body's inflammatory reaction, indicating that senescence may exacerbate UC, yet the relation between UC and senescence remains unclear. Tedizolid Phosphate (TED), a novel oxazolidinone antimicrobial, is indicated in acute bacterial skin infections, its impact on senescence is not known. Our research revealed that the UC inducer dextran sulfate sodium (DSS) triggers senescence in both colon epithelial NCM460 cells and colon tissues, and TED that screened from a compound library demonstrated a strong anti-senescence effect on DSS treated NCM460 cells. As an anti-senescence medication identified in this research, TED efficiently alleviated UC and colonic senescence in mice caused by DSS. By proteomic analysis and experimental validation, we found that DSS significantly inhibits the AMPK signaling pathway, while TED counteracts senescence by restoring AMPK activity. This research verified that the development of UC is accompanied with colon tissue senescence, and TED, an anti-senescence medication, can effectively treat UC caused by DSS and alleviate colon senescence. Our work suggests anti-senescence strategy is an effective approach for UC treatment.

MSCs-derived exosomes containing miR-486-5p attenuate cerebral ischemia and reperfusion (I/R) injury.

OBJECTIVES: This study aims to investigate the impact of mesenchymal stem cell (MSC)-derived exosomes (Exo) on cerebral ischemia and reperfusion (I/R) injury, along with the underlying mechanism. METHODS: An animal model of cerebral ischemia was induced using middle cerebral artery occlusion (MCAO), and a cell model utilizing Neuro-2a cells was established through oxygen-glucose deprivation/reoxygenation (OGD/R). Exosomes isolated from mouse MSCs were administered to mice or used to stimulate Neuro-2a cells. Exosomes from MSCs transfected with miR-NC, miR-486-5p mimics, miR-486-5p inhibitor, or phosphatase and tensin homolog (PTEN) short hairpin RNAs (sh-PTEN) were employed to stimulate Neuro-2a cells. The regulatory axis of miR-486-5p and PTEN was confirmed through rescue experiments. RESULTS: Exo-miR-486-5p mimics alleviated cerebral I/R injury, improving neurological deficits and reducing the infarct ratio. Furthermore, Exo-miR-486-5p mimics attenuated OGD/R-induced defects in cell viability and inhibited apoptosis in Neuro-2a cells. These mimics also reduced levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while enhancing superoxide dismutase (SOD) activity, both in brain tissue homogenates of mice and cell supernatants. Mechanistically, PTEN was identified as a target of miR-486-5p, and the downregulation of PTEN notably elevated Exo-miR-486-inhibitor-induced reductions in cell viability while mitigating cell apoptosis. CONCLUSION: The results of this study demonstrate the potential of exosomes derived from MSCs to protect against cerebral I/R injury via the miR-486-5p and PTEN axis.

Complete chloroplast genomes and comparative analysis of Ligustrum species.

In this study, we assembled and annotated the chloroplast (cp) genomes of four Ligustrum species, L. sinense, L. obtusifolium, L. vicaryi, and L. ovalifolium 'Aureum'. Including six other published Ligustrum species, we compared various characteristics such as gene structure, sequence alignment, codon preference, and nucleic acid diversity, and performed positive-selection genes screening and phylogenetic analysis. The results showed that the cp genome of Ligustrum was 162,185-166,800 bp in length, with a circular tetrad structure, including a large single-copy region (86,885-90,106 bp), a small single-copy region (11,446-11,499 bp), and a pair of IRa and IRb sequences with the same coding but in opposite directions (31,608-32,624 bp). This structure is similar to the cp genomes of most angiosperms. We found 132-137 genes in the cp genome of Ligustrum, including 89-90 protein-coding genes, 35-39 tRNAs, and 8 rRNAs. The GC content was 37.93-38.06% and varied among regions, with the IR region having the highest content. The single-nucleotide (A/T)n was dominant in simple-sequence repeats of the Ligustrum cp genome, with an obvious A/T preference. Six hotspot regions were identified from multiple sequence alignment of Ligustrum; the ycf1 gene region and the clpP1 exon region can be used as potential DNA barcodes for the identification and phylogeny of the genus Ligustrum. Branch-site model and Bayes empirical Bayes (BEB) analysis showed that four protein-coding genes (accD, clpP, ycf1, and ycf2) were positively selected, and BEB analysis showed that accD and rpl20 had positively selected sites. A phylogenetic tree of Oleaceae species was constructed based on the whole cp genomes, and the results were consistent with the traditional taxonomic results. The phylogenetic results showed that genus Ligustrum is most closely related to genus Syringa. Our study provides important genetic information to support further investigations of the phylogenetic development and adaptive evolution of Ligustrum species.

Effectiveness and Biomechanical Analysis of the Ortho-Bridge System on Femoral Fracture Healing: A Retrospective Analysis.

Background: Among the surgical methods for femoral fractures, the Ortho-Bridge System (OBS) appears to heal fractures via an uncommon process. We compared its effectiveness and biomechanical aspects to those of a locking compression plate (LCP) and explained the healing process demonstrated by the OBS. Methods: Eleven femoral shaft fracture cases treated with OBS between July 2017 and May 2020 were retrospectively reviewed. Clinical and radiographic data were collected during regular postoperative follow-up visits and assessed via the Harris Hip Score and Knee Society Score. We performed biomechanical experiments of OBS. We simulated different fracture conditions and selected appropriate screw holes at the fracture's far and near segments. The OBS module was placed according to the position of LCP's locking hole at both ends of the fracture; then, a static three-point bending test was performed. Results: All patients had contralateral callus growth with secondary fracture healing. Healing time was 3-5 months with excellent hip and knee function. When the key screw distance was 22-34 mm, the OBS was significantly less stiff than the LCP (P < 0.05). The stiffness of LCP and OBS decreased significantly when the key screw distance was 49-82 mm, with the LCP being slightly stronger (P < 0.05). Conclusions: Femoral shaft fracture treatment with OBS demonstrated secondary healing. When the distance between the key screws was 20-40 mm, the elasticity was higher in OBS than in LCP, possibly producing axial micro-motion to stimulate callus formation and promote fracture healing, which differ from the plate's primary healing process.

Femoral periprosthetic fracture treatment using the Ortho-Bridge System: a biomechanical study.

BACKGROUND: We undertook a comparative biomechanical study of type B1 fractures around femoral prostheses following cemented hip arthroplasty using the Ortho-Bridge System (OBS) and a locking compression plate/locking attachment plate structure (LCP + LAP). We aimed to investigate the biomechanical characteristics and advantages of the OBS compared with LCP + LAP when treating this fracture type. METHODS: An OBS fixation model was designed based on OBS and LCP + LAP fixation characteristics. The LCP + LAP combination (Group A) and three different OBS combinations (Groups B, C, and D) were used to fix a B1 fracture model with a femoral periprosthetic fracture. Axial compression and torsion experiments were then performed using simple and comminuted fracture models. The axial compression failure experiment was carried out, and the model stiffness during axial compression, torsion angle in torsion test, and vertical load in the final failure test were collected. RESULTS: When simulating simple oblique fractures, no significant difference was found among the four groups in terms of stiffness in the axial compression experiment (P = 0.257). The torsion angle of the LCP + LAP system was significantly higher compared with the OBS system (P < 0.05). When simulating a comminuted fracture, the experimental data for axial compression showed that the rigidity measurements of the three combinations of the OBS system were higher compared with the LCP + LAP system (P = 0.000) and that the torsion angles of three combinations of the OBS system were smaller compared with the LCP + LAP system (P < 0.05). In the axial compression failure test, the fixed failure mode of the LCP + LAP system was the destruction of the contact cortex at the fracture site, whereas the failure modes in the three OBS combinations involved fracture around the screws above the osteotomy and destruction of the contact cortex at the fracture site. CONCLUSIONS: The findings revealed that the OBS produced superior biomechanical outcomes compared with LCP + LAP, especially for the bridging two-rod dual cortex. According to the performance observed after model axial compression destruction, the OBS was fixed and provided greater stress dispersion, which might make it more suitable for facilitating early functional movement and avoiding the failure of internal fixation.

Strategic C-C Bond-Forming Dearomatization of Pyridines and Quinolines.

A one-pot protocol for the dearomative double nucleophilic addition to pyridines and quinolines, providing convenient, regioselective and diastereoselective access to tetrahydropyridines and tetrahydroquinolines under reductant-free conditions is described. This method also offers a new strategy for the general dearomatization of nitrogen heteroaromatics.

Occipital artery to upper posterior circulation bypass through the presigmoid approach in revascularization of the posterior circulation: An anatomical study.

We describe a novel extracranial (EC)-to-intracranial (IC) bypass technique between the occipital artery and upper posterior circulation (UPC) for revascularization of the posterior circulation through the presigmoid approach. Five formalin-fixed human heads were examined to demonstrate the detailed anatomy of the occipital artery and UPC and illustrate the step-by-step bypass procedure. The occipital artery, a branch of the external carotid artery, can be anastomosed to the P2/P3 segment of the posterior cerebral artery and S1/S2 segments of the superior cerebellar artery as an alternative to EC bypass donor segments for treatment of affection requiring revascularization. Presigmoid approach for the anastomosis of the occipital artery to the UPC provides a shorter distance, due to resection of some bones.

Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein.

Genistein, a potent antioxidant compound, protects dopaminergic neurons in a mouse model of Parkinson's disease. However, the mechanism underlying this action remains unknown. This study investigated human SH-SY5Y cells overexpressing the A53T mutant of α-synuclein. Four groups of cells were assayed: a control group (without any treatment), a genistein group (incubated with 20 µM genistein), a rotenone group (treated with 50 µM rotenone), and a rotenone + genistein group (incubated with 20 µM genistein and then treated with 50 µM rotenone). A lactate dehydrogenase release test confirmed the protective effect of genistein, and genistein remarkably reversed mitochondrial oxidative injury caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels were markedly higher in the genistein group than in the rotenone group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with the control group, the expression of NFE2L2 and HMOX1 was significantly increased in the genistein + rotenone group. However, after treatment with estrogen receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively), genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed phosphorylation of AKT, a protein downstream of the estrogen receptor. These findings confirm that genistein has neuroprotective effects in a cell model of Parkinson's disease. Genistein can reduce oxidative stress damage and cell apoptosis by activating estrogen receptors and NFE2L2 channels.

Exendin-4 inhibits high-altitude cerebral edema by protecting against neurobiological dysfunction.

The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 µg of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.

Access to 8-Azachromones via Activation of C-H in N-Oxides.

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

Strategic Approach to 8-Azacoumarins.

8-Azacoumarins have emerged as a promising class of compounds but are rarely explored due to challenging access. A novel, general, and practical method is provided for this class of compounds. The key lactonization step employs trans-acrylic acid attached pyridine N-oxides as the starting material, with acetic anhydride as both the activation agent and the solvent. Multiple transformations were involved in this reaction, including conjugate addition, nucleophilic aromatic substitution, and elimination. These studies provide the basis for access to 8-azacoumarins, enabling future work including the discovery and development of novel coumarin-type drugs, fluorescent probes, photolabile protecting groups, and other active molecules.

Diagnosis and treatment of a dural arteriovenous fistula presenting with progressive parkinsonism and dementia: A case report and literature review.

A dural arteriovenous fistula (DAVF) presenting with parkinsonism and dementia is rare; thus, is easily misdiagnosed. The present study reports the case of a 62-year-old male with mobility disabilities and a cognitive disorder. The initial symptoms were progressive symmetrical limb stiffness and weakness without significant limb tremor, and subsequently the appearance of progressive memory loss, behavioral abnormalities and a decline in the activities of daily living. Cranial magnetic resonance imaging (MRI) revealed an enlarged vascular shadow at the meninges of the left temporal lobe. In addition, digital subtraction angiography (DSA) revealed a DAVF in the left temporal region, fed by the bilateral middle meningeal arteries and meningeal branches of the vertebral artery, which were enlarged abnormally, with poor venous reflux to the superior sagittal sinus. The patient was treated with transarterial embolization therapy. Intraoperative angiography showed almost complete embolization of the DAVF. At day 3 following the surgery, the muscle tension of the bilateral limbs decreased significantly. After two weeks, the memory ability of the patient had recovered to the level prior to the onset, and the gait was stable. At one month post-surgery, the patient was able to take care of himself completely, and after three months, a stereotactic treatment was conducted for the residual fistula. At the one year follow-up, neurological examination revealed that the patient had recovered normally. In conclusion, progressive parkinsonism and dementia with an abnormal flow void shadow on cranial MRI films should be considered as a possible diagnosis of a DAVF. In these cases, DSA and endovascular treatment are recommended as soon as possible.

Recombinant human erythropoietin improves the neurofunctional recovery of rats following traumatic brain injury via an increase in circulating endothelial progenitor cells.

Previous studies show that circulating endothelial progenitor cells (EPCs) promote angiogenesis, which is a process associated with improved recovery in animal models of traumatic brain injury (TBI), and that recombinant human erythropoietin (rhEPO) plays a protective role following stroke. Thus, it was hypothesized that rhEPO would enhance recovery following brain injury in a rat model of TBI via an increase in the mobilization of EPCs and, subsequently, in angiogenesis. Flow cytometry assays using CD34- and CD133-specific antibodies were utilized to identify alterations in EPC levels, CD31 and CD34 antibody-stained brain tissue sections were used to quantify angiogenesis, and the Morris water maze (MWM) test and the modified Neurological Severity Score (mNSS) test were used to evaluate behavioral recovery. Compared with saline treatment, treatment with rhEPO significantly increased the number of circulating EPCs on days 1, 4, 7, and 14 (P < 0.05), improved spatial learning ability on days 24 and 25 (P < 0.05), and enhanced memory recovery on day 26 (P < 0.05). Moreover, rhEPO treatment decreased mNSS assessment scores on days 14, 21, and 25 (P < 0.05). There was a strong correlation between levels of circulating EPCs and CD34- and CD31-positive cells within the injured boundary zone (CD34(+) r = 0.910, P < 0.01; CD31(+) r = 0.894, P < 0.01) and the ipsilateral hippocampus (CD34(+) r = 0.841, P < 0.01; CD31(+) r = 0.835, P < 0.01). The present data demonstrate that rhEPO treatment improved functional outcomes in rats following TBI via an increase in the mobilization of EPCs and in subsequent angiogenesis.

Interactions of connexin 43 and aquaporin-4 in the formation of glioma-induced brain edema.

Connexin 43 (Cx43) and aquaporin-4 (AQP4) have important roles in the formation of glioma-induced brain edema; however, the association between these two factors in the development of edema has remained to be elucidated. In the present study, immunofluorescence and western blot analysis revealed that in a rat model of intracranial C6 glioma, Cx43 expression levels were low to undetectable and AQP4 expression levels were low in glioma cells. Significantly higher Cx43 and AQP4 levels were detected in the tissue surrounding the glioma. To further investigate the potential interaction between Cx43 and AQP4, normal glial cells and C6 glioma cells were cultured in hypotonic medium. Reverse transcription quantitative polymerase chain reaction indicated that AQP4 and Cx43 mRNA expression levels increased as a function of time in normal glial cells and C6 glioma cells in a hypotonic environment. However, the increase observed in normal glial cells was significantly lower than that observed in C6 glioma cells. Furthermore, AQP4 expression levels changed prior to alterations in Cx43 expression. Following AQP4 silencing in C6 cells, the increase in Cx43 expression was significantly attenuated (P<0.05). In normal cells, Cx43 silencing did not influence AQP4 expression (P>0.05). Therefore, it was hypothesized that AQP4 and Cx43 had two distinct mechanisms underlying brain edema formation within and surrounding the glioma. Cx43 may be a downstream effector of AQP4. The elucidation of this pathway may aid in the development of drugs targeting the interaction between AQP4 and Cx43, providing novel therapeutic possibilities for glioma-induced brain edema.

Endovascular treatment of severe acute basilar artery occlusion.

Severe acute basilar artery occlusion (BAO) has a high mortality rate but as yet no effective treatment has been developed. This study aimed to evaluate the feasibility and safety of combined mechanical thrombectomy, intra-arterial thrombolysis, and emergent stent placement for patients with severe acute BAO. Eighteen patients who were unconscious after confirmed onset of BAO and who were given arterial interventional treatment from March 2011 to June 2013 at our department were included in this study. The mean age was 59.56 years (range: 31-76 years) and patients were in a critical physical condition upon admission, and had a mean National Institutes of Health Stroke Scale (NIHSS) score of 25.94 (range: 18-35). All patients were treated with mechanical thrombectomy, 10 of whom received mechanical thrombectomy only. Of the others, eight were also treated with intra-arterial thrombolysis, three were treated with emergent stent placement, and 17 were treated with recanalization with an achieved recanalized rate of 94.4%. The average number of passes through the stent was 1.5 (range: 1-3) and five patients died (27.8%). Thirteen patients survived, and the mean NIHSS score was 6.54 (range: 0-16). Seven patients showed a modified Rankin Scale score ⩽ 2, and the rate of good prognoses was 38.9%. In the treatment of patients with severe acute BAO, intra-arterial mechanical thrombectomy combined with thrombolysis or stent placement are effective strategies to restore blood flow and preserve life, and these strategies have a low incidence of complications.

miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways.

Epidermal growth factor receptor (EGFR) signaling regulates glioblastoma cell proliferation, survival, migration and invasion and plays a key role in tumor progression. We show that microRNA-7 (miR-7) is a common regulator of the phosphoinositide-3-kinase (PI3K)/ATK and Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways, both of which are launched by EGFR through its two direct targets, the transcription factors PI3K and Raf-1, respectively. Enforced expression of miR-7 markedly decreased expression of PI3K, phosphorylated Akt, Raf-1, phosphorylated MEK 1/2, and cyclin D1, as well as slightly reduced expression of EGFR. Forced expression of PI3K or Raf-1 transcripts lacking the 3'-untranslated region (3'-UTR) partially reversed the effects of miR-7 on cell growth inhibition and cell cycle arrest in glioma cells. Additionally, transient expression of miR-7 in glioblastoma cells strongly inhibited in vivo glioblastoma xenograft growth. We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.

Mesenchymal stem cells show little tropism for the resting and differentiated cancer stem cell-like glioma cells.

Intrinsic resistance of glioma cells to radiation and chemotherapy is currently hypothesized to be partially attributed to the existence of cancer stem cells. Emerging studies suggest that mesenchymal stem cells may serve as a potential carrier for delivery of therapeutic genes to disseminated glioma cells. However, the tropism character of mesenchymal stem cells for cancer stem cell-like glioma cells has rarely been described. In this study, we obtained homologous bone marrow-derived (BM-) and adipose tissue-derived (AT-) mesenchymal stem cells (MSCs), fibroblast, and cancer stem cell-like glioma cells (CSGCs) from tumor-bearing mice, and compared the tropism character of BM- and AT-MSCs for CSGCs with various form of existence. To characterize the cell proliferation and differentiation, the spheroids of CSGCs were cultured on the surface of the substrate with different stiffness, combined with or withdrew basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in medium. Our results showed that the CSGCs during the process of cell proliferation, but not in resting and differentiated status, display strong tropism characteristics on both BM- and AT-MSCs, as well as the expression of their cell chemokine factors which mediate cell migration. If the conclusion is further confirmed, it may expose a fatal flaw of MSCs as tumor-targeted delivery of therapeutic agents in the treatment of the CSGCs, even other cancer stem cells, because there always exist a part of cancer stem cells that are in resting status. Overall, our findings provide novel insight into the complex issue of the MSCs as drug delivery in the treatment of brain tumors, especially in tumor stem cells.

Survivin, a key component of the Wnt/ß-catenin signaling pathway, contributes to traumatic brain injury-induced adult neurogenesis in the mouse dentate gyrus.

The enhancement of endogenous neurogenesis has been suggested in the treatment of traumatic brain injury (TBI); however, the factors that trigger the process of adult neurogenesis following TBI remain elusive. In the adult mammalian central nervous system, there are 2 neurogenic regions: the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricles, both of which maintain relatively quiescent states in a stable microenvironment. However, once stimulated by intrinsic and extrinsic events, relevant signals are activated in these 2 regions. In this study, in order to explore the mechanisms behind endogenous neurogenesis following TBI, we investigated potential factors regulating this process. We observed that the expression of survivin, an anti-apoptotic protein, increased in a time-dependent manner in the hippocampus in a mouse model of TBI. In addition, the number of survivin (+) cells, as well as that of BrdU (+) cells increased in the SGZ of the dentate gyrus (DG) in the hippocampus following TBI, as shown by immunofluorescence double staining; the co-localization of survivin and BrdU was shown in the merged images. The expression of survivin was also significantly increased in the doublecortin (DCX) (+) immature neurons in the DG of the hippocampus soon after the induction of TBI. Taken together, these data confirm the connection between the expression of survivin and adult neurogenesis following TBI; our data also suggest the therapeutic potential of upregulating survivin expression as a novel strategy for the effective treatment of TBI.

Poly(amido amine) is an ideal carrier of miR-7 for enhancing gene silencing effects on the EGFR pathway in U251 glioma cells.

microRNAs are regarded as promising drugs for glioma gene therapy. However, conventional administration routes, such as oral administration and intravenous infusion, present low efficiency due to the blood-brain barrier and intercellular retention, thereby limiting their application. Recent studies showed poly(amido amine) (PAMAM) was a candidate carrier due to its high solubilization, delayed release and low toxicity. In the present study, U251 human brain glioma cells were transfected with the miR-7 gene using PAMAM as the vector to determine the transfection efficiency and therapeutic effects in vivo and in vitro. We found that PAMAM exhibited higher transfection efficiency and longer duration of action compared with liposome delivery, and miR-7 efficiently silenced some genes involved in the epidermal growth factor receptor (EGFR) pathway and achieved favorable effects in treating glioma in vivo and in vitro. These investigations provide a basis for developing high-efficiency micromolecular drug delivery.