PNO1 promotes the progression of osteosarcoma via TGF-ß and YAP/TAZ pathway.

This study aimed to explore the potential role and mechanisms of the partner of NOB1 homolog (PNO1) in osteosarcoma. The expression of PNO1 in tumor and adjacent tissue samples was examined using western blotting. Lentiviral transfection was used to establish sh-Ctrl and sh-PNO1 osteosarcoma cell lines. MTT assay, Celigo cell cytometer count, and cell colony formation assay were used to investigate the proliferation of osteosarcoma cells in vitro, whereas xenotransplantation assay was performed for in vivo experiments. Wound-healing and Transwell assays were chosen to verify the migration and invasion of osteosarcoma cells. Flow cytometry assay and caspase-3/7 activity analysis were adopted for the analysis of cell apoptosis and cell cycle. Finally, transcriptome sequencing and bioinformatics analysis were adopted to explore the acting mechanisms. The expression of PNO1 was higher in osteosarcoma tissues than that in adjacent tissues. Down-regulation of PNO1 inhibited the proliferation, migration, and invasion, and induced cell apoptosis and cell cycle arrest of osteosarcoma cells. Furthermore, according to transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that PNO1 might affect the progression of osteosarcoma via TGF-ß and YAP/TAZ signaling pathways. PNO1 could be a potential target for osteosarcoma treatment.

Inverse relationship between femoral lateralization and neck-shaft angle is a joint event after intramedullary nailing of per trochanteric fractures.

This study explored the relationship between femoral lateralization and femoral neck-shaft angle after intramedullary nail (IM) fixation for per trochanteric fractures. 70 patients (AO/OTA 31A1-2) were investigated. Anteroposterior (AP) and lateral X-ray views pre- and post-operation were recorded. Patients were classified into three groups according to the position of the medial cortex of the head-neck fragment to that of the femoral shaft: being slightly superomedial (positive medial cortex support, PMCS), being smoothly contacted (neutral position, NP) or being displaced laterally (negative medial cortex support, NMCS). Patient demographics, femoral lateralization, and neck-shaft angle were measured and statistically analyzed pre- and post-operation. Functional recovery was evaluated by Harris score 3- and 6- months post-operation. All cases ultimately demonstrated radiographic fracture union. There was a tendency to have an increased neck-shaft angle (valgus alignment) in the PMCS group and increased femoral lateralization in the NP group (p < 0.05). Among those three groups, the change in femoral lateralization and neck-shaft angle was statistically different (p < 0.05). An inverse relationship between femoral lateralization and femoral neck-shaft angle was observed. Femoral lateralization increased correspondingly when the neck-shaft angle continuously decreased from the PMCS group to the NP group and then to the NMCS group, and patients in the PMCS group had better functional recovery than the other two groups (p < 0.05). Femoral lateralization was commonly produced after IM fixation for per trochanteric fractures. The fracture fixed in PMCS mode possesses the slightest change in femoral lateralization while maintaining valgus alignment of the femoral neck-shaft angle and good functional outcome, which is superior to NP or NMCS mode.

7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection.

BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.

Microbially induced calcium precipitation based simultaneous removal of fluoride, nitrate, and calcium by Pseudomonas sp. WZ39: Mechanisms and nucleation pathways.

A simultaneous denitrifying and mineralizing bacterium, Pseudomonas sp. WZ39 was isolated for fluoride (F-), nitrate (NO3--N), and calcium (Ca2+) removal. Strain WZ39 exhibited a remarkable defluoridation efficiency of 87.49% under a pH of 6.90, F- and Ca2+ concentration of 1.99 and 201.88 mg L-1, respectively. EEM, SEM-EDS, XRD, and FTIR analyses elucidated the chemical adsorption and co-precipitation with calcium salt contributed to the removal of F-. The mechanisms of biomineralization were also investigated by determining the role of bound and unbound extracellular polymeric substances (EPS), cell wall, and calcium channel in nucleation. The results showed that bacteria can promote nucleation on the templates of cell walls or EPS through the electrostatic effect. The presence of the calcium channel blocker inhibited the transport of intracellular Ca2+ to the extracellular environment. The outcome of the present research can provide a theoretical basis for the understanding of MICP phenomenon and the efficient treatment of F- containing groundwater.

Identification of Prognostic RBPs in Osteosarcoma.

Osteosarcoma often occurs in children and adolescents and causes poor prognosis. The role of RNA-binding proteins (RBPs) in malignant tumors has been elucidated in recent years. Our study aims to identify key RBPs in osteosarcoma that could be prognostic factors and treatment targets. GSE33382 dataset was downloaded from Gene Expression Omnibus (GEO) database. RBPs extraction and differential expression analysis was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological function of differential expression RBPs. Moreover, we constructed Protein-protein interaction (PPI) network and obtained key modules. Key RBPs were identified by univariate Cox regression analysis and multiple stepwise Cox regression analysis combined with the clinical information from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Risk score model was generated and validated by GSE16091 dataset. A total of 38 differential expression RBPs was identified. Go and KEGG results indicated these RBPs were significantly involved in ribosome biogenesis and mRNA surveillance pathway. COX regression analysis showed DDX24, DDX21, WARS and IGF2BP2 could be prognostic factors in osteosarcoma. Spearman's correlation analysis suggested that WARS might be important in osteosarcoma immune infiltration. In conclusion, DDX24, DDX21, WARS and IGF2BP2 might play key role in osteosarcoma, which could be therapuetic targets for osteosarcoma treatment.

Analysis of changes in the expression of Notch1 and HES1 and the prognosis of osteosarcoma patients following surgery.

The present study aimed to analyze the changes in the expression of Notch1 and hairy and enhancer of split-1 (HES1) and the prognosis of patients with osteosarcoma following surgery. Samples from 62 patients with osteosarcoma treated at Shandong Cancer hospital from April, 2011 to June, 2013 were collected as the research group, and those from 52 healthy individuals undergoing physical examination were collected as the control group. The expression levels of Notch1 and HES1 in the serum of patients with osteosarcoma were measured by ELISA before and after surgery. Pearson's correlation analysis was used to analyze the correlation between Notch1 expression and HES1 expression in the osteosarcoma patients. According to the expression levels of Notch1 and HES1, the patients were divided into the high expression group and the low expression group, and the 5-year survival rate of the patients was observed. The expression levels of Notch1 and HES1 in the osteosarcoma patients before surgery were higher than those after surgery (P<0.05). The sensitivity, specificity and AUC of Notch1 for osteosarcoma were 93.55%, 58.06% and 0.732 respectively, and those of HES1 were 82.26%, 61.29% and 0.766, respectively. The expression level of Notch1 positively correlated with the expression level of HES1 in the osteosarcoma patients (r=0.795, P<0.001). According to the expression levels of Notch1 and HES1, the patients were divided into the high and low expression groups. The survival rate of the low expression group was significantly higher than that of the high expression groups (P=0.045). Finally, multiple factors were analyzed by logistic regression, and it was found that tumor location, chemotherapy response, tumor size, Notch1 and HES1 were independent risk factors for prognosis. Notch1 and HES1 exhibited a low expression in patients following surgery. ROC curve analysis revealed that the two indicators had good diagnostic efficacy and were expected to become markers for diagnosis and prognosis of osteosarcoma.

Myricetin against myocardial injury in rat heat stroke model.

BACKGROUND: Heat stroke-induced mortality is rising across the globe. So, the design of prophylactic and/or therapeutic modalities for heat stroke is pressing need. The common plant derived flavonoid exhibits strong anti-oxidant and anti-inflammatory activities; however, its effects in heat stroke remain unknown. The study aimed to investigate the cardioprotective effects of myricetin on heat stroke induced acute myocardial injury as well as lethality in rats and to explore the underlying mechanisms. METHODS: Myocardial injury was induced by subjecting the anesthetized rats to a high ambient temperature of 43 °C for 70 min. An intragastrical dose of myricetin (5-25 mg/kg body weight) was given to rats once per day for one week prior to the start of heat stress. Heat shock protein 72 antibodies was given intraperitoneally to rats 24 h before the start of heat stress. Myocardial injury severity was estimated by determing myocardial damage scores, myocardial injury indicators, myocardial oxidative and inflammatory factors. Western blot analysis was used for cardiac expression of heat shock protein (HSP)72. RESULTS: Significant (P < 0.05) up-regulation of HSP-72 after chronic administration of myricetin coincided with significant (P < 0.05) reduction in hyperthermia, hypotension, cardiac inflammatory and oxidative damage and lethality. Inhibition of HSP-72 showed a significant (P < 0.05) reversal in the cardiaprotection as well as survival. CONCLUSIONS: Our results indicate that myricetin diminishes myocardial injury as well as lethality in heat stroke by up-regulating HSP-72 and show promise as a novel prevention therapeutic for heat stroke.

Spinal Cord Lateral Hemisection and Asymmetric Behavioral Assessments in Adult Rats.

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human Brown-Séquard syndrome is a common type of incomplete SCI caused by a lesion to one half of the spinal cord which results in paralysis and loss of proprioception on the same (or ipsilesional) side as the injury, and loss of pain and temperature sensation on the opposite (or contralesional) side. Adequate methodologies for producing a spinal cord lateral hemisection (HX) and assessing neurological impairments are essential to establish a reliable animal model of Brown-Séquard syndrome. Although lateral hemisection model plays a pivotal role in basic and translational research, standardized protocols for creating such a hemisection and assessing unilateralized function are lacking. The goal of this study is to describe step-by-step procedures to produce a rat spinal lateral HX at the 9th thoracic (T9) vertebral level. We, then, describe a combined behavior scale for HX (CBS-HX) that provides a simple and sensitive assessment of asymmetric neurological performance for unilateral SCI. The CBS-HX, ranging from 0 to 18, is composed of 4 individual assessments which include unilateral hindlimb stepping (UHS), coupling, contact placing, and grid walking. For CBS-HX, the ipsilateral and contralateral hindlimbs are assessed separately. We found that, after a T9 HX, the ipsilateral hindlimb showed impaired behavior function whereas the contralateral hindlimb showed substantial recovery. The CBS-HX effectively discriminated behavioral functions between ipsilateral and contralateral hindlimbs and detected temporal progression of recovery of the ipsilateral hindlimb. The CBS-HX components can be analyzed separately or in combination with other measures when needed. Although we only provided visual descriptions of the surgical procedures and behavioral assessments of a thoracic HX, the principle may be applied to other incomplete SCIs and at other levels of the injury.

Silencing METTL3 inhibits the proliferation and invasion of osteosarcoma by regulating ATAD2.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor in children and young adults. RNA N6-methyladenosine (m6A) is the most abundant internal modification in mammalian mRNA, which is involved in tumorigenesis and tumor progression. It has been reported that methyltransferase-like 3 (METTL3), the first reported m6A "writer", plays critical roles in cancer progression. However, its role and molecular mechanism in osteosarcoma is poor studied. In this study, we aimed to investigate the functional role and underlying mechanism of METTL3 in the progression of osteosarcoma. METHODS: We detected the mRNA expression of METTL3 in osteosarcoma cell lines, and immunofluorescence assay was performed to observe the location of METTL3. Cell lines with METTL3 gene overexpression or knockdown were established by pcDNA3.1-METTL3 or siRNA interferences in order to determine the function of METTL3 in osteosarcoma in vitro. Transcriptomic RNA sequencing (RNA-seq) were used to screen the target genes of METTL3 in osteosarcoma. RESULTS: We found that METTL3 localized in cytoplasm and nucleus of osteosarcoma cells. Silencing METTL3 in SAOS-2 and MG63 cells significantly inhibited the m6A methylation level, proliferation, migration, and invasion abilities, as well as promoted cell apoptosis. However, up-regulation of METTL3 had no significant effect on the biological behaviors of U2OS cells. Further mechanism analysis suggested that METTL3 knockdown inhibited the expression of ATPase family AAA domain containing 2 (ATAD2). Moreover, ATAD2 knockdown inhibited the proliferation and invasion of SAOS-2 and MG63 cells, while its overexpression showed a significant increase in cell proliferation and invasion. Furthermore, METTL3 knockdown abrogated the promoting effects of ATAD2 overexpression on osteosarcoma cells proliferation and invasion. CONCLUSION: Overall, our study revealed that METTL3 functions as an oncogene in the growth and invasion of osteosarcoma by regulating ATAD2, suggesting a potential therapeutic target for osteosarcoma treatment.

Imaging Neural Activity in the Primary Somatosensory Cortex Using Thy1-GCaMP6s Transgenic Mice.

The mammalian brain exhibits marked symmetry across the sagittal plane. However, detailed description of neural dynamics in symmetric brain regions in adult mammalian animals remains elusive. In this study, we describe an experimental procedure for measuring calcium dynamics through dual optical windows above bilateral primary somatosensory corticies (S1) in Thy1-GCaMP6s transgenic mice using 2-photon (2P) microscopy. This method enables recordings and quantifications of neural activity in bilateral mouse brain regions one at a time in the same experiment for a prolonged period in vivo. Key aspects of this method, which can be completed within an hour, include minimally invasive surgery procedures for creating dual optical windows, and the use of 2P imaging. Although we only demonstrate the technique in the S1 area, the method can be applied to other regions of the living brain facilitating the elucidation of structural and functional complexities of brain neural networks.

Melatonin provides protection against heat stroke-induced myocardial injury in male rats.

OBJECTIVES: This study aimed to investigate the cardioprotective effects of melatonin on heat stroke (HS) induced acute myocardial infarction in rats and to explore the underlying mechanisms. METHODS: Myocardial injury was induced by subjecting the anaesthetized rats to a high ambient temperature of 43°C for 70 min. Such a high ambient temperature caused hyperthermia, hypotension and myocardial injury in rats. Rats were treated with melatonin (3 mg/kg) intravenously one hour before and followed by an additional dose immediately after heat stress. KEY FINDINGS: At the onset of HS, animals displayed myocardial injury evidenced by increased levels of cardiac damage indicators (e.g. total lactate dehydrogenase, cardiac troponin I and creatine kinase-MB), increased cardiac damage scores and suppressed left ventricular performance. Animals with HS also had increased cardiac oxidative stress evidenced by increased levels of lipid peroxidation (e.g. increased thiobarbituric acid reactive substances) and decreased levels of antioxidant enzymes (e.g. superoxide dismutase, catalase and reduced glutathione) and activated inflammation (e.g. increased levels of interleukin-6 and tumour necrosis factor-α). Pretreatment with melatonin significantly reversed the HS-induced myocardial injury, cardiac oxidative stress and cardiac inflammation. CONCLUSIONS: Melatonin may protect against HS-induced myocardial injury in male rats by mitigating oxidative stress and inflammation.

Central projections and connections of lumbar primary afferent fibers in adult rats: effectively revealed using Texas red-dextran amine tracing.

Signals from lumbar primary afferent fibers are important for modulating locomotion of the hind-limbs. However, silver impregnation techniques, autoradiography, wheat germ agglutinin-horseradish peroxidase and cholera toxin B subunit-horseradish peroxidase cannot image the central projections and connections of the dorsal root in detail. Thus, we injected 3-kDa Texas red-dextran amine into the proximal trunks of L4 dorsal roots in adult rats. Confocal microscopy results revealed that numerous labeled arborizations and varicosities extended to the dorsal horn from T12-S4, to Clarke's column from T10-L2, and to the ventral horn from L1-5. The labeled varicosities at the L4 cord level were very dense, particularly in laminae I-III, and the density decreased gradually in more rostral and caudal segments. In addition, they were predominately distributed in laminae I-IV, moderately in laminae V-VII and sparsely in laminae VIII-X. Furthermore, direct contacts of lumbar afferent fibers with propriospinal neurons were widespread in gray matter. In conclusion, the projection and connection patterns of L4 afferents were illustrated in detail by Texas red-dextran amine-dorsal root tracing.

Is Limb Salvage With Microwave-induced Hyperthermia Better Than Amputation for Osteosarcoma of the Distal Tibia?

BACKGROUND: Amputation has been the standard surgical treatment for distal tibia osteosarcoma owing to its unique anatomic features. Preliminary research suggested that microwave-induced hyperthermia may have a role in treating osteosarcoma in some locations of the body (such as the pelvis), but to our knowledge, no comparative study has evaluated its efficacy in a difficult-to-treat location like the distal tibia. QUESTIONS: Does microwave-induced hyperthermia result in (1) improved survival, (2) decreased local recurrence, (3) improved Musculoskeletal Tumor Society (MSTS) scores, or (4) fewer complications than amputation in patients with a distal tibial osteosarcoma? METHODS: Between 2000 and 2015, we treated 79 patients for a distal tibia osteosarcoma without metastases. Of those, 52 were treated with microwave-induced hyperthermia, and 27 with amputation. Patients were considered eligible for microwave-induced hyperthermia if they had an at least 20-mm available distance from the tumor edge to the articular surface, good clinical and imaging response to neoadjuvant chemotherapy, and no pathologic fracture. Patients not meeting these indications were treated with amputation. In addition, if neither the posterior tibial artery nor the dorsalis pedis artery was salvageable, the patients were treated with amputation and were not included in any group in this study. A total of 13 other patients were treated with conventional limb-salvage resections and reconstructions (at the request of the patient, based on patient preference) and were not included in this study. All 79 patients in this retrospective study were available for followup at a minimum of 12 months (mean followup in the hyperthermia group, 79 months, range 12-158 months; mean followup in the amputation group, 95 months, range, 15-142 months). With the numbers available, the groups were no different in terms of sex, age, tumor grade, tumor stage, or tumor size. All statistical tests were two-sided, and a probability less than 0.05 was considered statistically significant. Survival to death was evaluated using Kaplan-Meier analysis. Complications were recorded from the patients' files and graded using the classification of surgical complications described by Dindo et al. RESULTS: In the limb-salvage group, Kaplan Meier survival at 6 years was 80% (95% CI, 63%-90%), and this was not different with the numbers available from survivorship in the amputation group at 6 years (70%; 95% CI, 37%-90%; p = 0.301).With the numbers available, we found no difference in local recurrence (six versus 0; p = 0.066). However mean ± SD MSTS functional scores were higher in patients who had microwave-induced hyperthermia compared with those who had amputations (85% ± 6% versus 66% ± 5%; p = 0.008).With the numbers available, we found no difference in the proportion of patients experiencing complications between the two groups (six of 52 [12%] versus three of 27 [11%]; p = 0.954). CONCLUSIONS: We were encouraged to find no early differences in survival, local recurrence, or serious complications between microwave-induced hyperthermia and amputation, and a functional advantage in favor of microwave-induced hyperthermia. However, these findings should be replicated in larger studies with longer mean duration of followup, and in studies that compare microwave-induced hyperthermia with conventional limb-sparing approaches. LEVEL OF EVIDENCE: Level III, therapeutic study.

Quercetin protects against heat stroke-induced myocardial injury in male rats: Antioxidative and antiinflammatory mechanisms.

Heat stroke is characterized by hyperthermia, systemic inflammation, and multiple organ failure including arterial hypotension. This definition can be fulfilled by a rat model of heat stroke used in the present study. Anesthetized animals were exposed to heat exposure (43 °C for 70 min) and then returned to room temperature (26 °C) for recovery. One hour before heat exposure, an intraperitoneal dose of quercetin (30 mg/kg) or vehicle (normal saline 1 ml/kg) was administered to the experimental groups of rats. Additional injection was administered immediately after the onset of heat stroke. Immediately after the onset of heat stroke. Vehicle-treated rats displayed (i) hyperthermia; (ii) suppressed left ventricular function; (iii) decreased contents of cardiac total antioxiant capacity (e.g., superoxide dismutase, glutathione peroxidase, catalase); (iv) increased contents of cardiac oxidative capacity malondialdehyde and thiobarbituric acid reactive substances; (v) increased cardiac levels of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6; and (vi) decreased cardiac levels of an anti-inflammatory cytokine interleukin 10. Histopathologic and survival observation provided supportive evidence for biochemical analyses. These heat stroke reactions all can be significantly attenuated by quercetin therapy. Our data suggest that quercetin therapy might improve outcomes of heat stroke in rats by attenuating excessive hyperthermia as well as myocardial injury. The protective effects of quercetin could be attributed to anti-lipid peroxidative, anti-oxidant, and anti-inflammatory properties.

Inhibitory Effect of Endomorphin-2 Binding to the µ-Opioid Receptor in the Rat Pre-Bötzinger Complex on the Breathing Activity.

Opiates are commonly used analgesics that often cause clinical respiratory depression. However, their underlying mechanisms remain unclear. Endomorphin-2 (EM2) is a novel, endogenous tetrapeptide opioid with very high affinity and selectivity for the µ-opioid receptor (MOR). The pre-Bötzinger complex (pre-BötC) is considered the center of respiratory rhythm generation, and the synaptic connections in this region are essential for respiratory rhythm. The present study identified EM2-like immunoreactive (LI) axonal terminals in the pre-BötC of adult rats. Some EM2-LI axonal terminals made principally symmetric synapses with neurokinin 1 receptor (NK1R)-LI or MOR-LI neuronal dendritic processes in the pre-BötC. Unilateral microinjection of EM2 into the pre-BötC decreased breathing frequency and amplitude. A prior microinjection of the selective MOR antagonist ß-funaltrexamine (ß-FNA) into the pre-BötC prevented the effects of EM2. The present results suggest that EM2-LI axonal terminals modulate NK1R-expressing neurons in the pre-BötC and that EM2 plays a role in respiratory depression through MORs in the pre-BötC.

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia.

Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund's Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a "crosstalk" between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.

Transplantation of Pro-Oligodendroblasts, Preconditioned by LPS-Stimulated Microglia, Promotes Recovery After Acute Contusive Spinal Cord Injury.

Spinal cord injury (SCI) is a significant clinical challenge, and to date no effective treatment is available. Oligodendrocyte progenitor cell (OPC) transplantation has been a promising strategy for SCI repair. However, the poor posttransplantation survival and deficiency in differentiation into myelinating oligodendrocytes (OLs) are two major challenges that limit the use of OPCs as donor cells. Here we report the generation of an OL lineage population [i.e., pro-oligodendroblasts (proOLs)] that is relatively more mature than OPCs for transplantation after SCI. We found that proOLs responded to lipopolysaccharide (LPS)-stimulated microglia conditioned medium (L+M) by preserving toll-like receptor 4 (TLR4) expression, improving cell viability, and enhancing the expression of a myelinating OL marker myelin basic protein (MBP), compared to other OL lineage cells exposed to either LPS-stimulated (L+M) or nonstimulated microglia conditioned medium (LM). When L+M-stimulated proOLs were intrathecally delivered through a lumbar puncture after a T10 thoracic contusive SCI, they promoted behavioral recovery, as assessed by the BassoBeattieBresnahan (BBB) locomotor rating scale, stride length, and slips on the grid tests. Histologically, transplantation of L+M proOLs caused a considerable increase in intralesional axon numbers and myelination, and less accumulation of invading macrophages when compared with the vehicle control or OPC transplantation. Thus, transplantation of proOLs, preconditioned by L+M, may offer a better therapeutic potential for SCI than OPCs since the former may have initiated the differentiation process toward OLs prior to transplantation.

Bull serum albumin coated Au@Agnanorods as SERS probes for ultrasensitive osteosarcoma cell detection.

Surface-Enhanced Raman scattering (SERS) has been widely used for imaging and sensing. However, limited reports are currently available on SERS-based cancer cell targeting strategy due to the challenge of synthesizing highly sensitive, reproducible and biocompatible SERS probe. Herein, we developed novel SERS probes, based on BSA (Bull Serum Albumin) coated gold-silver core-shell nanorods modified with Raman reporter 5,5-dithiobis 2-nitrobenzoic acid (DTNB) (Au@AgNRs@BSA@Anti-MICA), for in vitro cancer cell detection. Our results demonstrate that the SERS probe is very robust for cancer cell ultrasensitive detection with good biocompatibility and strong SERS signal.

MiR-125b Functions as a Tumor Suppressor and Enhances Chemosensitivity to Cisplatin in Osteosarcoma.

MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. To date, the potential microRNAs regulating the growth and progression of osteosarcoma are not fully identified yet. Previous reports have shown differentially expressed miR-125b in osteosarcoma. However, the role of miR-125b in human osteosarcoma has not been totally illuminated. In this study, we have shown that miR-125b was downregulated in human osteosarcoma tissues compared to the adjacent tissues and effects as a tumor suppressor in vitro We found that stable overexpression of miR-125b in osteosarcoma cell lines U2OS and MG-63 inhibited cell proliferation, migration, and invasion. Our data also verified that Bcl-2 is the target of miR-125b. Meanwhile, we showed that Bcl-2 was inversely correlated with miR-125b in osteosarcoma tissues. More importantly, we proved that miR-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting Bcl-2. In conclusion, our data demonstrate that miR-125b is a tumor suppressor and support its potential application for the treatment of osteosarcoma in the future.

Correlation of GLUT9 Polymorphisms With Gout Risk.

Single nucleotide polymorphisms (SNPs) at the glucose transporter 9 (GLUT9) locus are clearly related to uric acid concentrations previously identified as a major cause of gout. Due to the important function of various SNPs, we hypothesized that the common GLUT9 polymorphisms (rs16890979, rs6855911, and rs7442295) are associated with gout risk. The purpose of this investigation was to test the hypothesis.Gout risk was estimated by calculating odds ratios and 95% confidence intervals (ORs and 95% CIs). Either the fixed- or the random-effect model was used for OR calculations. Subgroup analyses were carried out by ethnicity for rs16890979 and by gender for all SNPs.We analyzed a total of 8 studies involving 2525 subjects for rs16890979, 2654 for rs6855911, and 2637 for rs7442295. A significantly declined risk was suggested in the meta-analyses of rs16890979 under dominant model (OR = 0.44, 95% CI = 0.34-0.58) and heterozygote model (OR = 0.44, 95% CI = 0.33-0.59). The OR was 0.41 under allele frequency model (OR = 0.41, 95% CI = 0.33-0.53). Significantly declined risk in relation to rs16890979 was also found among Asians. Similarly decreased risk was revealed for rs7442295, both in total samples and in males. However, the meta-analysis of rs6855911 revealed no significant associations.These data seem to support the hypothesis that the risk of gout may be associated with GLUT9 rs16890979 and rs7442295.