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Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.

Neuropathic pain (NP) affects countless people worldwide, but there is no effective treatment. Histone deacetylases (HDACs) participate in epigenetic modifications, which are involved in neuropathy-induced nociceptive sensitization. Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter that can inhibit NP. HDACs regulate glutamic acid decarboxylase (GAD) 65 and the production of its downstream metabolite GABA. However, the role of HDACs and their possible cellular mechanisms in the spinal cord in neuropathy remains unclear. We found Hdac3, Hdac4, and Hdac6 gene upregulation in the lumbar spinal cord dorsal horn (SCDH) in chronic constriction injury (CCI) rats by RT-qPCR analysis. By western blotting and immunofluorescence staining, we further confirmed that the HDAC3, HDAC4, and HDAC6 proteins were significantly upregulated, and GAD65 and GABA production decreased dramatically. Intrathecal administration of panobinostat, a non-selective HDAC inhibitor, attenuated nociceptive behavior (thermal hyperalgesia and mechanical allodynia) and restored to downregulated spinal GAD65 and GABA in CCI rats. Thus, the upregulation of HDAC expression might induce nociception through GAD65 and GABA inhibition in CCI-induced neuropathy. These findings strongly suggest that HDACs regulate inhibitory neurotransmitters as a potential therapeutic strategy for an epigenetic approach to managing NP.

Background: Osteoarthritis (OA) is the most common form of joint disorder and arthritis worldwide. Joint pain and dysfunction are associated with this multifactorial disease characterized by the gradual degeneration of articular cartilage. The metabolic reprogramming of osteoarthritic chondrocytes to glycolysis instead of oxidative phosphorylation results in reduced ATP and lactate accumulation. When the glycolytic metabolite pyruvate is converted into lactate by lactate dehydrogenase A (LDHA), cartilage degeneration occurs. In the present study, we examined the chondroprotective effects of the LDHA inhibitor, oxamate on experimental OA rats. Methods: Anterior cruciate ligament transection (ACLT)-induced ACLT-rats received an intraarticular (IA) injection of oxamate once a week for 5 weeks from the 10th to 14th after surgery. Animals were divided into four groups as follows: Sham, ACLT, ACLT + oxamate (0.25mg/kg), and ACLT + oxamate (2.5mg/kg). The results showed that an IA injection of oxamate significantly reduced weight-bearing defects and knee swelling in ACLT-rats. Results: Histopathological analyses showed that oxamate caused significantly less cartilage degeneration than ACLT alone. Moreover, IA oxamate exerts hypertrophic effects in the chondrocyte of articular cartilage by inhibiting glucose-transporter 1, glucose-transporter 3, pyruvate kinase, LDHA, pyruvate dehydrogenase kinase 1, and pyruvate dehydrogenase kinase 2. Terminal deoxynucleotidyl transferase dUTP nick end labeling revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Conclusions: We propose that oxamate is beneficial for patients with OA and is associated with regulating glycolysis-related protein expression. In future clinical applications, our findings will provide new insights of LHDA inhibitor, oxamate into delaying strategies for OA progression.

Background Microelectrode recording (MER)-guided deep brain stimulation (DBS) remains the standard electrophysiological procedure to place the DBS lead at the optimal target. When single-track MER or test stimulation yields suboptimal results, trajectory adjustments are needed. Intraoperative computed tomography (iCT) can be useful to visualize the microelectrode and verify possible adjustments. The aim of this study was to evaluate the effect of iCT in MER during frameless stereotactic DBS for Parkinson disease (PD). Methods We retrospectively collected 28 PD patients, of whom 19 received iCT and 9 did not, and measured intracranial volume, cerebral volume, cerebrospinal fluid volume, and pneumocephalus volume. Euclidean distance was assessed according to merged preoperative brain CT and magnetic resonance imaging and postoperative brain CT. Results Fifty-six hemispheres in the 28 patients were analyzed for MER tracks. The patients who received iCT had a significantly lower mean number of MER tracks (1.6 vs. 2.6, P = 0.013) and lower mean Euclidean distance (2.2 mm vs. 2.7 mm, P = 0.033) compared with those who did not receive iCT. Although there was a trend of a decrease in pneumocephalus using intraoperative imaging, there was no significant difference in surgical time. Conclusions iCT can reduce the number of MER tracks and increase surgical accuracy. Further studies are warranted to investigate whether iCT can reduce surgical complications and improve surgical outcomes.

Parkinson’s disease (PD) is one of the most widespread neurodegenerative diseases. However, the currently available treatments could only relieve symptoms. Novel therapeutic targets are urgently needed. Several previous studies mentioned that protein tyrosine phosphatase 1B (PTP1B) acted as a negative regulator of the insulin signal pathway and played a significant role in the inflammation process. However, few studies have investigated the role of PTP1B in the central nervous system. Our study showed that suramin, an inhibitor of PTP1B, could improve neuronal damage. It could significantly attenuate the interferon-gamma-induced upregulation of proinflammatory cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). It enhanced M2 type microglia markers, such as arginase-1 and Ym-1 in BV2 murine microglial cells. PTP1B inhibition also reversed 6-hydroxydopamine- (6-OHDA-) induced downregulation of phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. Besides, we knocked down and overexpressed PTP1B in the SH-SY5Y cells to confirm its role in neuroprotection. We also verified the effect of suramin in the zebrafish PD model. Treatment with suramin could significantly reverse 6-OHDA-induced locomotor deficits and improved tyrosine hydroxylase (TH) via attenuating endoplasmic reticulum (ER) stress biomarkers. These results support that PTP1B could potentially regulate PD via antineuroinflammation and antiapoptotic pathways.

Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live‐cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases‐2 and ‐9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell‐mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal‐regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments., We first describe the anti‐cancer activities of the antimicrobial peptide tilapia piscidin 3 which inhibits infiltration and motility of glioblastoma multiforme cells.

Osteosarcoma (OSA) is the most common type of cancer that originates in the bone and usually occurs in young children. OSA patients were treated with neoadjuvant chemotherapy and surgery, and the results were disappointing. Marine antimicrobial peptides (AMPs) have been the focus of antibiotic research because they are resistant to pathogen infection. Piscidin-1 is an AMP from the hybrid striped bass (Morone saxatilis × M. chrysops) and has approximately 22 amino acids. Research has shown that piscidin-1 can inhibit bacterial infections and has antinociception and anti-cancer properties; however, the regulatory effects of piscidin-1 on mitochondrial dysfunction in cancer cells are still unknown. We aimed to identify the effects of piscidin-1 on mitochondrial reactive oxygen species (mtROS) and apoptosis in OSA cells. Our analyses indicated that piscidin-1 has more cytotoxic effects against OSA cells than against lung and ovarian cancer cells; however, it has no effect on non-cancer cells. Piscidin-1 induces apoptosis in OSA cells, regulates mtROS, reduces mitochondrial antioxidant manganese superoxide dismutase and mitochondrial transmembrane potential, and decreases adenosine 5′-triphosphate production, thus leading to mitochondrial dysfunction and apoptosis. The mitochondrial antioxidant, mitoTempo, reduces the apoptosis induced by piscidin-1. Results suggest that piscidin-1 has potential for use in OSA treatment.

Background Angiogenesis in the central nervous system is visible in animal models of neuroinflammation and bone cancer pain. However, whether spinal angiogenesis exists and contributes to central sensitization in neuropathic pain remains unclear. This study analyzed the impact of angiogenesis on spinal neuroinflammation in neuropathic pain. Methods Rats with chronic constriction injury (CCI) to sciatic nerve underwent implantation of an intrathecal catheter. Fumagillin or vascular endothelial growth factor-A antibody (anti-VEGF-A) was administered intrathecally. Nociceptive behaviors, cytokine immunoassay, Western blot, and immunohistochemical analysis assessed the effect of angiogenesis inhibition on CCI-induced neuropathic pain. Results VEGF, cluster of differentiation 31 (CD31), and von Willebrand factor (vWF) expressions increased after CCI in the ipsilateral lumbar spinal cord compared to that in the contralateral side of CCI and control rats from postoperative day (POD) 7 to 28, with a peak at POD 14. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 concentrations, but not IL-10 levels, also increased in the ipsilateral spinal cord after CCI. Fumagillin and anti-VEGF-A reduced CCI-induced thermal hyperalgesia from POD 5 to 14 and mechanical allodynia from POD 3 to 14. Fumagillin reduced CCI-upregulated expressions of angiogenic factors and astrocytes. Furthermore, fumagillin decreased TNF-α and IL-6 amounts and increased IL-10 levels at POD 7 and 14, but not IL-1β concentrations. Conclusions Fumagillin significantly ameliorates CCI-induced nociceptive sensitization, spinal angiogenesis and astrocyte activation. Our results suggest that angiogenesis inhibitor treatment suppresses peripheral neuropathy-induced central angiogenesis, neuroinflammation, astrocyte activation, and neuropathic pain.

Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains &lt, 30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM.

Osteoarthritis (OA) is the most common articular degenerative disease characterized by chronic pain, joint inflammation, and movement limitations, which are significantly influenced by aberrant epigenetic modifications of numerous OA-susceptible genes. Recent studies revealed that both the abnormal activation and differential expression of histone deacetylases (HDACs) might contribute to OA pathogenesis. In this study, we investigated the chondroprotective effects of a marine-derived HDAC inhibitor, panobinostat, on anterior cruciate ligament transection (ACLT)-induced experimental OA rats. The intra-articular administration of 2 or 10 µg of panobinostat (each group, n = 7) per week from the 6th to 17th week attenuates ACLT-induced nociceptive behaviors, including secondary mechanical allodynia and weight-bearing distribution. Histopathological and microcomputed tomography analysis showed that panobinostat significantly prevents cartilage degeneration after ACLT. Moreover, intra-articular panobinostat exerts hypertrophic effects in the chondrocytes of articular cartilage by regulating the protein expressions of HDAC4, HDAC6, HDAC7, runt-domain transcription factor-2, and matrix metalloproteinase-13. The study indicated that HDACs might have different modulations on the chondrocyte phenotype in the early stages of OA development. These results provide new evidence that panobinostat may be a potential therapeutic drug for OA.

Background Bladder cancer (BC) is a very common type of malignant cancer in men and new therapeutic strategies are urgently needed to reduce mortality. Several studies have demonstrated that Rhopaloic acid A (RA), a compound isolated from marine sponges, fights cancer but its potential anti-tumor effect on BC is still unknown. Purpose The present study was aimed to explore the potential anti-tumor effects of RA against human BC cells and the underlying molecular mechanism. Methods Cell cytotoxicity was determined using the MTT and colony formation assays. Cell cycle distribution, apoptosis induction and generation of mitochondrial reactive oxygen species (ROS) were analyzed by flow cytometry. Mitochondrial membrane potential, acridine orange staining and intracellular ROS levels were observed using fluorescence microscopy. Levels of various signaling proteins were assessed using Western blotting. Furthermore, a zebrafish BC xenotransplantation model was used to confirm the anti-tumor effect of RA in vivo. Results Treatment with RA significantly suppressed the proliferation of BC cells that resulted from G2/M cycle arrest. Additionally, RA induced mitochondrial-mediated apoptosis and autophagy in BC cells. The death of BC cells induced by RA was rescued by treatment with inhibitors of apoptosis (Z-VAD-FMA) or autophagy (3-MA). RA activated the MAPK pathway and increased the production of cellular and mitochondrial ROS. Treatment with the ROS scavenger N-acetyl cysteine, effectively reversed the induction of apoptosis, autophagy, JNK activation and DNA damage elicited by RA. Finally, RA significantly inhibited tumor growth in a zebrafish BC xenotransplantation model. Conclusion Taken together, our findings indicate that RA induces apoptosis and autophagy and activates the MAPK pathway through ROS-mediated signaling in human BC cells. This RA-induced pathway offers insights into the molecular mechanism of its antitumor effect and shows that RA is a promising candidate for the treatment of BC.

Background Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. Method OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-β) and nerve growth factor (NGF) in articular cartilage chondrocytes. Results OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-β expression, in OA-affected cartilage. Conclusions Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-β expression. Significance Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-β expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.

A new eunicellin diterpenoid, cladieunicellin U (1), along with a new natural eunicellin, cladieunicellin V (2), and two known analogues, sclerophytins A (3) and B (4), were obtained from an octocoral identified as Cladiella sp. The structures, including the absolute configurations, of eunicellins 1–4 were elucidated by using spectroscopic methods and compared with the spectroscopic and physical data reported in the literature. Eunicellins 1, 3 and 4 decreased the release of elastase, while eunicellins 2 and 4 showed inhibitory effects in terms of the generation of superoxide anions by human neutrophils. Eunicellins 1 and 4 were found to show moderate cytotoxicity toward the leukemia K562 cells (IC50 = 12.8, 11.4 μg/mL, respectively) and 2 exhibited moderate cytotoxicity toward the leukemia MOLT-4 cells (IC50 = 18.8 μg/mL).

Cranioplasty can improve a patient's psychosocial and cognitive functions after decompressive craniectomy, however seizures are a common complication after cranioplasty. The risk factors for early and late seizures after cranioplasty are unclear. This study is to evaluate the risk factors for early and late seizure after cranioplasty.Two hundred and thirty-eight patients who received cranioplasty following craniectomy between January 2012 and December 2014 were included in this study. The risk factors of the patients with early and late post-cranioplasty seizures were compared to those with no post-cranioplasty seizures.Seizures (73/238, 30.3%) were the most common complication after cranioplasty. Of these 73 patients, 17 (7.1%) had early post-cranioplasty seizures and 56 (23.5%) had late post-cranioplasty seizures. Early post-cranioplasty seizures were related to a longer interval between craniectomy and cranioplasty (P = 0.006), artificial materials (P 0.001), and patients with late post-craniectomy seizures (P = 0.001). Late post-cranioplasty seizures were related to the presence of neurological deficits (P = 0.042). After stepwise logistic regression analysis, a longer interval between craniectomy and cranioplasty (P = 0.012; OR: 1.004, 95% CI: 1.001-1.007) and late post-craniectomy seizures (P = 0.033; OR: 4.335, 95% CI: 1.127-16.675) were independently associated with early post-cranioplasty seizures.Delayed cranioplasty procedures and seizures before cranioplasty were significantly associated with early post-cranioplasty seizures. Further studies are warranted to investigate whether early surgery after craniectomy can reduce the risk of early post-cranioplasty seizures.

Microglia-related neuroinflammation is associated with a variety of neurodegenerative diseases. Flavonoids have demonstrated different pharmacological effects, such as antioxidation, neuroprotection and anti-inflammation However, the effect of flavonoid 6-methoxyflavone (6-MeOF) on microglia-mediated neuroinflammation remain unknown.The current study aim to study the antineuroinflammatory effects of 6-MeOF in lipopolysaccharide- (LPS-) induced microglia in vitro and in vivo.Pretreatment of BV2 microglia cells with 6-MeOF for 1 h then stimulated with LPS (100 ng/ml) for 24 h. The expression levels of pro-inflammatory factors, NO and reactive oxygen species (ROS) were performed by the enzyme-linked immunosorbent assay (ELISA), Griess assay and flow cytometry. Western blotting was used to assess MAPK, NF-κB signal transducer and antioxidant enzymes-related proteins. Analysis of ROS and microglial morphology was confirmed in the zebrafish and mice brain, respectively.Our results demonstrated that 6-MeOF dose-dependently prevent cell death and decreased the levels of pro-inflammatory mediators in LPS-stimulated BV2 microglia cells. Phosphorylated NF-κB/IκB and TLR4/MyD88/p38 MAPK/JNK proteins after exposure to 6-MeOF was suppressed in LPS-activated BV-2 microglial cells. 6-MeOF also presented antioxidant activity by reduction of NO, ROS, iNOS and COX-2 and the induction of the level of HO-1 and NQO1 expressions in LPS-activated BV2 microglial cells. Furthermore, we demonstrated that 6-MeOF inhibited LPS-induced NO generation in an experimental zebrafish model and prevent the LPS-induced microgliosis in the prefrontal cortex and substantia nigra of mice.These results explored that 6-MeOF possesses potential as anti-inflammatory and anti-oxidant agents against microglia-associated neuroinflammatory disorders.

Intracranial hemorrhage from stroke and head trauma elicits a cascade of inflammatory and immune reactions detrimental to neurological integrity and function at cellular and molecular levels. This study tested the hypothesis that human umbilical cord–derived mesenchymal stem cell (HUCDMSC) therapy effectively protected the brain integrity and neurological function in rat after acute traumatic brain injury (TBI). Adult male Sprague-Dawley rats ( n = 30) were equally divided into group 1 (sham-operated control), group 2 (TBI), and group 3 [TBI + HUCDMSC (1.2 × 106 cells/intravenous injection at 3 h after TBI)] and euthanized by day 28 after TBI procedure. The results of corner test and inclined plane test showed the neurological function was significantly progressively improved from days 3, 7, 14, and 28 in groups 1 and 3 than in group 2, and group 1 than in group 3 (all P < 0.001). By day 28, brain magnetic resonance imaging brain ischemic volume was significantly increased in group 2 than in group 3 ( P < 0.001). The protein expressions of apoptosis [mitochondrial-bax positive cells (Bax)/cleaved-caspase3/cleaved-poly(adenosine diphosphate (ADP)-ribose) polymerase], fibrosis (Smad3 positive cells (Smad3)/transforming growth factor-β), oxidative stress (NADPH Oxidase 1 (NOX-1)/NADPH Oxidase 2 (NOX-2)/oxidized-protein/cytochrome b-245 alpha chain (p22phox)), and brain-edema/deoxyribonucleic acid (DNA)–damaged biomarkers (Aquaporin-4/gamma H2A histone family member X ( (γ-H2AX)) displayed an identical pattern to neurological function among the three groups (all P < 0.0001), whereas the protein expressions of angiogenesis biomarkers (vascular endothelial growth factor/stromal cell–derived factor-1α/C-X-C chemokine receptor type 4 (CXCR4)) significantly increased from groups 1 to 3 (all P < 0.0001). The cellular expressions of inflammatory biomarkers (cluster of differentiation 14 (+) cells (CD14+)/glial fibrillary acidic protein positive cells (GFAP+)/ a member of a new family of EGF-TM7 molecules positive cells (F4/80+)) and DNA-damaged parameter (γ-H2AX) exhibited an identical pattern, whereas cellular expressions of neural integrity (hexaribonucleotide Binding Protein-3 positive cells (NeuN+)/nestin+/doublecortin+) exhibited an opposite pattern of neurological function among the three groups (all P < 0.0001). Xenogeneic HUCDMSC therapy was safe and it significantly preserved neurological function and brain architecture in rat after TBI.

MINI: In this study, respiratory function at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical spinal cord injury. Serum thiobarbituric acid-reactive substances level at admission can be a useful predictor for severity in acute cervical patients with spinal cord injury.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study.We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI.Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI.Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared.The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%).In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients.3.Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study. We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI. Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI. Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared. The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 μmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 μmol/L (sensitivity 100% and specificity 90.0%). In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients. Level of Evidence: 3.

Supplementary_Table_1 for Human Umbilical Cord–Derived Mesenchymal Stem Cell Therapy Effectively Protected the Brain Architecture and Neurological Function in Rat After Acute Traumatic Brain Injury by Kuan-Hung Chen, Pei-Lin Shao, Yi-Chen Li, John Y. Chiang, Pei-Hsun Sung, Hui-Wen Chien, Fu-Yuan Shih, Mel S. Lee, Wu-Fu Chen and Hon-Kan Yip in Cell Transplantation

The proliferation of drug-resistant pathogens continues to increase, giving rise to serious public health concerns. Many researchers have formulated metal oxide nanoparticles for use as novel antibacterial agents. In the present study, copper oxide (CuO) was synthesized by simple hydrothermal synthesis, and doping was performed to introduce different polymers onto the NP surface for bacteriostasis optimization. The polymer-modified CuO NPs were analyzed further with XRD, FTIR, TEM, DLS and zeta potential to study their morphology, size, and the charge of the substrate. The results indicate that polymer-modified CuO NPs had a significantly higher bacteriostatic rate than unmodified CuO NPs. In particular, polydopamine (PDA)-modified CuO (CuO-PDA) NPs, which carry a weakly negative surface charge, exhibited excellent antibacterial effects, with a bacteriostatic rate of up to 85.8 ± 0.2% within 3 h. When compared to other polymer-modified CuO NPs, CuO-PDA NPs exhibited superior bacteriostatic activity due to their smaller size, surface charge, and favorable van der Waals interactions. This may be attributed to the fact that the CuO-PDA NPs had relatively lipophilic structures at pH 7.4, which increased their affinity for the lipopolysaccharide-containing outer membrane of the Gram-negative bacterium Escherichia coli.

// Chun-Ting Liu 1, * , Bei-Yu Wu 1, * , Yu-Chiang Hung 1, 2, * , Lin-Yi Wang 3 , Yan-Yuh Lee 3 , Tsu-Kung Lin 4 , Pao-Yen Lin 5 , Wu-Fu Chen 6 , Jen-Huai Chiang 7, 8 , Sheng-Feng Hsu 9, 10 and Wen-Long Hu 1, 11, 12, * 1 Department of Chinese Medicine, Kaohsiung Chang Gung Memorial Hospital and School of Traditional Chinese Medicine, Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 School of Chinese Medicine for Post Baccalaureate, I-Shou University, Kaohsiung, Taiwan 3 Department of Physical Medicine and Rehabilitation, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 4 Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 6 Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 7 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan 8 College of Medicine, China Medical University, Taichung, Taiwan 9 Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan 10 Department of Chinese Medicine, China Medical University Hospital, Taipei Branch, Taipei, Taiwan 11 Kaohsiung Medical University College of Medicine, Kaohsiung, Taiwan 12 Fooyin University College of Nursing, Kaohsiung, Taiwan * These authors contributed equally to this work Correspondence to: Wen-Long Hu, email: oolonghu@gmail.com Keywords: dementia, migraine, pharmaco-epidemiology, national health insurance research database, Chinese herbal product Received: February 27, 2017 Accepted: June 28, 2017 Published: July 08, 2017 ABSTRACT Patients with migraine are reportedly at increased risk of developing dementia. We aimed to investigate the association between traditional Chinese medicine (TCM) use and dementia risk in migraine patients. This longitudinal cohort study used the Taiwanese National Health Insurance Research Database to identify 32,386 diagnosed migraine patients aged 20 years and above who received treatment from 1997 to 2010. To balance comparability between TCM users and non-TCM users, we randomly selected equal numbers from each group, and compared subgroups compiled based on combinations of age, sex, index year, and year of migraine diagnosis. All enrollees received follow-up until the end of 2013 to measure dementia incidence. We identified 1,402 TCM users and non-TCM users after frequency matching. A total of 134 subjects were newly diagnosed with dementia during the follow-up period. TCM users were significantly less likely to develop dementia than non-TCM users. The most frequently prescribed formulae and single Chinese herbal products were Jia-Wei-Xiao-Yao-San and Yan-Hu-Suo, respectively. This population-based study revealed a decreased dementia risk in migraine patients with TCM use. These findings may provide a reference for dementia prevention strategies, and help integrate TCM into clinical intervention programs that provide a favorable prognosis for migraine patients.

SummaryAims We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats. Methods The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies. Results IL-1β increased phosphorylation of NR-1 (p-NR1) subunit of N-methyl-D-aspartate receptors in neurons and microglia, reduced glutamate transporters (GTs; glutamate/aspartate transporter by 60.9%, glutamate transporter-1 by 55.0%, excitatory amino acid carrier-1 by 39.8%; P

Two new 11,20-epoxybriaranes, fragilides P (1) and Q (2), as well as two known analogues, robustolide F (3) and juncin Z (4), were obtained from the gorgonian coral Junceella fragilis. The structures, including the absolute configurations of briaranes 1 and 2, were elucidated by using spectroscopic methods and comparing the spectroscopic and rotation data with those of known related analogues. Briarane 4 decreased the generation of superoxide anions by human neutrophils. The propionate group in 1 is rarely found.

Pharmaceutical agents for halting the progression of Parkinson&rsquo, s disease (PD) are lacking. The current available medications only relieve clinical symptoms and may cause severe side effects. Therefore, there is an urgent need for novel drug candidates for PD. In this study, we demonstrated the neuroprotective activity of stellettin B (SB), a compound isolated from marine sponges. We showed that SB could significantly protect SH-SY5Y cells against 6-OHDA-induced cellular damage by inhibiting cell apoptosis and oxidative stress through PI3K/Akt, MAPK, caspase cascade modulation and Nrf2/HO-1 cascade modulation, respectively. In addition, an in vivo study showed that SB reversed 6-OHDA-induced a locomotor deficit in a zebrafish model of PD. The potential for developing SB as a candidate drug for PD treatment is discussed.

Angiogenesis and invasion are highly related with tumor metastatic potential and recurrence prediction in the most aggressive brain cancer, glioblastoma multiforme (GBM). For the first time, this study reveals that marine-sponge-derived stellettin B reduces angiogenesis and invasion. We discovered that stellettin B reduces migration of glioblastoma cells by scratch wound healing assay and invasion via chamber transwell assay. Further, stellettin B downregulates Akt/Mammalian Target of Rapamycin (Akt/mTOR) and Signal transducer and activator of transcription 3 (Stat3) signaling pathways, which are essential for invasion and angiogenesis in glioblastoma. This study further demonstrates that stellettin B affects filamentous actin (F-actin) rearrangement by decreasing the cross-linkage of phosphor-Girdin (p-Girdin), which attenuates glioblastoma cell invasion. Moreover, stellettin B blocks the expression and secretion of a major proangiogenic factor, vascular endothelial growth factor (VEGF), in glioblastoma cells. Stellettin B also reduces angiogenic tubule formation in human umbilical vein endothelial cells (HUVECs). In vivo, we observed that stellettin B decreased blood vesicle formation in developmental zebrafish and suppressed angiogenesis in Matrigel plug transplant assay in mice. Decreased VEGF transcriptional expression was also found in stellettin B&ndash, treated zebrafish embryos. Overall, we conclude that stellettin B might be a potential antiangiogenic and anti-invasion agent for future development of therapeutic agents for cancer therapy.

A natural caulerpenyne-derived sesquiterpene, oxytoxin-2 (1), was isolated from a cultured mollusc Volvatella vigourouxi. The structure of 1 was elucidated on the basis of spectroscopic analysis and this compound was suggested to be a diet-derived metabolite from the green alga Caulerpa sertularioides.-This is the first study on the chemical constituents of V. vigourouxi. Oxytoxin-2 (1) was found to inhibit significantly the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein of lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells.