Inhibition of PTEN Activity Aggravates Post Renal Fibrosis in Mice with Ischemia Reperfusion-Induced Acute Kidney Injury.

BACKGROUND: Renal fibrosis is a common pathophysiological feature of chronic kidney disease. Acute kidney injury (AKI) is defined as an independent causal factor of chronic kidney disease, with a pathological representation of post renal fibrosis. However, the etiopathogenesis underlying post renal fibrosis induced by AKI is not completely understood. METHODS: BALB/c mice were treated with bpv or vehicle controls and were, respectively, the ischemia reperfusion (IR) model group and control group. All of the animals had blood taken from the orbital venous plexus at 24 hours after IR. Six mice in each group were randomly chosen and euthanized 7 days after IR treatment, and the remaining six mice in each group were euthanized 14 days after IR treatment. We examined the effect on post kidney fibrosis of inhibiting PTEN activity in mice in an IR induced AKI experimental model. RESULTS: Compared with vehicle mice, bpv-(PTEN specific inhibitor) treated mice accumulated more bone marrow-derived fibroblasts and myofibroblasts in the kidneys. Inhibition of PTEN activity increased the expression of α-smooth muscle actin and extracellular matrix proteins and post kidney fibrosis. Furthermore, inhibition of PTEN activity resulted in more inflammatory cytokines in the kidneys of mice subjected to IR-induced renal fibrosis. Moreover, inhibition of PTEN activity up-regulated PI3K protein expression and Akt phosphorylation. CONCLUSIONS: Our study demonstrated that PTEN played an important role in post renal fibrosis in mice with ischemia reperfusion-induced AKI. These results indicated that the PTEN/PI3K/Akt signaling pathway may serve as a novel therapeutic target for AKI-induced chronic kidney disease.

Reversal of TRESK Downregulation Alleviates Neuropathic Pain by Inhibiting Activation of Gliocytes in the Spinal Cord.

Despite the consensus that activation of TWIK-related spinal cord K+ (TRESK) might contribute to the pathogenesis of chronic pain, the specific mechanisms underlying the transfer and development of pain signals still remain obscure. In the present study, we validated that TRESK was expressed in neurons instead of glial cells. Furthermore, in the SNI model of neuropathic pain (NP), downregulation of TRESK in spinal cord neurons resulted in upregulation of connexin 36 (Cx36) and connexin 43 (Cx43), both being subtypes of gap junctions in the spinal cord, with gliocytes in the spinal cord activated ultimately. Compared with SNI rats, intrathecal injection of TRESK gene recombinant adenovirus significantly downregulated the expression levels of Cx36 and Cx43 and suppressed the activation of gliocytes in the spinal cord, with hyperalgesia significantly reduced. In conclusion, TRESK contributes to the pathogenesis of NP by upregulation of synaptic transmission and activation of gliocytes.

[Activated autophagy in spinal cord contributes to maintaining diabetic neuropathic pain in rats model].

OBJECTIVE: To observe the role of autophagy in maintaining diabetic neuropathic pain in rats model. METHODS: A total of 44 male Sprague-Dawley rats were randomly divided into diabetic neuropathic (n = 36) and normal control (n = 8) groups. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) (60 mg/kg body weight, i.p) freshly dissolved in citrate buffer (pH = 4.5). For assessing the presence of mechanical hyperalgesia in diabetic rats, mechanical paw-withdrawal threshold (MWT) in response to punctuate mechanical stimuli was measured. At Week 4 post-injection, the rats with mechanical pain threshold decreasing over 50% as compared to baseline were designated as diabetic neuropathic pain rats. They were randomly divided into three groups of neuropathic pain (DP), neuropathic pain plus rapamycin (DR) and neuropathic pain plus 3-methyladenine (3-MA) (DA). The DR group received an intraperitoneal injection of rapamycin (1 mg/kg body weight) for Day 1 to Day 14 after grouping. At the same timepoint, the DA group had an intraperitoneal injection of 3-MA (2 mg/kg body weight) and the other group phosphate buffered saline (PBS) (1 ml/kg body weight). MWT was measured at week 1, 2, 3, 4 after STZ injection and at day 1, 3, 5, 7, 9, 14 after rapamycin, 3-MA or PBS injections. Spinal cord tissues were used to examine the expression of LC3, Beclin-1 and P62 protein by Western blot at Day 14 after medication. RESULTS: The mechanical threshold of group DR decreased further from Day 3 to Day 14 after rapamycin injection compared to baseline [(4.8±0.8), (4.3±0.7), (4.1±0.6), (3.6±0.5), (3.3±0.6) vs (5.3±0.9) g, P<0.05]. The mechanical threshold of group DA began to increase from Day 5 to Day 14 after 3-MA injection [(7.0±0.8), (7.7±1.0), (9.1±0.9), (9.6±1.1) vs (5.3±0.6) g, P<0.05]. The expressions of LC3-II and Beclin-1 protein in spinal cord of rapamycin-treated rats was significantly higher than those of non-supplemented diabetics (1.32±0.12 vs 1.02±0.11; 1.03±0.08 vs 0.80±0.06, P<0.05). Otherwise the expressions of these protein in spinal cord of 3-MA-treated rats were significantly lower than those of non-supplemented diabetics (0.70±0.09 vs 1.02±0.11; 0.55±0.05 vs 0.80±0.06, P<0.05). CONCLUSION: Up-regulated autophagy in spinal cord partially contributes to the maintenance of diabetic neuropathic pain.

The interaction between oxidative stress and mast cell activation plays a role in acute lung injuries induced by intestinal ischemia-reperfusion.

BACKGROUND: Both oxidative stress and mast cells are involved in acute lung injuries (ALIs) that are induced by intestinal ischemia-reperfusion (IIR). The aim of this study was to further investigate the interaction between oxidative stress and mast cells during the process of IIR-induced ALI. MATERIALS AND METHODS: Thirty adult Sprague-Dawley rats were randomly divided into five groups: sham, IIR, IIR + compound 48/80 (CP), N-acetylcysteine (NAC) + IIR, and NAC + IIR + CP. All rats except those in the sham group were subjected to 75 min of superior mesenteric artery occlusion, followed by 2 h of reperfusion. The rats in the NAC + IIR and NAC + IIR + CP groups were injected intraperitoneally with NAC (0.5 g/kg) for three successive days before undergoing IIR. The rats in the IIR + CP and NAC + IIR + CP groups were treated with CP (0.75 mg/kg), which was administered intravenously 5 min before the reperfusion. At the end of the experiment, lung tissue was obtained for pathologic and biochemical assays. RESULTS: IIR resulted in ALI, which was detected by elevated pathology scores, a higher lung wet-to-dry ratio, and decreased expression of prosurfactant protein C (P < 0.05). Concomitant elevations were observed in the expression levels of the nicotinamide adenine dinucleotide phosphate oxidase subunits p47(phox) and gp91(phox) and the levels of hydrogen peroxide and malondialdehyde. However, superoxide dismutase activity in the lung was reduced (P < 0.05). The level of interleukin 6, the activity of myeloperoxidase, and the expression of intercellular adhesion molecule 1 were also increased in the lung. IIR led to pulmonary mast cell degranulation and increases in the plasma and pulmonary ß-hexosaminidase levels, mast cell counts, and tryptase expression in lung tissue. CP aggravated these conditions, altering the measurements further, whereas NAC attenuated the IIR-induced ALI and all biochemical changes (P < 0.05). However, CP abolished some of the protective effects of NAC. CONCLUSIONS: Oxidative stress and mast cells interact with each other and promote IIR-induced ALI.

Recent Advances in Light-Conversion Phosphors for Plant Growth and Strategies for the Modulation of Photoluminescence Properties.

The advent of greenhouses greatly promoted the development of modern agriculture, which freed plants from regional and seasonal constraints. In plant growth, light plays a key role in plant photosynthesis. The photosynthesis of plants can selectively absorb light, and different light wavelengths result in different plant growth reactions. Currently, light-conversion films and plant-growth LEDs have become two effective ways to improve the efficiency of plant photosynthesis, among which phosphors are the most critical materials. This review begins with a brief introduction of the effects of light on plant growth and the various techniques for promoting plant growth. Next, we review the up-to-date development of phosphors for plant growth and discussed the luminescence centers commonly used in blue, red and far-red phosphors, as well as their photophysical properties. Then, we summarize the advantages of red and blue composite phosphors and their designing strategies. Finally, we describe several strategies for regulating the spectral position of phosphors, broadening the emission spectrum, and improving quantum efficiency and thermal stability. This review may offer a good reference for researchers improving phosphors to become more suitable for plant growth.

Sevoflurane inhibits invasion and migration of lung cancer cells by inactivating the p38 MAPK signaling pathway.

PURPOSE: Sevoflurane is used widely during lung cancer surgery. However, the effect of sevoflurane on the invasion and migration of lung carcinoma cells remains unclear. The aims of this study were to explore the role of matrix metalloproteinase (MMP)-2 and MMP-9 in the effect of sevofluane on the invasion and the role of fascin and ezrin on the effect of sevofluane on the migration of human lung adenocarcinoma A549 cells. We also investigated whether sevoflurane regulates the expression of these molecules through the p38 mitogen-activated protein kinase (MAPK) signaling pathway. METHODS: The invasion of cells was evaluated using the Transwell invasion assay, and the migration of cells was determined using the wound healing assay. The expression of MMP-2, MMP-9, ezrin, fascin, and phospho-p38 MAPK in cells was determined by western blotting. RESULTS: A significant inhibition of cell invasion and migration was found in A549 cells which had been treated with sevoflurane. The data also revealed that sevoflurane could decrease the phosphorylation level of p38 MAPK, which is involved in the downregulation of MMP-2, MMP-9, fascin, and ezrin expression, accompanied by a concomitant inhibition of the invasion and migration of A549 cells. SB203580, a p38 MAPK inhibitor, augmented the downregulation of the expression of these proteins. CONCLUSION: The anti-invasion effect of sevoflurane on A549 cells was associated with a downregulation of both MMP-2 and MMP-9 expression, while the anti-migration effect was associated with a downregulation of both fascin and ezrin expression. These effects could occur partly as a result of inactivation of the p38 MAPK signaling pathway.

Enhanced Resting-State Functional Connectivity of the Nucleus Accumbens in First-Episode, Medication-Naïve Patients With Early Onset Schizophrenia.

There is abundant evidence that early onset schizophrenia (EOS) is associated with abnormalities in widespread regions, including the cortical, striatal, and limbic areas. As a main component of the ventral striatum, the nucleus accumbens (NAc) is implicated in the pathology of schizophrenia. However, functional connection patterns of NAc in patients with schizophrenia, especially EOS, are seldom explored. A total of 78 first-episode, medication-naïve patients with EOS and 90 healthy controls were recruited in the present study, and resting-state, seed-based functional connectivity (FC) analyses were performed to investigate temporal correlations between NAc and the rest of the brain in the two groups. Additionally, correlation analyses were done between regions showing group differences in NAc functional integration and clinical features of EOS. Group comparison found enhanced FC of the NAc in the EOS group relative to the HCs with increased FC in the right superior temporal gyrus and left superior parietal gyrus with the left NAc region of interest (ROI) and elevated FC in left middle occipital gyrus with the right NAc ROI. No significant associations were found between FC strength and symptom severity as well as the age of the patients. Our findings reveal abnormally enhanced FC of the NAc with regions located in the temporal, parietal, and occipital areas, which were implicated in auditory/visual processing, sensorimotor integration, and cognitive functions. The results suggest disturbed relationships between regions subserving reward, salience processing, and regions subserving sensory processing as well as cognitive functions, which may deepen our understanding of the role of NAc in the pathology of EOS.

Facial Emotion Recognition in Schizophrenia.

Deficits in facial emotion recognition are one of the most common cognitive impairments, and they have been extensively studied in various psychiatric disorders, especially in schizophrenia. However, there is still a lack of conclusive evidence about the factors associated with schizophrenia and impairment at each stage of the disease, which poses a challenge to the clinical management of patients. Based on this, we summarize facial emotion cognition among patients with schizophrenia, introduce the internationally recognized Bruce-Young face recognition model, and review the behavioral and event-related potential studies on the recognition of emotions at each stage of the face recognition process, including suggestions for the future direction of clinical research to explore the underlying mechanisms of schizophrenia.

The roles of T-type calcium channel in the development of neuropathic pain following chronic compression of rat dorsal root ganglia.

This study aimed to elucidate the role of T-type calcium channels in the nociceptive signal transmission at the spinal level. The chronic compression of dorsal root ganglion (CCD) rat model was adopted. Three doses (50, 100 and 200 microg in groups Mib50, Mib100 and Mib200, respectively) of specific T-type Ca2+ channel inhibitors mibefradil (Mib) or normal saline (NS) were intrathecally administered on the 5th day after the CCD model had been established. The paw withdrawal latency from a noxious thermal stimulus and paw withdrawal mechanical threshold of von Frey filament was used to measure the thermal hyperalgesia and tactile allodynia, respectively. Lumbar spinal cords of the rats isolated on the 5th day after the operation were prepared to measure the mRNA expression of T-type (Cav3.1, Cav3.2 and Cav3.3) calcium channel with RT-PCR methods. The results demonstrated that CCD rats produced reliable thermal hyperalgesia and tactile allodynia after surgery. The intrathecal administration of Mib significantly suppressed thermal hyperalgesia and allodynia in CCD rats (p< 0.01), and the inhibitory effect lasted for 2 h. However, only Cav3.2 and Cav3.3 T-type calcium channel mRNA were detected in the lumbar spinal cord of rats, and there were no Cav3.1 calcium channels. Compared with native and sham groups, the Cav3.2 and Cav3.3 calcium channel mRNA expression increased significantly (p < 0.05). These data support the view that spinal T-type calcium (Cav3.2 and Cav3.3 but not Cav3.1) channels may play an important role in the pathogenesis of neuropathic pain.

Dynamic Alterations of Amplitude of Low-Frequency Fluctuations in Patients With Drug-Naïve First-Episode Early Onset Schizophrenia.

Abnormalities in static neural activity have been widely reported in early onset schizophrenia (EOS). However, dynamic brain activity alterations over time in EOS are unclear. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by EOS. A total of 78 drug-naïve first-episode patients with EOS and 90 healthy controls (HCs) were enrolled in this study. Dynamic amplitude of low-frequency fluctuations (dALFF) was performed to examine the abnormal time-varying local neural activity in EOS. Furthermore, we investigated the relationships between abnormalities in dALFF variability and clinical characteristics in EOS patients. Compared to HCs, EOS patients showed significantly decreased dALFF variability in the bilateral precuneus, right superior marginal gyrus, right post-central gyrus and increased dALFF in the right middle temporal gyrus (MTG). Moreover, increased dALFF variability in MTG was negatively associated with negative symptoms in EOS. Our findings reveal increased dynamic local neural activity in higher order networks of the cortex, suggesting that enhanced spontaneous brain activity may be a predominant neural marker for brain maturation. In addition, decreased dALFF variability in the default mode network (DMN) and limbic system may reflect unusually dynamic neural activity. This dysfunctional brain activity could distinguish between patients and HCs and deepen our understanding of the pathophysiological mechanisms of EOS.

Cobalt-Doped NiS2 Micro/Nanostructures with Complete Solid Solubility as High-Performance Cathode Materials for Actual High-Specific-Energy Thermal Batteries.

Transition-metal sulfides are key cathode materials for thermal batteries used in military applications. However, it is still a big challenge to prepare sulfides with good electronic conductivity and thermal stability. Herein, we rapidly synthesized a Co-doped NiS2 micro/nanostructure using a hydrothermal method. We found that the specific capacity of the Ni1-xCoxS2 micro/nanostructure increases with the amount of Co doping. Under a current density of 100 mA cm-2, the specific capacity of Ni0.5Co0.5S2 was about 1565.2 As g-1 (434.8 mAh g-1) with a cutoff voltage of 1.5 V. Owing to the small polarization impedance (5 mΩ), the pulse voltage reaches about 1.74 V under a pulse current of 2.5 A cm-2, 30 ms. Additionally, the discharge mechanism was proposed by analyzing the discharge product according to the anionic redox chemistry. Furthermore, a 3.9 kg full thermal battery is assembled based on the synthesized Ni0.5Co0.5S2 cathode materials. Notably, the full thermal battery discharges at a current density of 100 mA cm-2, with an operating time of about 4000 s, enabling a high specific energy density of around 142.5 Wh kg-1. In summary, this work presents an effective cathode material for thermal battery with high specific energy and long operating life.

The Principles of Electroconvulsive Therapy Based on Correlations of Schizophrenia and Epilepsy: A View From Brain Networks.

Electroconvulsive therapy (ECT) was established based on Meduna's hypothesis that there is an antagonism between schizophrenia and epilepsy, and that the induction of a seizure could alleviate the symptoms of schizophrenia. However, subsequent investigations of the mechanisms of ECT have largely ignored this originally established relationship between these two disorders. With the development of functional magnetic resonance imaging (fMRI), brain-network studies have demonstrated that schizophrenia and epilepsy share common dysfunctions in the default-mode network (DMN), saliency network (SN), dorsal-attention network (DAN), and central-executive network (CEN). Additionally, fMRI-defined brain networks have also been shown to be useful in the evaluation of the treatment efficacy of ECT. Here, we compared the ECT-induced changes in the pathological conditions between schizophrenia and epilepsy in order to offer further insight as to whether the mechanisms of ECT are truly based on antagonistic and/or affinitive relationships between these two disorders.

Cardioprotection of sevoflurane postconditioning by activating extracellular signal-regulated kinase 1/2 in isolated rat hearts.

AIM: The activation of extracellular signal-regulated kinase (ERK)1/2 protects against ischemic-reperfusion injury. Whether ERK1/2 mediates the cardioprotection of sevoflurane postconditioning is unknown. We tested whether sevoflurane postconditioning produces cardioprotection via an ERK1/2-dependent mechanism. METHODS: In protocol 1, Langendorff-perfused Sprague-Dawley rat hearts (n=84, 12 per group), with the exception of the Sham group, were subjected to 30 min ischemia followed by 90 min reperfusion and were assigned to the untreated (control) group, followed by 4 cycles of ischemic postconditioning (25 s of each), 3% (v/v) sevoflurane postconditioning (for 5 min and 10 min of washout), and the PD98059 solvent DMSO (<0.2%), ERK1/2 inhibitor PD98059 (20 micromol/L), and Sevo+PD administration. Left ventricular hemodynamics and coronary flow at 30 min of equilibrium were recorded at 30, 60, and 90 min of reperfusion, respectively. Acute infarct size was measured by triphenyltetrazolium chloride staining. The configuration of mitochondria was observed by an electron microscope. Western blot analysis was used to determine the contents of cytosolic and mitochondrial cytochrome c at the end of reperfusion. In protocol 2, after 15 min of reperfusion, the expression of total and phosphorylated forms of ERK1/2 and its downstream target p70S6K was determined by Western blotting. RESULTS: No differences in baseline hemodynamics were observed among the experimental groups (P>0.05). After reperfusion, compared with the control group, sevoflurane postconditioning and ischemic postconditioning significantly(P<0.05) improved functional recovery and largely (P<0.05) decreased myocardial infarct size (22.9%+/-4.6% and 21.2%+/-3.8%, vs 39.4%+/- 5.7%, both P<0.05). Sevoflurane-mediated protection was abolished by PD98059. CONCLUSION: Anesthetic postconditioning by sevoflurane effectively protects against reperfusion damage by activating ERK1/2 in vitro.

Sevoflurane post-conditioning protects against myocardial reperfusion injury by activation of phosphatidylinositol-3-kinase signal transduction.

The mechanisms underlying myocardial protection by sevoflurane post-conditioning are unclear. In the present study, we tested two hypotheses: (i) that sevoflurane post-conditioning produces cardioprotection via a phosphatidylinositol-3-kinase (PI3-K)-dependent pathway; and (ii) combining sevoflurane and ischaemic post-conditioning offers an additional benefit against reperfusion injury. Rat isolated perfused hearts were exposed to 25 min ischaemia followed by 90 min reperfusion. Sevoflurane post-conditioning was induced by administration of sevoflurane (3.0 vol%) for 15 min from the onset of reperfusion. In some groups, 15 micromol/L LY294002, a selective PI3-K inhibitor, was coadministrated with sevoflurane. Other groups of hearts were exposed to ischaemic post-conditioning or combined sevoflurane plus ischaemic post-conditioning in the presence and absence of LY294002. After 15 min reperfusion, phosphorylation of Akt and glycogen synthase kinase 3beta (GSK3beta) was determined by Western blot analysis. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining and subsarcolemmal mitochondrial lesions were assessed by electron microscopy after 90 min reperfusion. Sevoflurane post-conditioning significantly decreased infarct size compared with control hearts (31 +/- 2 vs 42 +/- 3%, respectively; P < 0.05), diminished mitochondrial lesions and increased phosphorylation of Akt and GSK3beta, as did ischaemic post-conditioning. However, combined sevoflurane plus ischaemic post-conditioning did not further improve the cardioprotective effects compared with either intervention alone. Sevoflurane-mediated cardioprotection was abolished or inhibited by 15 micromol/L LY294002. In conclusion, sevoflurane acts during early reperfusion after ischaemia to salvage the myocardium by activating PI3-K. The combination of sevoflurane plus ischaemic post-conditioning does not offer any additional benefit over either intervention alone.

Electrically Enhanced Self-Thermophoresis of Laser-Heated Janus Particles under a Rotating Electric Field.

The motion of a laser-heated Janus particle is experimentally measured under a rotating electric field. Directionally circular motions of the Janus particle following or countering the direction of the rotating electric field are observed in the low-frequency region (from 1 to 6 kHz) depending on the direction of electrorotation. In the higher frequency region (>10 kHz), only pure electrorotation and electrothermal flow are observed. By measuring the dependence of the frequency, voltage, and laser heating power, we propose that the tangential component of circular motion is caused by electric field enhanced self-thermophoresis, which is proportional to the laser heating power and the electric field. This result indicates that thermophoresis could be modified by the induced zeta potential of the Janus particle tuned by the applied electric fields. By this mechanism, the intrinsic thermophoresis can be enhanced several times at a relatively low applied voltage (~3 Volt). Electrically tunable thermophoresis of a particle may bring new insights to thermophoresis phenomenon and also open a new direction for tunable active materials.

TAK1 as the mediator in the protective effect of propofol on renal interstitial fibrosis induced by ischemia/reperfusion injury.

Ischemia-reperfusion injury (IRI), which is a major cause of acute and chronic renal dysfunction, induces both apoptosis and fibrotic processes. The mitogen-activated protein kinase kinase kinase transforming growth factor-ß-activated kinase 1 (TAK1) was implicated in the processes of inflammation and fibrosis. The protective effect of propofol on renal functionality after acute kidney injury (AKI) in mice has been identified, whereas the mechanisms underlying fibrosis induced by kidney injury remain obscure. Herein, we investigated whether the protective effect of propofol on renal interstitial fibrosis induced by ischemia/reperfusion injury was modulated by TAK1 in renal ischemia /reperfusion (I/R) mouse models. The results of immunohistochemistry and western blotting revealed that TAK1 was significantly upregulated in IR group versus the control group, which was reversed by propofol administration. In addition, fibronectin (FN), α-smooth muscle actin (α-SMA) and type I collagen (COL1) were significantly downregulated and Tunnel staining revealed the number of tubular apoptotic cells was markedly reduced in IRP group versus IR group. Collectively, our results validated that propofol could ameliorate the IRI-induced renal interstitial fibrosis in mice by downregulation of TAK1 and inhibition of apoptosis at the early stage.

The effects of propofol on the growth behavior of hepatoma xenografts in Balb/c mice.

OBJECTIVE: Studies on the effects of propofol on the growth of hepatoma xenografts in Balb/c mice. METHODS: In an effort to establish a hepatoma-xenograft model of BALB/C mice, human hepatocellular carcinoma cells SMMC-7721 were inoculated subcutaneously into BALB/C mice. Forty mice were randomly divided into five different groups (n=8): control group (C group), Intralipid group (Y group), low dose (50mg/kg) propofol group (P1 group), medium dose (100mg/kg) propofol group (P2 group) and high dose (150mg/kg) propofol group (P3 group). The tumor volume was measured before treatment and every 3days after treatment (T0d-T18d, T0 represents time point before treatment, T3d-T18d represent time points every 3days after treatment for a total of 18 days). All mice were sacrificed 19days after drug withdrawal. The tumor masses were extracted, weighed, and the tumor inhibition rate of propofol was calculated. The protein levels of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in the xenografted tumors were analyzed by immunohistochemistry staining. RESULTS: No statistical significance in the tumor volume at T0d (before treatment), T3d (3days after treatment), and T6d (6days after treatment) among the five groups (P>0.05) could be determined. Compared to group C, the tumor volumes in the P1, P2, and P3 groups were found to be significantly decreased in size upon increasing the propofol dosages (P<0.05). There was no statistical significance at time points T9d-T18d in group Y compared to group C (P>0.05). The tumor weights in the P1, P2, and P3 groups were found to be significantly lower as the propofol dosages increased (P<0.05), with no statistical significance determined in group Y (P>0.05). MMP-2 and VEGF protein levels were found to be significantly lower in the P1, P2, and P3 groups as the propofol dosages increased (P<0.05), with no statistical significance in group Y (P>0.05). CONCLUSION: Within a certain range, propofol was found to inhibit tumor growth and expression of MMP-2 and VEGF proteins in hepatoma xenografts in BALB/C mice in a dose-dependent manner.

Identification of the Spinal Expression Profile of Non-coding RNAs Involved in Neuropathic Pain Following Spared Nerve Injury by Sequence Analysis.

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in aberrant pain, which is associated with gene expression changes in the sensory pathway. However, the molecular mechanisms are not fully understood. A non-coding Ribose Nucleic Acid (ncRNA) is an RNA molecule that is not translated into a protein. NcRNAs are involved in many cellular processes, and mutations or imbalances of the repertoire within the body can cause a variety of diseases. Although ncRNAs have recently been shown to play a role in NP pathogenesis, the specific effects of ncRNAs in NP remain largely unknown. In this study, sequencing analysis was performed to investigated the expression patterns of ncRNAs in the spinal cord following spared nerve injury-induced NP. A total of 134 long non-coding RNAs (lncRNAs), 12 microRNAs (miRNAs), 188 circular RNAs (circRNAs) and 1066 mRNAs were significantly regulated at 14 days after spared nerve injury (SNI) surgery. Next, quantitative real-time polymerase chain reaction (PCR) was performed to validate the expression of selected lncRNAs, miRNAs, circRNAs, and mRNAs. Bioinformatics tools and databases were employed to explore the potential ncRNA functions and relationships. Our data showed that the most significantly involved pathways in SNI pathogenesis were ribosome, PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, amoebiasis and protein digestion and absorption. In addition, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA network of NP was constructed. This is the first study to comprehensively identify regulated ncRNAs of the spinal cord and to demonstrate the involvement of different ncRNA expression patterns in the spinal cord of NP pathogenesis by sequence analysis. This information will enable further research on the pathogenesis of NP and facilitate the development of novel NP therapeutics targeting ncRNAs.

Inhibition of PTEN activity aggravates cisplatin-induced acute kidney injury.

Cisplatin (cis-Diamminedichloroplatinum II) has been widely and effectively used in chemotherapy against tumors. Nephrotoxicity due to cisplatin is one of the most common clinical causes of acute kidney injury (AKI), which has a poor prognosis and high mortality. The signaling mechanisms underlying cisplatin-induced AKI are not completely understood. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that negatively regulates the cell-survival pathway and is considered a double-edged sword in organ damage. In this study, we examined the effect that inhibiting PTEN activity in experimental models of cisplatin-induced AKI had on the degrees of AKI. Compared with vehicle mice, mice treated with bpV(pic) (specific inhibitor of PTEN) had exacerbated renal damage due to cisplatin-induced AKI. Furthermore, inhibition of PTEN activity increased cell apoptosis in the kidneys of mice induced by cisplatin. More inflammatory cytokines were activated after cisplatin treatment in mice of the bpV(pic)-treated group compared with vehicle mice, and these inflammatory cytokines may be partially derived from bone marrow cells. In addition, inhibiting PTEN activity decreased the phosphorylation of p53 in the pathogenesis of cisplatin-induced AKI. In summary, our study has demonstrated that inhibiting PTEN activity aggravates cisplatin-induced AKI via apoptosis, inflammatory reaction, and p53 signaling pathway. These results indicated that PTEN may serve as a novel therapeutic target for cisplatin-induced AKI.

Effect of the spinal apelin­APJ system on the pathogenesis of chronic constriction injury­induced neuropathic pain in rats.

Apelin is hypothesized to serve a dual function in pain processing. Spinal administration of apelin induces hyperalgesia, while opioid receptors are implicated in the antinociceptive effects of apelin in acute nociceptive models. However, whether the apelin­apelin receptor (APJ) system is involved in neuropathic pain remains to be elucidated. The present study aimed to evaluate the impact and mechanism of the spinal apelin­APJ system in neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve produced sustained spinal apelin and APJ upregulation, which was associated with mechanical allodynia and heat hyperalgesia development in the hind­paw plantar surface. Immunofluorescence demonstrated that apelin and APJ were localized to the superficial dorsal horns. In order to further clarify the function of the apelin­APJ system, a single intrathecal administration of ML221, an APJ antagonist, was used; this transiently reduced CCI­induced pain hypersensitivity. However, apelin­13 (the isoform which binds most strongly to APJ) exhibited no effect on the nociceptive response, suggesting an essential role for the spinal apelin­APJ system in neuropathic pain sensitization. The present study demonstrated that a single application of ML221 alleviated mechanical allodynia and heat hyperalgesia 7 days following CCI, in a dose­dependent manner. Intraspinal delivery of ML221, at the onset of and in fully­established neuropathic pain, persistently attenuated CCI­induced pain hypersensitivity, indicating that the apelin­APJ system was involved in initiating and maintaining pain. It was demonstrated, using immunoblotting, that intrathecal ML221 downregulated phosphorylated extracellular signal­related kinase (ERK) in the rat spinal cord dorsal horn, suggesting that the effect of apelin on neuropathic pain may be mediated via ERK signaling. The results of the present study suggested that the spinal apelin­APJ system may drive neuropathic pain. Inhibition of APJ may provide novel pharmacological interventions for neuropathic pain.