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.

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.

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.

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.

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.

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.

Interleukin-33 signaling contributes to renal fibrosis following ischemia reperfusion.

Acute kidney injury caused by ischemia-reperfusion injury (IRI) is a major risk factor for chronic kidney disease, which is characterized by renal interstitial fibrosis. However, the molecular mechanisms underlying renal fibrosis induced by IRI are not fully understood. Our results showed that interleukin (IL)-33 was induced markedly after IRI insult, and the kidneys of mice following IRI plus IL-33 treatment presented more severe renal fibrosis compared with mice treated with IRI alone. Therefore, we investigated whether inhibition of IL-33 protects against IRI-induced renal fibrosis. Mice were administrated with soluble ST2 (sST2), a decoy receptor that neutralizes IL-33 activity, or vehicle by intraperitoneal injection for 14 days after IRI challenge. We revealed that mice treated with sST2 exhibited less severe renal dysfunction and fibrosis in response to IRI compared with vehicle-treated mice. Inhibition of IL-33 suppressed bone marrow-derived fibroblast accumulation and myofibroblast formation in the kidneys after IRI stress, which was associated with less expression of extracellular matrix proteins. Furthermore, inhibition of IL-33 also showed a significant reduction of F4/80+ macrophages and CD3+ T cells in the kidneys of mice after IRI treatment. Finally, Treatment with IL-33 inhibitor reduced proinflammatory cytokine and chemokine levels in the kidneys of mice following IRI insult. Taken together, our findings indicate that IL-33 signaling plays a critical role in the pathogenesis of IRI-induced renal fibrosis through regulating myeloid fibroblast accumulation, inflammation cell infiltration, and the expression of proinflammatory cytokines and chemokines.

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.

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.

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.

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.

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.

TRESK contributes to pain threshold changes by mediating apoptosis via MAPK pathway in the spinal cord.

The mechanism underlying neuropathic pain (NP) is complex and has not been fully elucidated. The TWIK-related spinal cord K+ (TRESK) is the major background potassium current in dorsal root ganglia (DRG), we found that mitogen-activated protein kinase (MAPK) signal pathway were activated in spinal cord accompanied by TRESK down regulation in response to NP. Therefore, we investigated whether TRESK mediates inflammation and apoptosis by MAPK pathway in the spinal cord of NP rats. SNI rats exhibited reduced TRESK expression in DRG and spinal cord and higher sensitivity to mechanical stimuli but no effect on thermal stimuli. Intrathecal injections of TRESK overexpressing adenovirus alleviated mechanical allodynia, inhibited phosphorylation of extracellular signal-regulated kinase (ERK) and p38, and decreased inflammatory reactions and apoptosis in the spinal cords of SNI rats. Down regulation of TRESK in DRG and spinal cord was detected in normal rats after intrathecal TRESK shRNA lentivirus injection, which induced mechanical allodynia but had no effect on pain thresholds for heat stimulation. Phosphorylated ERK and p38 were increased in the spinal cord. Intrathecal injection of an ERK antagonist (PD98059) and p38 antagonist (SB203580) prevented ERK and p38 activation in the spinal cord and mechanical allodynia induced by TRESK shRNA lentivirus. In conclusion, our study clearly demonstrated an important role for TRESK in NP and that TRESK regulation contributes to pain sensitivity mediates inflammation and apoptosis by ERK and p38 MAPK signaling in the spinal cord.

Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1µg, 3µg, or 10µg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN.

[Role of calmodulin-dependent protein kinase II in bupivacaine hydrochloride-induced injury of SH-SY5Y cells].

OBJECTIVE: To investigate the effect of KN93, a calmodulin-dependent protein kinase II (CaMK II) inhibitor, on SH-SY5Y cell injury induced by bupivacaine hydrochloride. METHODS: SH-SY5Y cells exposed for 24 h to 1 mmol/L KN93, 1 mmol/L bupivacaine hydrochloride, or both were examined for morphological changes and Cav3.1 protein expressions using Western blotting. The vitality and apoptosis rate of the cells at different time points during the exposures were assessed with MTT assay and flow cytometry, respectively. RESULTS: Bupivacaine hydrochloride exposure caused obvious cell morphologial changes, reduced cell viability, increased cell apoptosis, and enhanced Cav3.1 protein expression. All these changes were partly reversed by treatment of the cells with 1 mmol/L KN93. CONCLUSIONS: CaMKII may play a role in bupivacaine hydrochloride-induced SH-SY5Y cells injury, which is related with upregulated Cav3.1 protein expression.

[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.

Hydroxyethyl starch 200/0.5 decreases circulating tumor cells of colorectal cancer patients and reduces metastatic potential of colon cancer cell line through inhibiting platelets activation.

Platelets play an important role in metastasis of circulating tumor cells (CTCs). It has been demonstrated that hydroxyethyl starch (HES) inhibits platelets function. However, the effect of HES on CTCs in patients with colorectal cancer remains unclear. We compared the effects of HES 200/0.5 and HES 130/0.4 on CTCs and platelets activation of colorectal patients in this study. Additionally, the effects of HES 200/0.5 or HES 130/0.4 on metastasis ability of colon cancer cell line that stimulated by activated platelets have been explored. In vivo, 90 patients undergoing colorectal cancer radical surgery received randomly 15 mL/kg of HES 200/0.5 (n = 45) or HES 130/0.4 (n = 45) infusion before surgery. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa), CD62P and platelets aggregation rate (PAR) were evaluated pre-, intra- and postoperatively. Cytokeratin-20 (CK-20) mRNA was detected by reverse transcriptase polymerase chain reaction before and after surgery. In vitro, colon cancer SW480 cells were incubated with activated platelets in the presence or absence HES 200/0.5 or HES 130/0.4. The metastasis ability of SW480 cells was assessed by Transwell assay. The results showed that CK-20 mRNA positive rate in HES 200/0.5 group after surgery was decreased significantly as compared to group HES 130/0.4 (χ (2) = 6.164, P = 0.013). Simultaneously, a more pronounced inhibition of platelets activation was observed in group HES 200/0.5. A positive correlation between platelets activation marker and CK-20 mRNA positive rate was found. In vitro, HES 200/0.5, but not HES 130/0.4, decreased the invasion and migration ability of SW480 cells that induced by activated platelets. Besides, the expression of GPIIb/IIIa, CD62P and PAR was inhibited more strongly in group HES 200/0.5 than those in group HES 130/0.4. In summary, we found that HES 200/0.5 significantly decreased CTCs of patients undergoing colorectal cancer radical surgery as compared to HES 130/0.4, which might be associated with inhibiting platelets activation of HES 200/0.5. Furthermore, HES 200/0.5, but not HES 130/0.4, reduced the metastatic potential of colon cell line stimulated by activated platelets through depressing platelets activation. Modulation of platelets activity may be a novel strategy to minimize the risk of metastasis during surgery.