Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Exaggerated activities of TRPM7 underlie bupivacaine-induced neurotoxicity in the SH-SY5Y cells preconditioned with high glucose.

Hyperglycemia is considered a risk factor for the enhancement of local anesthetic-induced neurotoxicity. Transient receptor potential melastatin 7 (TRPM7), a kinase-coupled cation channel, has been implicated in a variety of neuropathological processes, including intracellular calcium disturbance and high glucose-induced neuropathy. In this study, we investigated whether TRPM7-related pathophysiology is involved in bupivacaine-induced neurotoxicity in SH-SY5Y cells and how hyperglycemia acts as a risk factor. For initial neurotoxicity evaluation, it was confirmed that cell damage and apoptosis induced by acute exposure to bupivacaine were dependent on its concentration and glucose preconditioning. High glucose preconditioning facilitated the bupivacaine-induced fast and temporary rise in intracellular free calcium concentration ([Ca2+ ]i ), which was attributed to both calcium influx through TRPM7 and calcium store release. Additionally, bupivacaine was shown to increase TRPM7-like currents, particularly in cells preconditioned with high glucose. Bupivacaine-induced neurotoxicity in hyperglycemia was correlated with extracellular signal-regulated kinase (ERK), but not protein kinase B (AKT) activation. Inhibition of TRPM7 and ERK activity alleviates bupivacaine neurotoxicity. These results suggest that therapeutically targeting TRPM7-related pathophysiological changes could be a potential strategy for treating local anesthetic-induced neurotoxicity exacerbated by hyperglycemia.

Response of Chinese Anesthesiologists to the COVID-19 Outbreak.

The coronavirus disease 2019, named COVID-19 officially by the World Health Organization (Geneva, Switzerland) on February 12, 2020, has spread at unprecedented speed. After the first outbreak in Wuhan, China, Chinese anesthesiologists encountered increasing numbers of infected patients since December 2019. Because the main route of transmission is via respiratory droplets and close contact, anesthesia providers are at a high risk when responding to the devastating mass emergency. So far, actions have been taken including but not limited to nationwide actions and online education regarding special procedures of airway management, oxygen therapy, ventilation support, hemodynamic management, sedation, and analgesia. As the epidemic situation has lasted for months (thus far), special platforms have also been set up to provide free mental health care to all anesthesia providers participating in acute and critical caring for COVID-19 patients. The current article documents the actions taken, lesson learned, and future work needed.

Inhibition of NLRP3 Inflammasome Ameliorates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice.

Sustained activation of NLRP3 inflammasome is closely related to diabetes and stroke. However, it is unknown whether NLRP3 inflammasome plays an essential role in stroke in diabetes. We aim to investigate the effect and the potential mechanism of NLRP3 inflammasome in diabetic mice with cerebral ischemia-reperfusion injury. A type 2 diabetic mouse model was induced by a high-fat diet and streptozotocin (STZ). Diabetic mice received MCC950 (the specific molecule NLRP3 inhibitor) or vehicle 60 minutes before the middle cerebral artery occlusion (MCAO) and reperfusion. MCC950 reduced the neurological deficit score of 24 h after cerebral ischemia reperfusion and improved the 28-day survival rate of cerebral ischemia-reperfusion injury in diabetic mice. Furthermore, we found that the mRNA transcription levels of NLRP3, IL-1ß, and caspase-1 in the core ischemic area were remarkably amplified in diabetic mice with cerebral ischemia-reperfusion injury, whereas this phenomenon was obviously attenuated by MCC950 pretreatment. In conclusion, the NLRP3 inflammasome was involved in the complex diseases of diabetic stroke. MCC950, the NLRP3 specific inhibitor, ameliorated diabetic mice with cerebral ischemia-reperfusion injury and improved the 28-day survival rate during the recovery stage of ischemic stroke.

Waste anesthetic gas exposure and strategies for solution.

As inhaled anesthetics are widely used, medical staff have inevitably suffered from exposure to anesthetic waste gases (WAGs). Whether chronic exposure to WAGs has an impact on the health of medical staff has long been a common concern, but conclusions are not consistent. Many measures and equipment have been proposed to reduce the concentration of WAGs as far as possible. This review aims to dissect the current exposure to WAGs and its influence on medical staff in the workplace and the environment, and summarize strategies to reduce WAGs.

Diphenyleneiodonium Mitigates Bupivacaine-Induced Sciatic Nerve Damage in a Diabetic Neuropathy Rat Model by Attenuating Oxidative Stress.

BACKGROUND: Increased oxidative stress has been linked to local anesthetic-induced nerve injury in a diabetic neuropathy (DN) rat model. The current study explores the effects of diphenyleneiodonium (DPI) chloride, an NADPH oxidase (NOX) inhibitor, on bupivacaine-induced sciatic nerve injury in DN rats. METHODS: A rat DN model was established through high-fat diet feeding and streptozotocin injection. The model was confirmed via testing (i) blood glucose, (ii) hindpaw allodynia responses to von Frey (VF) monofilaments, (iii) paw withdrawal thermal latency (PWTL), and (iv) nerve conduction velocity (NCV). Bupivacaine (Bup, 0.2 mL, 5 mg/mL) was used to block the right sciatic nerve. DPI (1 mg/kg) was injected subcutaneously 24 hours and 30 minutes before the sciatic block. At 24 hours after the block, NCV, various reactive oxygen species, and Caspase-3 were evaluated to determine the extent of sciatic nerve injury. RESULTS: The DN rat model was successfully established. Compared with the DN control group, the postblock values of VF responses (DN-Con, 16.5 ± 1.3 g; DN + Bup, 19.1 ± 1.5 g, P < .001) and PWTL significantly increased (DN-Con, 13.3 ± 1.1 seconds; DN + Bup, 14.6 ± 1.1 seconds, P = .028); the NCV of sciatic nerve was significantly reduced (DN-Con, 38.8 ± 2.4 m/s, DN + Bup, 30.5 ± 2.0 m/s, P = .003), and sciatic nerve injury (as indicated by axonal area) was more severe in the bupivacaine-treated DN group (DN-Con, 11.6 ± 0.3 µm, DN + Bup, 7.5 ± 0.3 µm, P < .001). In addition, DPI treatment significantly improved nerve function (VF responses, 17.3 ± 1.3 g; PWTL, 13.4 ± 1.1 seconds; NCV, 35.6 ± 3.1 m/s) and mitigated loss of axonal area (9.6 ± 0.3 µm). Compared to the DN + Bup group (without DPI), the levels of lipid peroxides and hydroperoxides, as well as the protein expression of NOX2, NOX4, and Caspase-3, were significantly reduced in the DN + Bup + DPI group (P < .05). CONCLUSIONS: Subcutaneous injection of DPI appears to protect against the functional and neurohistological damage of bupivacaine-blocked sciatic nerves in a high-fat diet/streptozotocin-induced DN model.

Adipose-derived mesenchymal stem cells therapy for acute kidney injury induced by ischemia-reperfusion in a rat model.

Acute kidney injury (AKI) represents a group of complicated syndromes with a high mortality rate. The administration of adipose-derived mesenchymal stem cells (ADMSCs) has been tested as a possible treatment method for AKI. The long-term evaluation of AKI induced by ischemia/reperfusion (IR) and the probable renal protection of ADMSCs are limited. In this study we have established a rat AKI model induced by IR and investigated the possible protective effects of ADMSCs. Adult Sprague-Dawley (SD) rats were divided into three groups (n = 6/each group). The MOCK group was as the normal control. Rats in the IR-AKI and IR-AKI+ADMSCs groups were subjected to IR injury by clamping both renal pedicles for 40 minutes. Rats in the MOCK and IR-AKI groups were injected with PBS via the tail vein as negative treatment controls. Rats in the IR-AKI+ADMSCs group received ADMSCs therapy (2 × 106 cells were injected into the rats via the tail vein). We found that ADMSC transplantation restored the pathologic morphology induced by IR-AKI to normal compared with the MOCK group, suggesting the reparative function of ADMSCs in kidney tissues. Compared with IR-induced AKI alone, ADMSC treatment significantly decreased the number of apoptotic cells, the level of total urinary protein and serum creatinine, the expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß, IFN-γ, TNF-α, IFN-γ, and TGF-ß), and the inflammation-associated proteins (HGF and SDF1), but increased the expression of the anti-inflammatory cytokine, IL-10, and the anti-apoptotic regulator, Bcl-2. Our data have indicated that ADMSC transplantation may protect against IR-induced AKI by anti-apoptotic and anti-inflammatory effects.

iTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways.

Bupivacaine, a commonly used local anesthetic, has potential neurotoxicity through diverse signaling pathways. However, the key mechanism of bupivacaine-induced neurotoxicity remains unclear. Cultured human SH-SY5Y neuroblastoma cells were treated (bupivacaine) or untreated (control) with bupivacaine for 24 h. Compared to the control group, bupivacaine significantly increased cyto-inhibition, cellular reactive oxygen species, DNA damage, mitochondrial injury, apoptosis (increased TUNEL-positive cells, cleaved caspase 3, and Bcl-2/Bax), and activated autophagy (enhanced LC3II/LC3I ratio). To explore changes in protein expression and intercommunication among the pathways involved in bupivacaine-induced neurotoxicity, an 8-plex iTRAQ proteomic technique and bioinformatics analysis were performed. Compared to the control group, 241 differentially expressed proteins were identified, of which, 145 were up-regulated and 96 were down-regulated. Bioinformatics analysis of the cross-talk between the significant proteins with altered expression in bupivacaine-induced neurotoxicity indicated that phosphatidyl-3-kinase (PI3K) was the most frequently targeted protein in each of the interactions. We further confirmed these results by determining the downstream targets of the identified signaling pathways (PI3K, Akt, FoxO1, Erk, and JNK). In conclusion, our study demonstrated that PI3K may play a central role in contacting and regulating the signaling pathways that contribute to bupivacaine-induced neurotoxicity.

Curcumin Attenuated Bupivacaine-Induced Neurotoxicity in SH-SY5Y Cells Via Activation of the Akt Signaling Pathway.

Bupivacaine is widely used for regional anesthesia, spinal anesthesia, and pain management. However, bupivacaine could cause neuronal injury. Curcumin, a low molecular weight polyphenol, has a variety of bioactivities and may exert neuroprotective effects against damage induced by some stimuli. In the present study, we tested whether curcumin could attenuate bupivacaine-induced neurotoxicity in SH-SY5Y cells. Cell injury was evaluated by examining cell viability, mitochondrial damage and apoptosis. We also investigated the levels of activation of the Akt signaling pathway and the effect of Akt inhibition by triciribine on cell injury following bupivacaine and curcumin treatment. Our findings showed that the bupivacaine treatment could induce neurotoxicity. Pretreatment of the SH-SY5Y cells with curcumin significantly attenuated bupivacaine-induced neurotoxicity. Interestingly, the curcumin treatment increased the levels of Akt phosphorylation. More significantly, the pharmacological inhibition of Akt abolished the cytoprotective effect of curcumin against bupivacaine-induced cell injury. Our data suggest that pretreating SH-SY5Y cells with curcumin provides a protective effect on bupivacaine-induced neuronal injury via activation of the Akt signaling pathway.

Advanced glycation end products activate the miRNA/RhoA/ROCK2 pathway in endothelial cells.

OBJECTIVE: AGEs induce endothelial cell dysfunction in HUVECs, resulting in ROS production and triggering apoptosis. This study sought to identify miRNAs involved in AGE-induced endothelial cell injury. METHODS: Microarray analysis to identify miRNAs altered with AGE stimulation was undertaken, and results were confirmed using real-time quantitative polymerase chain reaction. The interaction of miRNAs with the RhoA and ROCK2 genes was confirmed using luciferase assays, and their effects on expression were determined using Western blot analysis. The effects of AGEs and miRNAs on endothelial cell permeability were assessed. RESULTS: AGEs induced ROS production and apoptosis of HUVECs (p < 0.05). AGE-induced miR-200b and miR-200c downregulation led to increased expression of their target genes, RhoA and ROCK, respectively. AGE-induced endothelial cell permeability and F-actin expression were significantly reduced with both miR-200b and miR-200c mimics (p < 0.05). Furthermore, AGE-induced stress fiber formation was reduced in cells treated with miR-200b mimics. CONCLUSION: miR-200b and miR-200c are suppressed in AGE-induced endothelial cell injury, resulting in unregulated RhoA/ROCK2 signaling. Further studies are necessary to evaluate the therapeutic value of targeting miRNAs or their target genes for treatment of vascular diseases.

Pyriform sinus localization-assisted blind intubation: comparison with laryngoscopic intubation.

BACKGROUND: Conventional endotracheal intubation requires laryngoscopy for a direct view of the glottis. However, laryngoscopy is associated with many potential complications. The aim of the present study was to compare the efficacy and safety of pyriform sinus localization-assisted blind orotracheal intubation with those of conventional laryngoscopic orotracheal intubation. MATERIAL AND METHODS: A randomized, patient-blind, prospective study of 300 patients who underwent various operations was performed. One hundred patients were assigned to the laryngoscopic intubation group (laryngoscopy group), and 200 patients were assigned to the blind intubation group (blind group). RESULTS: The total intubation success rate in the blind group was similar to that in the laryngoscopy group (100% vs. 99%, respectively; p=0.33). Oxygen saturation by pulse oximetry in both groups was maintained at >98%. The intubation time was significantly shorter in the blind group than in the laryngoscopy group (9.7±3.4 s vs. 23.0±5.8 s, respectively; p<0.001). Postoperative complication rates were significantly lower in the blind group than in the laryngoscopy group. Recovery time from these symptoms was significantly shorter in the blind group than in the laryngoscopy group (p=0.004). CONCLUSIONS: Pyriform sinus localization-assisted blind orotracheal intubation was shown to be more effective than conventional laryngoscopic orotracheal intubation in terms of success rate, intubation time, and postoperative complication rate. Moreover, it is less affected by common risk factors; thus, this method may be more beneficial in patients with difficult airways.

Decreased connexin 40 expression of the sinoatrial node mediates ischemic stroke-induced arrhythmia in mice.

BACKGROUND: Arrhythmia is the most common cardiac complication after ischemic stroke. Connexin 40 is the staple component of gap junctions, which influences the propagation of cardiac electrical signals in the sinoatrial node. However, the role of connexin 40 in post-stroke arrhythmia remains unclear. METHODS: In this study, a permanent middle cerebral artery occlusion model was used to simulate the occurrence of an ischemic stroke. Subsequently, an electrocardiogram was utilized to record and assess variations in electrocardiogram measures. In addition, optical tissue clearing and whole-mount immunofluorescence staining were used to confirm the anatomical localization of the sinoatrial node, and the sinoatrial node tissue was collected for RNA sequencing to screen for potential pathological mechanisms. Lastly, the rAAV9-Gja5 virus was injected with ultrasound guidance into the heart to increase Cx40 expression in the sinoatrial node. RESULTS: We demonstrated that the mice suffering from a permanent middle cerebral artery occlusion displayed significant arrhythmia, including atrial fibrillation, premature ventricular contractions, atrioventricular block, and abnormal electrocardiogram parameters. Of note, we observed a decrease in connexin 40 expression within the sinoatrial node after the ischemic stroke via RNA sequencing and western blot. Furthermore, rAAV9-Gja5 treatment ameliorated the occurrence of arrhythmia following stroke. CONCLUSIONS: In conclusion, decreased connexin 40 expression in the sinoatrial node contributed to the ischemic stroke-induced cardiac arrhythmia. Therefore, enhancing connexin 40 expression holds promise as a potential therapeutic approach for ischemic stroke-induced arrhythmia.

Boron Cluster Renders Organic Radicals Water-Stable for Photothermal Anti-Infections.

Water-stable organic radicals are promising photothermal conversion candidates for photothermal therapy (PTT). However, organic radicals are usually unstable in biological environments, which greatly hinders their wide application. Here, we have developed a chaotropic effect-based and photoinduced water-stable supramolecular radical (MB12-2) for efficient antibacterial PTT. The supramolecular radical precursor MB12-1 was constructed by the chaotropic effect between closo-dodecaborate cluster (B12H122-) and N,N'-dimethylated dipyridinium thiazolo [5,4-d] thiazole (MPT2+). Subsequently, with triethanolamine (TEOA) serving as an electron donor, MB12-1 could transform to its radical form MB12-2 through photoinduced electron transfer (PET) under 435-nm laser irradiation. The N2 adsorption-desorption analysis confirmed that MB12-2 was tightly packed through the introduction of B12H122-, which effectively enhanced its stability via a spatial site-blocked effect. Moreover, the half-life of MB12-2 in water was calculated through ultraviolet-visible light (UV-vis) absorption spectra results for periods as long as 20 days. In addition, in the skin infection model, MB12-2, as a wound dressing, showed remarkable photothermal antibacterial activity (>97%) under 660-nm laser irradiation and promoted wound healing. This study presents a simple method for designing long-term water-stable supramolecular radicals, offering a novel avenue for noncontact treatments for bacterial infections.

Monocyte-Derived Macrophages Aggravate Cardiac Dysfunction After Ischemic Stroke in Mice.

BACKGROUND: Cardiac damage induced by ischemic stroke, such as arrhythmia, cardiac dysfunction, and even cardiac arrest, is referred to as cerebral-cardiac syndrome (CCS). Cardiac macrophages are reported to be closely associated with stroke-induced cardiac damage. However, the role of macrophage subsets in CCS is still unclear due to their heterogeneity. Sympathetic nerves play a significant role in regulating macrophages in cardiovascular disease. However, the role of macrophage subsets and sympathetic nerves in CCS is still unclear. METHODS AND RESULTS: In this study, a middle cerebral artery occlusion mouse model was used to simulate ischemic stroke. ECG and echocardiography were used to assess cardiac function. We used Cx3cr1GFPCcr2RFP mice and NLRP3-deficient mice in combination with Smart-seq2 RNA sequencing to confirm the role of macrophage subsets in CCS. We demonstrated that ischemic stroke-induced cardiac damage is characterized by severe cardiac dysfunction and robust infiltration of monocyte-derived macrophages into the heart. Subsequently, we identified that cardiac monocyte-derived macrophages displayed a proinflammatory profile. We also observed that cardiac dysfunction was rescued in ischemic stroke mice by blocking macrophage infiltration using a CCR2 antagonist and NLRP3-deficient mice. In addition, a cardiac sympathetic nerve retrograde tracer and a sympathectomy method were used to explore the relationship between sympathetic nerves and cardiac macrophages. We found that cardiac sympathetic nerves are significantly activated after ischemic stroke, which contributes to the infiltration of monocyte-derived macrophages and subsequent cardiac dysfunction. CONCLUSIONS: Our findings suggest a potential pathogenesis of CCS involving the cardiac sympathetic nerve-monocyte-derived macrophage axis.

Inhibition of PARP1 improves cardiac function after myocardial infarction via up-regulated NLRC5.

The incidence and mortality rate of myocardial infarction are increasing per year in China. The polarization of macrophages towards the classically activated macrophages (M1) phenotype is of utmost importance in the progression of inflammatory stress subsequent to myocardial infarction. Poly (ADP-ribose) polymerase 1(PARP1) is the ubiquitous and best characterized member of the PARP family, which has been reported to support macrophage polarization towards the pro-inflammatory phenotype. Yet, the role of PARP1 in myocardial ischemic injury remains to be elucidated. Here, we demonstrated that a myocardial infarction mouse model induced cardiac damage characterized by cardiac dysfunction and increased PARP1 expression in cardiac macrophages. Inhibition of PARP1 by the PJ34 inhibitors could effectively alleviate M1 macrophage polarization, reduce infarction size, decrease inflammation and rescue the cardiac function post-MI in mice. Mechanistically, the suppression of PARP1 increase NLRC5 gene expression, and thus inhibits the NF-κB pathway, thereby decreasing the production of inflammatory cytokines such as IL-1ß and TNF-α. Inhibition of NLRC5 promote infection by effectively abolishing the influence of this mechanism discussed above. Interestingly, inhibition of NLRC5 promotes cardiac macrophage polarization toward an M1 phenotype but without having major effects on M2 macrophages. Our results demonstrate that inhibition of PARP1 increased NLRC5 gene expression, thereby suppressing M1 polarization, improving cardiac function, decreasing infarct area and attenuating inflammatory injury. The aforementioned findings provide new insights into the proinflammatory mechanisms that drive macrophage polarization following myocardial infarction, thereby introducing novel potential targets for future therapeutic interventions in individuals affected by myocardial infarction.

Hyperglycemia magnifies bupivacaine-induced cell apoptosis triggered by mitochondria dysfunction and endoplasmic reticulum stress.

Nerve cell injury associated with apoptosis plays an important role in the development of diabetic peripheral neuropathy (DPN). However, it remains unclear whether preexisting or potential neurocyte damage induced by hyperglycemia increases sensitivity to local anesthetics. SH-SY5Y cells were pretreated with a high concentration of glucose in vitro, to imitate DPN prior to administration of bupivacaine or placebo. Cell viability and apoptosis were investigated with a CCK-8 assay and flow cytometry, respectively. In addition, mitochondrial membrane potential, reactive oxygen species (ROS), mitochondrially generated ROS, and activity of mitochondrial complexes I and III were studied to explore the molecular mechanism of bupivacaine-induced mitochondrial injury. Grp78 and caspase-12 expression were measured by qRT-PCR and Western blot, representing endoplasmic reticulum (ER) stress. Cell structure was also assessed via transmission electron microscopy. Incubation with bupivacaine decreased the activity of mitochondrial complexes I and III; increased ROS production at cell and mitochondrial levels, mitochondrial potential depolarization, and Grp78 and caspase-12 expression at both transcription and translation levels; and affected cell structure, which could be enhanced by glucose pretreatment. These findings indicate that mitochondrial dysfunction and ER stress related to ROS are involved in bupivacaine-induced apoptosis and may be enhanced by glucose administration.

Nicotinamide adenine dinucleotide (NAD+) repletion attenuates bupivacaine-induced neurotoxicity.

Bupivacaine is one of the most toxic local anesthetics but the mechanisms underlying its neurotoxicity are still unclear. Intracellular nicotinamide adenine dinucleotide (NAD(+)) depletion has been demonstrated to play an essential role in neuronal injury. In the present study, we investigated whether intracellular NAD(+) depletion contributes to bupivacaine-induced neuronal injury and whether NAD(+) repletion attenuates the injury in SH-SY5Y cells. First, we evaluated the intracellular NAD(+) content after bupivacaine exposure. We also examined the cellular NAD(+) level after pretreatment with exogenous NAD(+). We next determined cell viability and the apoptosis rate after bupivacaine treatment in the presence or absence of NAD(+) incubation. Finally, cell injuries such as nuclear injury, reactive oxygen species (ROS) production, and mitochondrial depolarization were detected after bupivacaine treatment with or without NAD(+) pretreatment. Bupivacaine caused intracellular NAD(+) depletion in a time- and concentration-dependent manner. Cellular NAD(+) replenishment prevented cell death and apoptosis induced by bupivacaine. Importantly, exogenous NAD(+) attenuated bupivacaine-induced nuclear injury, ROS production, and mitochondrial depolarization. Our results suggest that NAD(+) depletion is necessary for bupivacaine-induced neuronal necrosis and apoptosis, and that NAD(+) repletion attenuates neurotoxicity resulting from bupivacaine-treatment.

Fentanyl inhibits cell invasion and migration by modulating NF-κB activation in glioma.

Fentanyl is widely used for anesthesia and analgesia in cancer patients. Recent studies have revealed its anti-growth effect in several categories of cancer. Gliomas are the most common primary tumors in the central nervous system with poor prognosis. To investigate the effects of fentanyl on gliomas, glioma cells were treated with different concentrations of fentanyl both in vitro and in vivo. Consequences of proliferation and invasive phenotypes, and related protein expression were evaluated in two human glioma cell lines (U251 and U87). Naloxone, Mu Opioid Receptor (MOR) antagonist, was introduced into culture media to assess the involvement of MOR in Fentanyl-mediated changes. When compared with control group, it could be found that Fentanyl inhibited function of glioma cells only at high concentrations. Western blot and immunofluorescence results revealed that Fentanyl exerted its action via modulating NF-κB (P65) activation which is likely independent of MOR. Moreover, overexpression of P65 by transfection P65-expressing vector restored the invasion and migration of glioma cells, which were inhibited by Fentanyl. In summary, this study showed that opioid pain medication Fentanyl was capable of decreasing invasiveness of glioma cells at a high concentration both in vitro and in vivo, likely via modulating P65 activation.

Intrathecal rapamycin attenuates the mechanical hyperalgesia of paclitaxel-induced peripheral neuropathy in mice.

Paclitaxel is an extensively used chemotherapy antitumor drug and paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common side effect. Rapamycin, originally used as an adjuvant drug for chemotherapy, has recently been found to possess potential neuroprotective activities. Our purposes of this study are to verify the effect of rapamycin on PIPN, which contributes to a new target for PIPN treatment. Mice were given paclitaxel or rapamycin with different injection methods. Paw withdrawal threshold was tested at different time points for mechanical sensitivity assessment. Administration of paclitaxel, both 2 mg/kg and 5 mg/kg, could induce mechanical hypersensitivity. 0.01 mg intrathecal injection of rapamycin showed the best effect on attenuate the mechanical hyperalgesia of PIPN. Intrathecal injection of only rapamycin would not induce the mechanical hyperalgesia while when rapamycin and paclitaxel were used together the mechanical hyperalgesia induced by paclitaxel could be attenuated. Paclitaxel could induce mechanical hyperalgesia in mice and rapamycin could attenuate such mechanical hyperalgesia of PIPN.

Chaotropic Effect-Induced Self-Assembly of the Malachite Green and Boron Cluster for Toxicity Regulation and Photothermal Therapy.

Malachite green (MG), a toxic antibacterial agent, is widely used in the farming industry. Effectively regulating the biotoxicity of this highly water-soluble cationic dye is challenging. Here, we present a novel strategy to reduce the biotoxicity of MG through the self-assembly of MG and the closo-dodecaborate cluster ([B12H12]2-) driven by the chaotropic effect. [B12H12]2- and MG in an aqueous solution can rapidly form an insoluble cubic-type supramolecular complex (B12-MG), and the original toxicity of MG is completely suppressed. Surprisingly, this supramolecular complex, B12-MG, has a strong UV-vis absorption peak at 600-800 nm and significant photothermal conversion efficiency under 660 nm laser irradiation. On this basis, B12-MG, the supramolecular complex, can be used as an efficient photothermal agent for antimicrobial photothermal therapy (PTT) both in vitro and in vivo. As a molecular chaperone of MG, [B12H12]2- not only can be applied as an antidote to regulate the biotoxicity of MG but also provides a novel method for the construction of photothermal agents for PTT based on the chaotropic effect.