Homoharringtonine enhances cytarabine-induced apoptosis in acute myeloid leukaemia by regulating the p38 MAPK/H2AX/Mcl-1 axis.

Acute myeloid leukaemia (AML) is a fatal haematopoietic malignancy and is treated with the conventional combination of cytarabine (Ara-C) and daunorubicin (Dau). The survival rate of AML patients is lower due to the cardiotoxicity of daunorubicin. Clinically, homoharringtonine (HHT) plus Ara-C has been reported to be equally effective as Dau plus Ara-C in some types of AML patients with less toxic effects. We utilized the clinical use of homoharringtonine in combination with Ara-C to test its combination mechanism. We found that the insensitivity of AML cells to cytarabine-induced apoptosis is associated with increased Mcl-1 stability and p38 inactivation. HHT downregulates Mcl-1, phosphorylates H2AX and induces apoptosis by activating p38 MAPK. Inactivation of p38 through inhibitors and siRNA blocks apoptosis, H2AX phosphorylation and Mcl-1 reduction. HHT enhances Ara-C activation of the p38 MAPK signalling pathway, overcoming Ara-C tolerance to cell apoptosis by regulating the p38/H2AX/Mcl-1 axis. The optimal ratio of HHT to Ara-C for synergistic lethality in AML cells is 1:4 (M/M). HHT synergistically induces apoptosis in combination with Ara-C in vitro and prolongs the survival of xenografts. We provide a new mechanism for AML treatment by regulating the p38 MAPK/H2AX/Mcl-1 axis to improve cytarabine therapy.

Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

Chondroitin sulfate-modified tragacanth gum-gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses,  and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum-gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum-gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1ß, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.

Achieving broad availability of SARS-CoV-2 detections via smartphone-based analysis.

With the development of COVID-19, widely available tests are in great demand. Naked-eye SARS-CoV-2 test kits have recently been developed as home tests, but their sensitivity and accuracy are sometimes limited. Smartphones can convert various signals into digital information, potentially improving the sensitivity and accuracy of these home tests. Herein, we summarize smartphone-based detections for SARS-CoV-2. Optical detections of non-nucleic acids using various sensors and portable imaging systems, as well as nucleic acid analyses based on LAMP, CRISP, CATCH, and biosensors are discussed. Furthermore, different electrochemical detections were compared. We show results obtained using relatively complex equipment, complicated programming procedures, or custom smartphone apps, and describe methods for obtaining information with only simple setups and free software on smartphones. Then, the combined costs of typical smartphone-based detections are evaluated. Finally, the prospect of improving smartphone-based strategies to achieve broad availability of SARS-CoV-2 detection is proposed.

Zinc Promotes Spinal Cord Injury Recovery by Blocking the Activation of NLRP3 Inflammasome Through SIRT3-Mediated Autophagy.

Spinal cord injuries (SCI) are complex and cause complex neurological disorders with serious implications for the health of society. Excessive neuroinflammation is one of the pathogenesis of trauma-related central nervous system (CNS) dysfunction. The initiation of inflammatory response mainly stems from neuronal necrosis in the central nervous system. The therapeutic effects and underlying mechanisms of zinc targeting neurons were investigated in vivo and in vitro using protein chips, western blotting, reactive oxygen species (ROS) activity assays, ELISA, RT-qPCR, and immunostaining. In this study, we found that zinc promotes functional recovery. Specifically, we found that zinc increased neuronal survival and suppressed lesion size and focal apoptosis levels in vivo. Zinc administration confers neuroprotection by inhibiting NLRP3 inflammasome-associated cytokine levels probed with a protein chip. Furthermore, we found that zinc promoted SIRT3-mediated induction of autophagy, which abrogated inflammatory responses and mitochondrial ROS production in the injured spinal cord and cultured neurons. These findings suggest that zinc improves neuroinflammation and improves dyskinesia after SCI. In conclusion, zinc may be a potential therapeutic immunomodulatory challenge for the treatment of trauma-related CNS dysfunction.

Curcumin-Loaded Macrophage-Derived Exosomes Effectively Improve Wound Healing.

This study aims to investigate the potential therapeutic effect of exosomes derived from macrophages loaded with curcumin (Exos-cur) on the healing of diabetic wounds. As a new type of biomaterial, Exos-cur has better stability, anti-inflammation, and antioxidation biological activity. In in vitro experiments, Exos-cur can promote the proliferation, migration, and angiogenesis of HUVECs (human umbilical vein endothelial cells) while reducing the ROS (reactive oxygen species) produced by HUVECs induced by high glucose, regulating the mitochondrial membrane potential, reducing cell oxidative damage, and inhibiting oxidative stress and inflammation. In the in vivo experiment, the Exos-cur treatment group had an increased percentage of wound closure and contraction compared with the diabetic wound control group. Hematoxylin-eosin staining (HE) and Masson staining showed that the Exos-cur treatment group had more advanced re-epithelialization, and the generated mature granulation tissue was rich in a large number of capillaries and newly deposited collagen fibers. Western blot and immunofluorescence analyses showed that Exos-cur can inhibit inflammation by activating the Nrf2/ARE pathway, upregulate the expression of wound healing-related molecules, promote angiogenesis, and accelerate wound healing in diabetic rats. These results show that Exos-cur has a good therapeutic effect on diabetic skin defects and provide experimental evidence for the potential clinical benefits of Exos-cur.

Zinc Promotes Microglial Autophagy Through NLRP3 Inflammasome Inactivation via XIST/miR-374a-5p Axis in Spinal Cord Injury.

Zinc has reported to play a neuroprotective role in the development of spinal cord injury (SCI). The protective mechanism of zinc remains to be uncovered. The aim of the current study was to investigate the neuroprotective mechanism of zinc in the progression of SCI. The C57BL/6J mouse SCI model was established to confirm the protective role of zinc in vivo, while the cellular model was induced in mouse microglial BV2 cells by using lipopolysaccharide (LPS). The expression levels of XIST, miR-374a-5p and NLRP3 inflammasome as well as the autophagy-related proteins were detected using real-time PCR and immunoblotting. Cell viability was assessed by CCK-8 assay. Apoptosis was evaluated by TUNEL staining, flow cytometry, the determination of apoptosis-related proteins. The target relationship was confirmed by luciferase reporter assays. Zinc improved locomotor function in SCI mice and alleviated LPS-induced BV2 cell injuries by inhibiting apoptosis and initiating autophagy processes. XIST and NLRP3 inflammasome was upregulated while miR-374a-5p was downregulated in spinal cords of SCI mice and LPS-treated BV2 cells. All these effects were inhibited by Zinc treatment. XIST knockdown triggered microglial autophagy-mediated NLRP3 inactivation in LPS-induced BV2 cells by regulating miR-374a-5p. Zinc treatment protected BV2 cells from LPS-induced cell injury by the downregulation of XIST. This process might be through autophagy­mediated NLRP3 inflammasome inactivation by targeting miR-374a-5p. Zinc downregulates XIST and induces neuroprotective effects against SCI by promoting microglial autophagy-induced NLRP3 inflammasome inactivation through regulating miR-374a-5p. Our finding provides novel opportunities for the understanding of zinc-related therapy of SCI.

Prospects of NIR fluorescent nanosensors for green detection of SARS-CoV-2.

The pandemic of the novel coronavirus disease 2019 (COVID-19) is continuously causing hazards for the world. Effective detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can relieve the impact, but various toxic chemicals are also released into the environment. Fluorescence sensors offer a facile analytical strategy. During fluorescence sensing, biological samples such as tissues and body fluids have autofluorescence, giving false-positive/negative results because of the interferences. Fluorescence near-infrared (NIR) nanosensors can be designed from low-toxic materials with insignificant background signals. Although this research is still in its infancy, further developments in this field have the potential for sustainable detection of SARS-CoV-2. Herein, we summarize the reported NIR fluorescent nanosensors with the potential to detect SARS-CoV-2. The green synthesis of NIR fluorescent nanomaterials, environmentally compatible sensing strategies, and possible methods to reduce the testing frequencies are discussed. Further optimization strategies for developing NIR fluorescent nanosensors to facilitate greener diagnostics of SARS-CoV-2 for pandemic control are proposed.

Triamcinolone acetonide-loaded nanoparticles encapsulated by CD90+ MCSs-derived microvesicles drive anti-inflammatory properties and promote cartilage regeneration after osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a highly prevalent human degenerative joint disorder that has long plagued patients. Glucocorticoid injection into the intra-articular (IA) cavity provides potential short-term analgesia and anti-inflammatory effects, but long-term IA injections cause loss of cartilage. Synovial mesenchymal stem cells (MSCs) reportedly promote cartilage proliferation and increase cartilage content. METHODS: CD90+ MCS-derived micro-vesicle (CD90@MV)-coated nanoparticle (CD90@NP) was developed. CD90+ MCSs were extracted from human synovial tissue. Cytochalasin B (CB) relaxed the interaction between the cytoskeleton and the cell membranes of the CD90+ MCSs, stimulating CD90@MV secretion. Poly (lactic-co-glycolic acid) (PLGA) nanoparticle was coated with CD90@MV, and a model glucocorticoid, triamcinolone acetonide (TA), was encapsulated in the CD90@NP (T-CD90@NP). The chondroprotective effect of T-CD90@NP was validated in rabbit and rat OA models. RESULTS: The CD90@MV membrane proteins were similar to that of CD90+ MCSs, indicating that CD90@MV bio-activity was similar to the cartilage proliferation-inducing CD90+ MCSs. CD90@NP binding to injured primary cartilage cells was significantly stronger than to erythrocyte membrane-coated nanoparticles (RNP). In the rabbit OA model, the long-term IA treatment with T-CD90@NP showed significantly enhanced repair of damaged cartilage compared to TA and CD90+ MCS treatments. In the rat OA model, the short-term IA treatment with T-CD90@NP showed effective anti-inflammatory ability similar to that of TA treatment. Moreover, the long-term IA treatment with T-CD90@NP induced cartilage to restart the cell cycle and reduced cartilage apoptosis. T-CD90@NP promoted the regeneration of chondrocytes, reduced apoptosis via the FOXO pathway, and influenced type 2 macrophage polarization to regulate inflammation through IL-10. CONCLUSION: This study confirmed that T-CD90@NP promoted chondrocyte proliferation and anti-inflammation, improving the effects of a clinical glucocorticoid treatment plan.

Metformin alleviates high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKα in rat astrocytes.

Hyperglycemia-induced endoplasmic reticulum (ER) stress and inflammatory response afflict neuropathological diseases (such as epilepsy and Alzheimer's disease). Astrocytes are the critical cells that mediate brain inflammation in this process. Metformin is a kind of hypoglycemic drugs widely used in clinical practice, which has anti-inflammatory and antioxidant effects. However, the biological mechanism of metformin in regulating inflammation and ER stress induced by hyperglycemia remains unclear. Therefore, in this study, rat primary astrocytes were preincubated with metformin and AMPK agonist AICAR for 1 h prior to administration of high glucose (33 mM glucose). Our findings indicated that metformin treatment inhibited the elevated ER stress and inflammation in high glucose-treated astrocytes. Moreover, metformin inhibited the formation of caveolin1/AMPKα complex. Additionally, the effects of AICAR on astrocytes were similar to metformin. In conclusion, metformin reduced high glucose-induced ER stress and inflammation by inhibiting the interaction between caveolin1 and AMPKα, suggesting that the caveolin1/AMPKα complex may be a potential therapeutic target for metformin.

Therapy of spinal cord injury by zinc modified gold nanoclusters via immune-suppressing strategies.

BACKGROUND: Spinal cord injury (SCI) is damage to the central nervous system (CNS) that causes devastating complications from chronic pain to breathing problems. Unfortunately, few effective and safe treatments are known to relieve the damages of SCI. Nanomedicines are used for the treatment of SCI with relatively few side effects, but only depending on the delivery of additional drugs, which increase complexity to the treatment. Considering the urgent need for saving SCI patients, it is important to develop promising nanobiotechnology for relieving their pains. METHODS: The clinical survey was used to investigate SCI patients, thereafter the therapy plan was designed. The receiver-operating characteristics (ROC) curves of the prediction model were built to find symptoms after SCI. The treatment plan (i.e. immunosuppressive strategy) was designed by manufacturing therapies based on gold nanoclusters (AuNCs). The response of the immune cells (macrophages) was studied accordingly. The western blot, reactive oxygen species (ROS) activity assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (RT-qPCR), and immunochemical staining were used for evaluation of the in vivo and in vitro therapeutic effects. RESULTS: We found increased monocytes/macrophages (M/Ms) levels in 114 SCI subjects (44.7% with severe SCI complications) by the clinical survey. Additionally, the enhanced macrophage level was found to be closely related to the walking disorder after SCI. Since macrophages were central effector cells of the immune system, we assumed that the immune-suppressing strategies could be used for SCI therapy. Thereafter, AuNCs were stabilized by dihydrolipoic acid (DHLA) enantiomers (including DL-DHLA, R-DHLA; A racemic mixture (R and S) was denoted as DL; R and S refer to Rectus and Sinister), obtaining DL-DHLA-AuNCs and R-DHLA-AuNCs, respectively. In addition, zinc-modified DL-DHLA and R-DHLA stabilized AuNCs (i.e., DL-DHLA-AuNCs-Zn and R-DHLA-AuNCs-Zn) were investigated. Among these AuNCs, R-DHLA-AuNCs-Zn showed the most remarkable therapeutic effect for promoting the polarization of pro-inflammatory macrophages and reducing neuronal ROS-induced apoptosis and inflammation in vitro and in vivo; the lesion size was decreased and the survival rate of ventral neurons is higher. CONCLUSIONS: R-DHLA-AuNCs-Zn have comprehensive therapeutic capabilities, especially the immune-suppressing effects for the therapy of SCI, which is promising to relieve the pain or even recover SCI for the patients.

Tea polyphenol modified, photothermal responsive and ROS generative black phosphorus quantum dots as nanoplatforms for promoting MRSA infected wounds healing in diabetic rats.

BACKGROUND: Healing of MRSA (methicillin-resistant Staphylococcus aureus) infected deep burn wounds (MIDBW) in diabetic patients remains an obstacle but is a cutting-edge research problem in clinical science. Surgical debridement and continuous antibiotic use remain the primary clinical treatment for MIDBW. However, suboptimal pharmacokinetics and high doses of antibiotics often cause serious side effects such as fatal complications of drug-resistant bacterial infections. MRSA, which causes wound infection, is currently a bacterium of concern in diabetic wound healing. In more severe cases, it can even lead to amputation of the patient's limb. The development of bioactive nanomaterials that can promote infected wound healing is significant. RESULTS: The present work proposed a strategy of using EGCG (Epigallocatechin gallate) modified black phosphorus quantum dots (BPQDs) as therapeutic nanoplatforms for MIDBW to achieve the synergistic functions of NIR (near-infrared)-response, ROS-generation, sterilization, and promoting wound healing. The electron spin resonance results revealed that EGCG-BPQDs@H had a more vital photocatalytic ability to produce singlet oxygen than BPQDs@H. The inhibition results indicated an effective bactericidal rate of 88.6% against MRSA. Molecular biology analysis demonstrated that EGCG-BPQDs significantly upregulated CD31 nearly fourfold and basic fibroblast growth factor (bFGF) nearly twofold, which were beneficial for promoting the proliferation of vascular endothelial cells and skin epidermal cells. Under NIR irradiation, EGCG-BPQDs hydrogel (EGCG-BPQDs@H) treated MIDBW area could rapidly raise temperature up to 55 °C for sterilization. The MIBDW closure rate of rats after 21 days of treatment was 92.4%, much better than that of 61.1% of the control group. The engineered EGCG-BPQDs@H were found to promote MIDBW healing by triggering the PI3K/AKT and ERK1/2 signaling pathways, which could enhance cell proliferation and differentiation. In addition, intravenous circulation experiment showed good biocompatibility of EGCG-BPQDs@H. No significant damage to major organs was observed in rats. CONCLUSIONS: The obtained results demonstrated that EGCG-BPQDs@H achieved the synergistic functions of photocatalytic property, photothermal effects and promoted wound healing, and are promising multifunctional nanoplatforms for MIDBW healing in diabetics.

Metformin alleviates hydrogen peroxide-induced inflammation and oxidative stress via inhibiting P2X7R signaling in spinal cord tissue cells neurons.

Metformin, the first medication that is often prescribed for the treatment of type 2 diabetes mellitus, was recently found to be neuroprotective. To study the mechanism underlying the neuroprotective effect of metformin, we pretreated primary spinal cord neurons with 50 µM or 100 µM metformin for 2 h prior to treatment with hydrogen peroxide (H2O2) for up to 48 h. Our results showed that H2O2 increased the expression of purinergic receptor P2X7 (P2X7R) in spinal cord neurons, which promoted the downstream pro-inflammatory cytokines release and oxidative stress. We found that metformin could reverse these pro-inflammatory and pro-oxidative effects of H2O2. Besides, P2X7R knockdown by siRNA suppressed H2O2-induced pro-inflammatory cytokine release and oxidative stress response. In conclusion, our results show that metformin can alleviate H2O2-induced inflammation and oxidative stress via modulating the P2X7R signaling pathway.

Engineered extracellular vesicles derived from primary M2 macrophages with anti-inflammatory and neuroprotective properties for the treatment of spinal cord injury.

BACKGROUND: Uncontrollable inflammation and nerve cell apoptosis are the most destructive pathological response after spinal cord injury (SCI). So, inflammation suppression combined with neuroprotection is one of the most promising strategies to treat SCI. Engineered extracellular vesicles with anti-inflammatory and neuroprotective properties are promising candidates for implementing these strategies for the treatment of SCI. RESULTS: By combining nerve growth factor (NGF) and curcumin (Cur), we prepared stable engineered extracellular vesicles of approximately 120 nm from primary M2 macrophages with anti-inflammatory and neuroprotective properties (Cur@EVs-cl-NGF). Notably, NGF was coupled with EVs by matrix metalloproteinase 9 (MMP9)-a cleavable linker to release at the injured site accurately. Through targeted experiments, we found that these extracellular vesicles could actively and effectively accumulate at the injured site of SCI mice, which greatly improved the bioavailability of the drugs. Subsequently, Cur@EVs-cl-NGF reached the injured site and could effectively inhibit the uncontrollable inflammatory response to protect the spinal cord from secondary damage; in addition, Cur@EVs-cl-NGF could release NGF into the microenvironment in time to exert a neuroprotective effect against nerve cell damage. CONCLUSIONS: A series of in vivo and in vitro experiments showed that the engineered extracellular vesicles significantly improved the microenvironment after injury and promoted the recovery of motor function after SCI. We provide a new method for inflammation suppression combined with neuroprotective strategies to treat SCI.

Diagnosis of cancer at early stages based on the multiplex detection of tumor markers using metal nanoclusters.

Traditional cancer diagnosis strategies are not considered by most people until the last resort, which delays many cancer treatments leading to advanced stages. Tumor marker sensors show great potential for detecting cancer because of its cost-effective and harmless checking procedures. Normally, one tumor marker is detected each time by using one type of sensor, but the accuracy to declare cancer is not always satisfied. Metal nanoclusters are ultra-small nanomaterials with low toxicity, distinct optical properties, catalytic activities, and cost-effective performance. Some metal nanoclusters have been designed to detect more than one tumor marker in a single step. The consideration of combined parameters using such facile sensing strategies has the potential to simplify the test procedure, and increase the diagnostic accuracy of early cancer. Therefore, various sensing strategies for the multiplex detection of tumor markers using metal nanoclusters are summarized.

Role of NLRP3 Inflammasomes in Neuroinflammation Diseases.

BACKGROUND: Inflammasomes are large intracellular multi-protein signaling complexes that are formed in the cytosolic compartment as an inflammatory immune response to endogenous danger signals. The formation of the inflammasome enables activation of an inflammatory protease caspase-1 and pyroptosis initiation with the subsequent cleaving of the pro-inflammatory cytokines interleukin (IL)-1ß and proIL-18 to produce active forms. The inflammasome complex consists of a nod-like receptor, the adapter apoptosis-associated speck-like protein, and caspase-1. Dysregulation of NLRP3 inflammasome activation is involved in neuroinflammation disease pathogenesis, although its role in SCI development and progression remains controversial due to the inconsistent findings described. SUMMARY: In this review, we summarize the current knowledge on the contribution of the NLRP3 inflammasome on potential neuroinflammation diseases therapy.

Toxicity of food sweetener-sodium cyclamate on osteoblasts cells.

In this paper, the effect of commonly used food sweetener (sodium cyclamate) on the proliferation and differentiation of osteoblasts has been researched. The morophology change of osteoblasts was investigated by confocal laser scanning microscopy. Cell viability was studied by MTT analysis. BMP2 expression was analyzed by western blot and immunofluorescence. Mineralization ability of osteoblasts was researched by using alizarin red staining method. The results indicate that a very low concentration (0.06 µM) of sodium cyclamate can curle and fold microfilament and microtubule of osteoblasts. The increase addition of sodium cyclamate resulted significantly decrease of cells viability. The expression of bone morphogenetic protein-2 (BMP2) was seriously suppressed by sodium cyclamate. Alizarin Red staining experiment revealed that sodium cyclamate decreased the mineralization ability of osteoblasts. The present results suggest that sodium cyclamate can seriously inhibit the proliferation and differentiation of osteoblasts.

Melatonin Enhances Autophagy and Reduces Apoptosis to Promote Locomotor Recovery in Spinal Cord Injury via the PI3K/AKT/mTOR Signaling Pathway.

Spinal cord injury (SCI) leads to neuronal death resulting in central nervous system (CNS) dysfunction; however, the pathogenesis is still poorly understood. Melatonin (MT), a hormone secreted mainly by the pineal gland, is associated with neuroprotective effects against SCI. Enhanced autophagy can promote the recovery of locomotor function and reduce apoptosis after SCI. Interestingly, MT increases autophagy in SCI in vivo. Nevertheless, the ability of MT to increase autophagy and decrease apoptosis, and the potential effects on the recovery of motor neurons in the anterior horn after SCI remain to be clarified. In this study, we discovered that MT treatment improved motor function recovery in a rat SCI model. Indeed, MT upregulated the expression of the phosphatidylinositol 3-kinase (PI3K), while expression of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) was downregulated after SCI. Additionally, MT increased the expression of autophagy-activating proteins, while the expression of apoptosis-activating proteins in neurons was decreased following SCI. Furthermore, autophagy was inhibited, while apoptosis was induced in SCI model rats and lipopolysaccharide (LPS)-stimulated primary neurons by treatment with MT, the PI3K inhibitor 3-methyladenine (3-MA) and mTOR inhibitor Rapamycin (Rapa). Collectively, our results suggest that MT can improve the recovery of locomotor function by enhancing autophagy as well as reducing apoptosis after SCI in rats, probably via the PI3K/AKT/mTOR signaling pathway.

Silver Nanoclusters Encapsulated into Metal-Organic Frameworks for Rapid Removal of Heavy Metal Ions from Water.

Metal nanomaterials have been reported as effective absorbents for the removal of pollutants in the water system, but the release of ions from these nanomaterials brings another concern. Herein, silver nanoclusters (AgNCs) were encapsulated in porous metal-organic frameworks of ZIF-8 (MOF-AgNCs). Compared to AgNCs, the release of Ag+ significantly decreases from MOF-AgNCs, indicating that the product presents a lower threat to the environment. The MOF-AgNCs were employed for the rapid removal of heavy metals, such as Pb2+ and Mn2+, from water. The mechanism and removal efficiencies were investigated.

Receptor for Advanced Glycation End-Products (RAGE) Blockade Do Damage to Neuronal Survival via Disrupting Wnt/ß-Catenin Signaling in Spinal Cord Injury.

Wnt signaling are recognized key factors in neuronal development, cell proliferation and axonal guidance. However, RAGE effect on wnt signaling after spinal cord injury (SCI) are poorly understood. Our study aims to explore RAGE blockade effect on wnt signaling after SCI. We constructed Allen SCI model and micro-injected with RAGE neutralizing antibody or IgG after injury. We determined ß-catenin, wnt3a and its receptor frizzled-5 via Western blot. We determined ß-catenin/NeuN expression at 2 weeks after SCI via immunofluorescence (IF). We found that ß-catenin, wnt3a and wnt receptor frizzled5 expression were activated after SCI at 3 days after injury. However, RAGE blockade inhibit ß-catenin, wnt3a and frizzled5 expression. We found that ß-catenin accumulation in NeuN cells were activated after SCI via IF, however, RAGE blockade reduced ß-catenin and NeuN positive cells. RAGE blockade attenuated number of survived neurons and decreased area of spared white matter around the epicenter. RAGE signaling may involved in disrupting wnt signaling to aids neuronal recovery after SCI.