Gentiopicroside promotes the osteogenesis of bone mesenchymal stem cells by modulation of ß-catenin-BMP2 signalling pathway.

Osteoporosis is characterized by increased bone fragility, and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN), a class of natural compounds with numerous biological activities such as anti-resorptive properties and protective effects against bone loss. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy. In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, whereas in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months. Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and up-regulated the osteogenic factors (Runx2, OSX, OCN, OPN and BMP2). In vivo, GEN promoted the expression of Runx2, OCN and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/ß-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/ß-catenin inhibitor DKK1. Silencing the ß-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only ß-catenin was silenced, although the knockout of BMP2 did not affect ß-catenin expression induced by GEN. Therefore, GEN promotes BMSC osteogenesis by regulating ß-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.

The immuno-reactivity of polypseudorotaxane functionalized magnetic CDMNP-PEG-CD nanoparticles.

pH-magnetic dual-responsive nanocomposites have been widely used in drug delivery and gene therapy. Recently, a polypseudorotaxane functionalized magnetic nanoparticle (MNP) was developed by synthesizing the magnetic nanoparticles with cyclodextrin (CD) molecules (CDMNP) via polyethylene glycol (PEG) (CDMNP-PEG-CD). The purpose of this study was to explore the antigenicity and immunogenicity of the nanoparticles in vivo prior to their further application explorations. Here, nanoparticles were assessed in vivo for retention, bio-distribution and immuno-reactivity. The results showed that, once administered intravenously, CDMNP-PEG-CD induced a temporary blood monocyte response and was cleared effectively from the body through the urine system in mice. The introduction of ß-CD and PEG/ß-CD polypseudorotaxane on SiO2 magnetic nanoparticles (SOMNP) limited particle intramuscular dispersion after being injected into mouse gastrocnemius muscle (GN), which led to the prolonged local inflammation and muscle toxicity by CDMNP and CDMNP-PEG-CD. In addition, T cells were found to be more susceptible for ß-CD-modified CDMNP; however, polypseudorotaxane modification partially attenuated ß-CD-induced T cell response in the implanted muscle. Our results suggested that CDMNP-PEG-CD nanoparticles or the decomposition components have potential to prime antigen-presenting cells and to break the muscle autoimmune tolerance.

Transanal and transabdominal combined endoscopic resection of rectal stenosis and anal reconstruction based on transanal endoscopic technique.

OBJECTIVE: To propose a method for the resection of the rectal anastomotic stenosis and anal reconstruction based on the transanal endoscopic technique through a transanal and transabdominal combined endoscopic resection, and to verify its clinical effectiveness. METHODS: Thirty-eight patients with anastomotic stenosis were admitted to the Sixth Affiliated Hospital, Sun Yat-sen University, China, from January 2016 to September 2019. Patients were divided into an experimental group (17 patients) and a control group (21 patients) subjected to the removal of the intestinal stenosis followed by anal reconstruction, they underwent transanal and transabdominal endoscopic surgery and traditional transabdominal surgery, respectively. Data on intraoperative blood loss, operation time, postoperative recovery, and prognosis were collected. RESULTS: (1) The median intraoperative blood loss was approximately 100 ml, without conversion to laparotomy during the surgery and intraoperative complications. The safety of the surgical operation was improved. (2) The operation time was shortened compared to previous reports, and the median operative time was 193 min. The average time of transanal endoscopic dissociation to the retroperitoneal fold was 76 min. (3) Laparoscopic assistance was carried out on 14 of the17 patients, and the incision was reduced. (4) The short-term curative effect was quite satisfactory, without permanent stoma. The average time to recover food intake after the surgery was 1.5 days. The average ambulation time was 3 days. Within 30 days after the surgery, one case suffered anastomotic leakage and then underwent refunctioning stoma through a second surgery. One patient suffered from intestinal obstruction, and the condition was improved through a conservative treatment. One case experienced delayed abdominal wound healing. CONCLUSION: The transanal and transabdominal endoscopic resection of the rectal anastomotic stenosis and anal reconstruction reduced the difficulty of the surgery, improved its safety, shortened the operation time, decreased the operative complications, and enabled patients to recover well after surgery.

Injectable gelatin microspheres loaded with platelet rich plasma improve wound healing by regulating early inflammation.

We investigated the potential of gelatin microspheres (GMs) loaded with platelet-rich plasma (PRP) to enhance their wound healing effect. Platelets from the PRP were immobilized onto GMs to form biomimetic bioreactor GM+PRP. The therapeutic effect of this agent was further investigated in vivo on a wound-healing model in rats. Wounds were locally injected with phosphate buffered saline (PBS), GM, PRP, and GM+PRP. Wound healing rate, vessel density, and inflammation level were measured histologically, by RT-PCR, and by Western blotting at days 3, 7, 14, and 21. Platelets on GM caused a continuous high release in both interleukin-10 and metalloproteinase-3 compared with PRP alone. Both GM+PRP and PRP successfully accelerated the wound healing process, while GM alone did not improve the wound healing process compared with the untreated control. Wounds treated with GM+PRP resulted in shorter healing period and improved dermal structure. GM+PRP improved angiogenesis in the wound by increasing expression of angiogenic factors. GM+PRP prolonged and enhanced the cytokine release profile compared with PRP. By promoting the inflammatory and angiogenic responses, GM+PRP has the potential to improve wound healing. Our findings demonstrate that GMs are an injectable carrier that enhanced the therapeutic effects of PRP.

Bmi deficiency causes oxidative stress and intervertebral disc degeneration which can be alleviated by antioxidant treatment.

The transcriptional repressor Bmi-1 is involved in cell-cycle regulation and cell senescence, the deficiency of which has been shown to cause oxidative stress. This study investigated whether Bmi-1 deficiency plays a role in promoting disc degeneration and the effect of treatment with antioxidant N-acetylcysteine (NAC) on intervertebral disc degeneration. Bmi-1-/- mice were treated with the antioxidant NAC, supplied in drinking water (Bmi-1-/- +NAC). For in vitro experiments, mouse intervertebral discs were cultured under low oxygen tension and serum-limiting conditions in the presence of tumour necrosis factor α and interleukin 1ß in order to mimic degenerative insult. Disc metabolism parameters in these in vitro and in vivo studies were evaluated by histopathological, immunohistochemical and molecular methods. Bmi-1-/- mice showed lower collagen Ⅱ and aggrecan levels and higher collagen Ⅹ levels than wild-type and Bmi-1-/- +NAC mice. Bmi-1-/- mice showed significantly lower superoxide dismutase (SOD)-1, SOD-2, glutathione peroxidase (GPX)-1 and GPX-3 levels than their wild-type littermates and Bmi-1-/- + NAC mice. Relative to Bmi-1-/- mice, the control and Bmi-1-/- +NAC mice showed significantly lower p16, p21, and p53 levels. These results demonstrate that Bmi-1 plays an important role in attenuating intervertebral disc degeneration in mice by inhibiting oxidative stress and cell apoptosis.

Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR-4/NF-κB and AMPK/Nrf2 signalling pathways.

The purpose of this study was to alleviate liver disturbance by applying polysaccharides from Dicliptera chinensis (DCP) to act on the adenosine monophosphate-activated protein kinase/ nuclear factor erythroid 2-related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll-like receptor 4 (TLR-4)/ nuclear factor kappa-B (NF-κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR-4 knockout (-/- ) mice. For this, we evaluated the expression levels of SREBP-1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR-4/ NF-κB inflammatory pathway, DCP inhibits TLR-4, up-regulates the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduces the expression of phospho(p)-NF-κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1ß, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up-regulates the expression of p-AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.

Scoparone alleviates hepatic fibrosis by inhibiting the TLR-4/NF-κB pathway.

The aim of this study was to investigate the role of scoparone (SCO) in hepatic fibrosis. For this, we conducted in vivo and in vitro experiments. In vivo rats that were divided into six groups, control, carbon tetrachloride, and colchicine, as well as SCO groups, SCO50, SCO100, and SCO200 treated with 50, 100, and 200 mg/kg SCO doses, respectively. Furthermore, SCO was shown to inhibit Toll-like receptor-4 (TLR-4)/nuclear factor kappa-B (NF-κB; TLR-4/NF-κB) signals by inhibiting TLR-4, which in turn downregulates the expression of MyD88, promotes NF-κB inhibitor-α, NF-κB inhibitor-ß, and NF-κB inhibitor-ε activation, while inhibiting NF-κB inhibitor-ζ. Subsequently, the decrease of phosphorylation of nuclear factor-κB levels leads to the downregulation of the downstream inflammatory factors' tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 beta, thus weakening hepatic fibrosis. Notably, the SCO200 treated group presented the most significant improvement. Hence, we conclude that SCO alleviates hepatic fibrosis by inhibiting TLR-4/NF-κB signals.

Three-dimensional printing of patient-specific plates for the treatment of acetabular fractures involving quadrilateral plate disruption.

BACKGROUND: Complicated acetabular fractures comprise the most challenging field for orthopedists. The purpose of this study was to develop three-dimensional printed patient-specific (3DPPS) Ti-6Al-4 V plates to treat complicated acetabular fractures involving quadrilateral plate (QLP) disruption and to evaluate their efficacy. METHODS: Fifty patients with acetabular fractures involving QLP disruption were selected between January 2016 and June 2017. Patients were divided into a control group (Group A, 35 patients) and an experimental group (Group B, 15 patients), and were treated by the conventional method of shaping reconstruction plates or with 3DPPS Ti-6AL-4 V plates, respectively. The efficacy of Ti-6AL-4 V plates was evaluated by blood loss, operative time, reduction quality, postoperative residual displacement, and complications. RESULTS: The operative time and blood loss in Group B were reduced compared to Group A, and the difference was statistically significant (P < 0.05). There was no significant difference in reduction quality between the two groups (P > 0.05). Reduction quality in Group B was anatomic in 10 (66.7%), satisfactory in four (26.7%), and poor in one (6.7%). In Group A, they were anatomic in 18 (51.4%), satisfactory in 13 (37.1%), and poor in four (11.4%). Residual displacement in Group B was less than that in Group A, and the difference was statistically significant (P < 0.05). In Group B, one case exhibited loosening of the pubic screw postoperatively. In Group A, there was one case of wound infection, one of deep vein thrombosis (DVT) in the ipsilateral lower limb, one case of traumatic arthritis and two obturator nerve injuries. CONCLUSIONS: The 3DPPS Ti-6AL-4 V plate is a feasible, accurate and effective implant for acetabular fracture treatment.

Calmodulin-dependent signalling pathways are activated and mediate the acute inflammatory response of injured skeletal muscle.

KEY POINTS: There is a close relationship between skeletal muscle physiology and Ca2+ /calmodulin (CaM) signalling. Despite the effects of Ca2+ /CaM signalling on immune and inflammatory responses having been extensively explored, few studies have investigated the role of CaM pathway activation on the post-injury muscle inflammatory response. In this study, we investigated the role of CaM-dependent signalling in muscle inflammation in cardiotoxin induced myoinjuries in mice. The Ca2+ /calmodulin-dependent protein kinase II (CaMII), Ca2+ /calmodulin-dependent protein kinase IV (CaMKIV), and nuclear factor of activated T cells (NFAT) pathways are likely to be simultaneously activated in muscle cells and in infiltrating lymphocytes and to regulate the immune behaviours of myofibres in an inflammatory environment, and these pathways ultimately affect the outcome of muscle inflammation. ABSTRACT: Calcium/calmodulin (Ca2+ /CaM) signalling is essential for immune and inflammatory responses in tissues. However, it is unclear if Ca2+ /CaM signalling interferes with muscle inflammation. Here we investigated the roles of CaM-dependent signalling in muscle inflammation in mice that had acute myoinjuries in the tibialis anterior muscle induced by intramuscular cardiotoxin (CTX) injections and received intraperitoneal injections of either the CaM inhibitor calmidazolium chloride (CCL) or CaM agonist calcium-like peptide 1 (CALP1). Multiple inflammatory parameters, including muscle autoantigens and toll-like receptors, mononuclear cell infiltration, cytokines and chemokines associated with peripheral muscle inflammation, were examined after the injury and treatment. CALP1 treatment enhanced intramuscular infiltration of monocytes/macrophages into the damaged tibialis anterior muscle and up-regulated mRNA and protein levels of muscle autoantigens (Mi-2, HARS and Ku70) and Toll-like receptor 3 (TLR3), and mRNA levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), Monocyte chemoattractant protein-1 (MCP1), Monocyte chemoattractant protein-3 (MCP3) and Macrophage inflammatory protein-1(MIP-1α) in damaged muscle. In contrast, CCL treatment decreased the intramuscular cell infiltration and mRNA levels of the inflammatory mediators. After CALP1 treatment, a substantial up-regulation in Ca2+ /calmodulin-dependent protein kinase II (CaMKII), Ca2+ /calmodulin-dependent protein kinase IV (CaMKIV) and nuclear factor of activated T cells (NFAT) activity was detected in CD45+ cells isolated from the damaged muscle. More pro-inflammatory F4/80+ Ly-6C+ cells were detected in CD45-gated cells after CALP1 treatment than in those after CCL treatment or no treatment. Consistently, in interferon-γ-stimulated cultured myoblasts and myotubes, CALP1 treatment up-regulated the activities of CaMKII, CaMKIV and NFAT, and levels of class I/II major histocompatibility complexes (MHC-I/II) and TLR3. Our findings demonstrated that CaM-dependent signalling pathways mediate the injury-induced acute muscle inflammatory response.

Preparation of adriamycin gelatin microsphere-loaded decellularized periosteum that is cytotoxic to human osteosarcoma cells.

The purpose of this study was to develop a novel approach to treat bone osteosarcoma using a multipurpose scaffold aiming for local drug delivery. The slowly releasing microspheres was designed to deliver the chemotherapy drug adriamycin (ADM) and a decellularized (D) periosteum scaffold (which is known to be able to promote bone regeneration) was used to carry these microspheres. D-periosteum was obtained by physical and chemical decellularization. Histological results showed that the cellular components were effectively removed. The D-periosteum showed an excellent cytocompatibility and the ability to promote adhesion and growth of fibroblasts. Two kinds of slowly releasing microspheres, adriamycin gelatin microspheres (ADM-GMS) and adriamycin poly (dl-lactide-co-glycolide) gelatin microspheres (ADM-PLGA-GMS), were prepared and anchored to D-periosteum, resulting in two types of drug-releasing regenerative scaffolds. The effectiveness of these two scaffolds in killing human osteosarcoma cells was tested by evaluating cell viability overtime of the cancer cells cultured with the scaffolds. In summary, a gelatin/decellularized periosteum-based biologic scaffold material was designed aiming for local delivery of chemotherapy drugs for osteosarcoma, with the results showing ability of the scaffolds in sustaining release of the cancer drug and in suppressing growth of the cancer cells in vitro.

Aberrant expression of long noncoding RNA SNHG15 correlates with liver metastasis and poor survival in colorectal cancer.

Long noncoding RNAs (lncRNAs) play a critical role in the initiation and progression of colorectal cancer (CRC), but little is known about the function of lncRNAs in the colorectal liver metastasis (CLM). This study was designed to identify specific lncRNAs correlating to liver metastasis of CRC, and to further assess their clinical value. Seventeen patients with primary CRC lesions, adjacent normal mucosa, and synchronous liver metastases lesions were divided into discovery set (six patients) and test set (11 patients). Transcriptome sequencing (RNAseq) was used to screen differential expression of lncRNAs in the discovery set. Based on bioinformatics data, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to verify the target lncRNA in test set. The relationships between target lncRNA and clinical values were analysed in an expanded validation set of additional 91 patients. 23 upregulated and 14 downregulated lncRNAs were detected for distinguishing synchronous liver metastases, primary CRC lesions from adjacent normal mucosa in the RNAseq set. The expression levels of four lncRNAs in the 37 lncRNA signature were verified by qRT-PCR in the test set. Compared with the paired normal mucosa, high expression levels of lnc-small-nucleolar RNA host gene 15 (SNHG15) were detected not only in primary CRC lesions but also in liver metastases lesions in the test set. Furthermore, in the expanded validation set, high expression of lnc-SNHG15 was significantly associated with lymph-node metastasis and liver metastasis (p < 0.05), and patients displaying high lncRNA-SNHG15 expression exhibited a shorter median overall survival duration than those displaying low expression (30.7 vs. 35.2 months; p = 0.003). Multivariate analyses demonstrated that lncRNA-SNHG15 overexpression may serve as a poor prognostic biomarker for CRC patients (p = 0.049; Cox's regression: 2.731). Lnc-SNHG15 overexpression was significantly associated with CLM and high-expression of lnc-SNHG15 in CRC was an independent predictor of poor survival.

Associations between the cyclooxygenase-2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer.

While previous studies have shown that the number of circulating tumor cells (CTCs) alone is not sufficient to reflect tumor progression and that cyclooxygenase-2 (COX-2) expression is correlated with colorectal cancer (CRC) metastasis, COX-2 expression status and its potential functions in CTCs of CRC patients are unknown. Here, epithelial-mesenchymal transition (EMT) phenotype-based subsets of CTCs and the COX-2 expression status in CTCs were identified and their potential clinical values were assessed in 91 CRC patients. CTCs were enumerated in peripheral blood and subsets of CTCs (epithelial [eCTCs], mesenchymal [mCTCs], and biophenotypic [bCTCs]) and the COX-2 expression status were determined using the RNA in situ hybridization method. CTCs were detected in 80.2% (73 of 91) patients. Neither the total CTC nor eCTC numbers were found to significantly associate with any of the clinicopathological features. However, the number of mCTCs was significantly associated with distance metastasis (P = 0.035) and had a trend of being associated with lymph node metastasis ( P = 0.055). Among the 73 patients enrolled for evaluating COX-2 expression, 52.5% (38 of 73) were found to express COX-2 in CTCs, and COX-2 expression in CTCs was not found to associate with the clinicopathological factors. However, COX-2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%; P = 0.072). Furthermore, COX-2 expression and mCTC marker expression correlated positively ( R = 0.287; P = 0.017). Further studies are required to investigate the clinical value of the expression of COX-2 in mCTCs, especially in CRC patients with the advanced tumor stage and distant metastasis.

Computational Modeling of Bone Cells and Their Biomechanical Behaviors in Responses to Mechanical Stimuli.

Bone cells, including osteoblasts, osteoclasts, and osteocytes, have the ability to develop and maintain bone architecture. Although improved experimental testing approaches are increasing our understanding of the complex structures and functions of bone cells and bone, computational models, particularly finite element analyses, are being used to extend this knowledge and to develop a more theoretical understanding of bone cell behaviors. There are many challenges to developing an accurate and validated computational model due to the complex structure and biomechanical behaviors of the bone cells and bone tissue. A better understanding of the geometry and material properties of bone cells and bone will improve our understanding of the bone's biomechanical behaviors. In this review, we summarize and discuss the different geometric representations and material properties that have been used to model the bone cells. The current status of computational models, a comprehensive overview of the modeling methods for the bone cells, and the challenges for validating the models are presented.

An enhanced staining method K-B-2R staining for three-dimensional nerve reconstruction.

BACKGROUND: Three-dimensional (3D) reconstruction of human peripheral nerves, as a useful tool to understand the nerve internal information and functional basis, has become an important area of research in the peripheral nerve field. METHODS: In this study, we proposed a two-dimensional (2D) Karnovsky-Roots toluidine blue ponceau 2R (K-B-2R) staining method based upon conventional Karnovsky-Roots staining. It significantly improved the ability to display nerve fascicles, motor and sensory nerve fiber textures. In this method, Karnovsky-Roots staining was carried out, followed by toluidine blue counterstain and ponceau 2R counterstain. RESULTS: Comparisons were conducted between the three methods in staining of median nerve sections, which showed similar distribution characters in acetylcholinesterase-positive sites. The additional counterstaining did not change the basis of Karnovsky-Roots staining. However, the resulting images from this new method significantly facilitated the subsequent 3D nerve reconstruction and 3D printing. CONCLUSIONS: These results show that the new staining method significantly enhanced the display qualities of nerve fascicle edges and fiber textures of motor and sensory nerves and facilitated 3D nerve reconstruction.

Propeller perforator flaps from the dorsal digital artery perforator chain for repairing soft tissue defects of the finger.

BACKGROUND: When restoring the appearance and function of the fingers, hand surgeons face a challenge in choosing a suitable surgical method to repair finger skin defects. METHODS: In this study, we designed a long elliptical flap based on a propeller perforator flap and located slightly toward the dorsal lateral aspect of the finger. The flap with a pedicle consisting of the dorsal perforator of the distal digital artery and dorsal digital artery perforator chain is rotated to cover a large wound on the distal end. From December 2014 to December 2017, 10 patients with finger soft tissue defects were treated with the propeller perforator flap described in this study. RESULTS: All flaps survived after surgery, and 2 had a transient venous congestion. After a follow-up period of 3 to 12 months, the static two-point discrimination of the flap was 8.06 ± 1.75 mm, and the range of motion was 149.4 ± 12.9°. This designed flap can span several angiosomes supplied by the perforators. Due to the inclusion of a vessel chain between the dorsal digital artery perforators, the length-to-width ratio of the flap can be up to 3:1. CONCLUSIONS: This technique increases the size of flap that can be harvested safely while retaining a reliable blood supply. The present study describes a new method for repairing soft tissue defects of the finger by using the technique of propeller perforator flaps based on dorsal digital artery perforator chains. TRIAL REGISTRATION: The registration number of this study is ChiCTR1800014588; it has been retrospectively registered with Chinese Clinical Trial Registry (chictr.org.cn), 18/11/2019.

A 3D-Printed Scaffold for Repairing Bone Defects.

The treatment of bone defects has always posed challenges in the field of orthopedics. Scaffolds, as a vital component of bone tissue engineering, offer significant advantages in the research and treatment of clinical bone defects. This study aims to provide an overview of how 3D printing technology is applied in the production of bone repair scaffolds. Depending on the materials used, the 3D-printed scaffolds can be classified into two types: single-component scaffolds and composite scaffolds. We have conducted a comprehensive analysis of material composition, the characteristics of 3D printing, performance, advantages, disadvantages, and applications for each scaffold type. Furthermore, based on the current research status and progress, we offer suggestions for future research in this area. In conclusion, this review acts as a valuable reference for advancing the research in the field of bone repair scaffolds.

Advancing the Frontiers of Neuroelectrodes: A Paradigm Shift towards Enhanced Biocompatibility and Electrochemical Performance.

The aim of this study is the fabrication of unprecedented neuroelectrodes, replete with exceptional biological and electrical attributes. Commencing with the synthesis of polyethylene glycol and polyethyleneimine-modified iron oxide nanoparticles, the grafting of Dimyristoyl phosphatidylcholine was embarked upon to generate DMPC-SPION nanoparticles. Subsequently, the deposition of DMPC-SPIONs onto a nickel-chromium alloy electrode facilitated the inception of an innovative neuroelectrode-DMPC-SPION. A meticulous characterization of DMPC-SPIONs ensued, encompassing zeta potential, infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses. Evaluations pertaining to hemolysis and cytotoxicity were conducted to ascertain the biocompatibility and biosafety of DMPC-SPIONs. Ultimately, a comprehensive assessment of the biocompatibility, electrochemical properties, and electrophysiological signal acquisition capabilities of DMPC-SPION neuroelectrodes was undertaken. These findings conclusively affirm the exemplary biocompatibility, electrochemical capabilities, and outstanding capability in recording electrical signals of DMPC-SPION neuroelectrodes, with an astounding 91.4% augmentation in electrode charge and a noteworthy 13% decline in impedance, with peak potentials reaching as high as 171 µV and an impressive signal-to-noise ratio of 15.92. Intriguingly, the novel DMPC-SPION neuroelectrodes herald an innovative pathway towards injury repair as well as the diagnosis and treatment of neurological disorders.

Increasing the Particle Size and Magnetic Property of Iron Oxide Nanoparticles through a Segregated Nucleation and Growth Process.

Iron oxide nanoparticles (IONs) with good water dispersibility were prepared by the thermal decomposition of iron acetylacetonate (Fe(acac)3) in the high-boiling organic solvent polyethylene glycol (PEG) using polyethyleneimine (PEI) as a modifier. The nucleation and growth processes of the crystals were separated during the reaction process by batch additions of the reaction material, which could inhibit the nucleation but maintain the crystal growth, and products with larger particle sizes and high saturation magnetization were obtained. The method of batch addition of the reactant prepared IONs with the largest particle size and the highest saturation magnetization compared with IONs reported using PEG as the reaction solvent. The IONs prepared by this method also retained good water dispersibility. Therefore, these IONs are potentially suitable for the magnetic separation of cells, proteins, or nucleic acids when large magnetic responses are needed.

The Protective Effects of Mogroside V Against Neuronal Damages by Attenuating Mitochondrial Dysfunction via Upregulating Sirtuin3.

Mitochondrial dysfunction and oxidative stress are thought to play a dominant role in the pathogenesis of Parkinson's disease (PD). Mogroside V (MV), extracted from Siraitia grosvenorii, exhibits antioxidant-like activities. The aim of this study was to investigate the function of MV in neuroprotection in PD and to reveal its mechanism of action. To that end, we firstly set up mice models of PD with unilateral striatum injection of 0.25 mg/kg rotenone (Rot) and co-treated with 2.5 mg/kg, 5 mg/kg, and 10 mg/kg MV by gavage. Results showed that Rot-induced motor impairments and dopaminergic neuronal damage were reversed by treatment of 10 mg/kg MV. Then, we established cellular models of PD using Rot-treated SH-SY5Y cells, which were divided into six groups, including control, Rot, and co-enzyme Q10 (CQ10), as well as MV groups, MV25, MV50, and MV100 treated with 25 µM, 50 µM, and 100 µM MV doses, respectively. Results demonstrated that MV effectively attenuates Rot neurotoxicity through a ROS-related intrinsic mitochondrial pathway. MV reduced overproduction of reactive oxygen species (ROS), recovered the mitochondrial membrane potential (MMP), and increased the oxygen consumption rate and adenosine triphosphate (ATP) production in a dose-dependent manner. Hence, treatment with MV led to a reduction in the number of apoptotic cells, as reflected by Annexin-V/propidium iodide co-staining using flow cytometry and TdT-mediated dUTP Nick-End Labeling (TUNEL) assay. In addition, the Sirtuin3 (SIRT3) protein level and activity were decreased upon exposure to Rot both in substantia nigra (SN) of mice and SH-SY5Y cells. SIRT3 impairment hyperacetylated a key mitochondrial antioxidant enzyme, superoxide dismutase 2 (SOD2). MV alleviates SIRT3 and SOD2 molecular changes. However, after successfully inhibiting SIRT3 by its specific inhibitor 3-1H-1, 2, 3-triazol-4-yl pyridine (3TYP), MV was not able to reduce ROS levels, reverse abnormal MMP, or decrease apoptotic cells. Motor impairments and dopaminergic neuronal injury in the SN were alleviated with the oral administration of MV in Rot-treated PD mice, indicating a relationship between protection against defective motility and preservation of dopaminergic neurons. Therefore, we conclude that MV can alleviate Rot-induced neurotoxicity in a PD model, and that SIRT3 may be an important regulator in the protection of MV.

Neuroprotective effect of magnesium supplementation on cerebral ischemic diseases.

Ischemic encephalopathy is associated with a high mortality and rate of disability. The most common type of ischemic encephalopathy, ischemic stroke, is the second leading cause of death in the world. At present, the main treatment for ischemic stroke is to reopen blocked blood vessels. However, despite revascularization, many patients are not able to achieve good functional results. At the same time, the strict time window (<4.5 h) of thrombolytic therapy limits clinical application. Therefore, it is important to explore effective neuroprotective drugs for the treatment of ischemic stroke. Magnesium is a natural calcium antagonist, which exerts neuroprotective effects through various mechanisms. However, while most basic studies have shown that magnesium supplementation can help treat cerebral ischemia, intravenous magnesium supplementation in large clinical trials has failed to improve prognosis of ischemic patients. Therefore, we review the basic and clinical studies of magnesium supplementation for cerebral ischemia. According to the route of administration, treatment can be divided into intraperitoneal magnesium supplementation, intravenous magnesium supplementation, arterial magnesium supplementation and intracranial magnesium supplementation. We also summarized the potential influencing factors of magnesium ion intervention in cerebral ischemia injury. Finally, in combination with influencing factors derived from basic research, this article proposes three future research directions, including magnesium supplementation into the circulatory system combined with magnesium supplementation in the lateral ventricle, magnesium supplementation in the lateral ventricle combined with hypothermia therapy, and lateral ventricle magnesium supplementation combined with intracarotid magnesium supplementation combined with selective hypothermia.