Ameliorating Mitochondrial Dysfunction of Neurons by Biomimetic Targeting Nanoparticles Mediated Mitochondrial Biogenesis to Boost the Therapy of Parkinson's Disease.

Mitochondrial dysfunction of neurons is the core pathogenesis of incurable Parkinson's disease (PD). It is crucial to ameliorate the mitochondrial dysfunction of neurons for boosting the therapy of PD. Herein, the remarkable promotion of mitochondrial biogenesis to ameliorate mitochondrial dysfunction of neurons and improve the treatment of PD by using mitochondria-targeted biomimetic nanoparticles, which are Cu2- x Se-based nanoparticles functionalized with curcumin and wrapped with DSPE-PEG2000 -TPP-modified macrophage membrane (denoted as CSCCT NPs), is reported. These nanoparticles can efficiently target mitochondria of damaged neurons in an inflammatory environment, and mediate the signaling pathway of NAD+ /SIRT1/PGC-1α/PPARγ/NRF1/TFAM to alleviate 1-methyl-4-phenylpyridinium (MPP+ )-induced neuronal toxicity. They can reduce the mitochondrial reactive oxygen species, restore mitochondrial membrane potential (MMP), protect the integrity of mitochondrial respiratory chain, and ameliorate mitochondrial dysfunction via promoting mitochondrial biogenesis, which synergistically improve the motor disorders and anxiety behavior of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. This study demonstrates that targeting mitochondrial biogenesis to ameliorate mitochondrial dysfunction has a great potential in the treatment of PD and mitochondria-related diseases.

Efficacy and safety of fire needle combined with cupping for acute herpes zoster and postherpetic neuralgia: A protocol for systemic review and meta-analysis.

BACKGROUND: Herpes zoster and post-herpetic neuralgia showed an increasing incidence during past two decades. Most of herpes zoster and post-herpetic neuralgia patients suffered from pain, anxiety, and depression. Fire needle combined with cupping is becoming a popular way to relieve the pain caused by herpes zoster and decrease the incidence of post-herpetic neuralgia. In this study, we aim to investigating the efficacy and safety of fire needle combined with cupping for the treatment of acute herpes zoster and postherpetic neuralgia (PHN). METHODS: The literature search will be carried out in following databases: PubMed/MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and Wanfang Data. Published and unpublished controlled trials compared fire needle combined with cupping to other treatments for acute herpes zoster or PHN will be included. Data from eligible studies will be extracted by 2 independent reviewers. Different scales will be used to assess the risk of bias based on the study design. Pain intensity and PHN are primary outcomes. The final effect size will be reported using 95% confidence interval at 0.05 significance level. DISCUSSION: This review will provide certain evidence to compare the efficacy and safety of combined acupuncture and cupping with guideline recommended drug or nerve block therapy for the treatment of herpes zoster and post-herpetic neuralgia. It will potentially provide more clinical suggestions and guidelines for health care professionals, policymakers, and researchers.

[Effect of Angelica sinensis polysaccharide on the osteogenic differentiation of bone marrow mesenchymal stem cells of rats with high glucose levels].

OBJECTIVE: This study aims to evaluate the effect of Angelica sinensis polysaccharide (ASP) on the osteogenic differentiation of the bone marrow mesenchymal stem cells (BMSCs) of rats with high glucose levels. METHODS: Rat BMSCs were isolated and identified by osteogenic and adipogenic differentiation. Then, the BMSCs were divided into three groups as follows: normal control group (5.5 mmol·L⁻¹ glucose), high glucose group (25.5 mmol·L⁻¹ glucose), and ASP+high glucose group (25.5 mmol·L⁻¹ glucose +40 mg·L⁻¹ ASP). The proliferation activities of the BMSCs were detected by CCK8. Alizarin red staining, and alkaline phosphatase activity were used in the examination of osteogenic activity. Quantitative real time-polymerase chain reaction was used to detect the expression levels of the osteogenic genes (Runx2, Osx, OCN, Col-Ⅰ) and the key factors of Wnt/ß-catenin signal pathway (CyclinD1, ß-catenin). In vivo, a type 2 diabetes rat model was established. The rats were divided into three groups, namely, the normal control group (normal rats), diabetes group (diabetic rats), diabetes+ASP group (diabetic rats, ASP feeding). Then, the tibia bone defect was established. The repair of bone defects in each group was observed through histological examination. RESULTS: The proliferation of BMSCs was higher in the high glucose group and ASP+high glucose group than in the normal control group (P<0.05). No significant difference was observed between the high glucose group and ASP+high glucose group (P>0.05). The number of calcium nodules of BMSCs; alkaline phosphatase activity; and the mRNA expression of Runx2, OCN, Osx, Col-Ⅰ, CyclinD1, ß-catenin in the high glucose group were lower than those in the normal control and ASP+high glucose groups (P<0.05). No significant difference was observed between the normal control and ASP+high glucose groups (P>0.05). The bone mass was significantly lower in the bone defect of the diabetes group than in the bone defect of the normal control or diabetes+ASP group (P<0.05). No statistical difference was found between the normal control and diabetes+ASP groups (P>0.05). CONCLUSIONS: ASP can promote the osteogenic differentiation of rat BMSCs under high glucose culture and induce bone regeneration in rats with type 2 diabetes. These features may be related to the activation of the Wnt/ß-catenin signaling pathway.

Cholesterol-Modified Black Phosphorus Nanospheres for the First NIR-II Fluorescence Bioimaging.

Black phosphorus (BP) nanostructures with unique layer-dependent properties have been extensively applied in the fields of electronic devices, energy conversion and storage, and nanomedicine. As a narrow band gap semiconductor, they are expected to show strong second near-infrared (NIR-II) fluorescence. However, there is no report on the NIR-II fluorescence of free-standing BP nanostructures, which have great potential in the NIR-II fluorescence bioimaging because of their excellent biocompatibility and biodegradability. Here, for the first time, we report that the BP nanoparticles modified with cholesterol exhibit strong NIR-II fluorescence and can be encapsulated with the PEGylated lipid to form BP@lipid-PEG nanospheres for in vitro and in vivo NIR-II imaging. The resultant BP@lipid-PEG nanospheres exhibit broad emissions from 900 to 1650 nm under excitation by an 808 nm laser and have 8% quantum yield of that of standard dye IR-26. We also show that the NIR-II fluorescence image acquired with emission beyond 1400 nm has the sharpest contrast and can be used to in situ measure the diameter of blood vessels. In addition to NIR-II fluorescence imaging, we also show the potential of BP@lipid-PEG nanospheres in photoacoustic (PA) imaging. Both the long-wavelength NIR-II fluorescence imaging and PA imaging reveal that the as-fabricated BP@lipid-PEG nanospheres can be gradually metabolized by the liver in 48 h, thus making them promising for bioapplications.

Second near-infrared photodynamic therapy and chemotherapy of orthotopic malignant glioblastoma with ultra-small Cu2-xSe nanoparticles.

The treatment of malignant glioblastoma is a huge challenge due to the existence of the blood-brain barrier. Herein, we report the treatment of orthotopic malignant glioblastoma with imaging guided second near-infrared (NIR-II) photodynamic therapy and chemotherapy by using drug-loaded ultra-small Cu2-xSe theranostic nanoparticles (NPs). Ultra-small Cu2-xSe NPs possess a strong absorbance in the NIR-II window, and their absorption at 1064 nm is around 2 times that at 808 nm. Their strong NIR-II absorbance and the deeper-tissue penetration of NIR-II light ensure excellent photodynamic therapy performance under irradiation with a 1064 nm laser. We also demonstrate that ultra-small Cu2-xSe NPs can produce vast amounts of reactive oxygen species via electron transfer (for ˙OH generation) and energy transfer (for 1O2 generation) mechanisms under irradiation. In addition, these NPs can be effectively and locally transported into orthotopic malignant glioblastoma with the assistance of focused ultrasound. The deposited Cu2-xSe NPs can be used for photoacoustic imaging to guide the combined NIR-II photodynamic therapy and chemotherapy. The results show that the tumor growth can be significantly suppressed. This work demonstrates the great potential of drug-loaded ultra-small Cu2-xSe NPs as a promising therapeutic agent for the treatment of orthotopic malignant glioblastoma.

Boosting the Radiosensitizing and Photothermal Performance of Cu2- xSe Nanocrystals for Synergetic Radiophotothermal Therapy of Orthotopic Breast Cancer.

The small difference between tumor and normal tissues in their responses to ionizing radiation has been a significant issue for radiotherapy of tumors. Herein, we report that dumbbell-shaped heterogeneous copper selenide-gold nanocrystals can serve as an efficient radiosensitizer for enhanced radiotherapy. The mean lethal dose of X-rays to 4T1 tumor cells can be drastically decreased about 40%, that is, decreasing from 1.81 to 1.10 Gy after culture with heterostructures. Due to the synergetic effect of heterostructures, the dose of X-rays is also much lower than those obtained from mixture of Cu2- xSe + Au nanoparticles (1.78 Gy), Cu2- xSe nanoparticles (1.72 Gy) and Au nanoparticles (1.50 Gy), respectively. We demonstrate that the sensitivity enhancement ratio of Cu2- xSe nanoparticles was significantly improved 45% ( i. e., from 1.1 to 1.6) after the formation of heterostructures with gold. We also show that the heteronanocrystals exhibit an enhanced photothermal conversion efficiency, due to the synergetic interactions of localized surface plasmon resonance. These properties highly feature them as a multimodal imaging contrast agent (particularly for photoacoustic imaging, computed tomography imaging, and single photon emission computed tomography after labeled with radioisotopes) and as a radiosensitizer for imaging guided synergetic radiophotothermal treatment of cancer. The research provides insights for engineering low- Z nanomaterials with high- Z elements to form heteronanostructures with enhanced synergetic performance for tumor theranostics.

Cu-Fe-Se Ternary Nanosheet-Based Drug Delivery Carrier for Multimodal Imaging and Combined Chemo/Photothermal Therapy of Cancer.

Ternary transition-metal chalcogenide nanosheets have shown great potential in diverse applications owing to their intrinsically amazing properties with a broad tunable window. Direct preparation of water-soluble and biocompatible ternary chalcogenide nanosheets for theranostic application remains a challenge. In this article, we prepared Cu-Fe-Se nanosheets (CFS NSs) in an aqueous solution under ambient conditions by a sequential coprecipitation method. They were functionalized with anticancer drug doxorubin (CFS@DOX) through electrostatic interactions and labeled with radioactive isotope 99mTc through surface coordination effect. The resulting nanosheets have a size of 70 nm and a thickness of 5 nm, and can be well dispersed in water, phosphate-buffered saline, 10% fetal bovine serum, and 0.9% NaCl with an excellent colloidal stability. They also exhibit a high photothermal conversion efficiency of 78.9% for in vitro and in vivo photoacoustic imaging and photothermal therapy. The isotope-labeled nanosheets (99mTc-CFS NSs) were used for single photon emission computed tomography/computed tomography imaging to quantify their blood circulation time (∼4.7 h) and biodistributions in major organs, which follow an order of liver > bladder > lung > spleen > heart > kidney. The DOX-functionalized nanosheets (CFS@DOX) were used for chemotherapy of cancer and exhibited excellent anticancer efficacy. Our research shows the great promise of ternary metal chalcogenide nanosheets for combined imaging and therapy of cancer.

Evaluation of Three Block Anesthesia Methods for Pain Management During Mandibular Third Molar Extraction: A Meta-analysis.

A patient's pain during mandibular third molar extraction often creates problems for a dental surgeon and can also cause immense patient discomfort, such as decreased quality of life, serious complications, or even danger to the patients' lives. Effective pain management is therefore of great importance. Conventional block anesthesia method often fails to control such pain completely during an operation. Therefore, two available alternatives, Gow-Gates (G-G) and Vazirani-Akinosi (V-A) methods, have been developed. However, the results of current studies regarding their effectiveness and safety are somewhat ambiguous. The use of G-G and V-A techniques is therefore restricted. This study did a comprehensive review of the relevant research and finally 7 RCTs were included. The results of this meta-analysis indicate that both G-G and V-A techniques have a lower risk of positive aspiration. G-G technique also evidenced a higher success rate than the conventional method. V-A was faster while the G-G technique in contrast had a slower onset time than the conventional technique. In terms of the measurement of analgesic success, however, the V-A method was statistically indistinguishable from conventional techniques. These findings will hopefully endow clinicians with the knowledge required to make appropriate choices for effective anesthesia during lower third molar extraction.