Nanopolyphenol rejuvenates microglial surveillance of multiple misfolded proteins through metabolic reprogramming

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Establishment of an in vitro model of alveolar macrophage cell efferocytosis dysfunction / 中华危重病急救医学

Objective:To screen the time points of high survival rate and efferocytosis dysfunction of rat alveolar macrophages stimulated by cigarette smoke extract (CSE), establish an in vitro model of alveolar macrophage efferocytosis function, and study chronic respiratory diseases with chronic inflammatory reaction as the main pathological changes. Methods:① Time point screening experiment: rat alveolar macrophages (NR8383 cells) were cultured in vitro, and the cells in logarithmic growth phase were divided into blank control group (100 μL complete medium) and 5% CSE group (90 μL complete medium + 10 μL 100% CSE). Alma blue method was used to detect the effect of 5% CSE on the activity of NR8383 cells at 6, 12, 24 and 48 hours. ② Apoptosis induction experiment: rat type Ⅱ alveolar epithelial cells (RLE-6TN cells) were cultured in vitro as phagocytic target cells of NR8383 cells, and the cells in logarithmic growth phase were divided into blank control group and 10, 30 and 60 minutes groups after ultraviolet exposure (apoptosis was induced by 30 000 μJ/cm 2 ultraviolet irradiation for 15 minutes). Flow cytometry was used to detect the apoptosis rate of RLE-6TN cells cultured for 10, 30 and 60 minutes after ultraviolet exposure. ③ Cell efferocytosis experiment: NR8383 cells in logarithmic phase were divided into blank control group and 5% CSE group. Two hours before NR8383 cells were stimulated by CSE for 6, 12 and 24 hours, RLE-6TN cells were exposed to ultraviolet to induce apoptosis, and the RLE-6TN cell suspension was added to NR8383 cells (the ratio of RLE-6TN cells to NR8383 cells was 5∶1). Flow cytometry was used to detect the efferocytosis rate of NR8383 cells to RLE-6TN cells at different time points treated with 5% CSE. Results:① Compared with the blank control group, the activity of NR8383 cells significantly decreased after treatment with 5% CSE for 48 hours [cell reduction rate: (68.5±4.1)% vs. (73.6±2.3)%, P < 0.05]. However, there were no significant differences when the activities of NR8383 cells treated with 5% CSE for 6, 12 and 24 hours were compared with the blank control group, so these three time points were selected for the subsequent establishment of alveolar macrophage cell efferocytosis dysfunction in vitro model experiment. ② Compared with the blank control group, the apoptosis rate of RLE-6TN cells significantly increased at 10, 30 and 60 minutes after ultraviolet exposure [(66.87±8.63)%, (85.51±2.39)%, (96.13±2.74)% vs. (9.13±3.17)%, all P < 0.01] in a time-dependent manner. Considering that it taked about 50 minutes for RLE-6TN cells to be labeled with PKH26 membrane labeling probe, 10 minutes after ultraviolet exposure was selected to label RLE-6TN cells. ③ Compared with the blank control group, the efferocytosis function of NR8383 cells was significantly decreased after treatment with 5% CSE for 12 hours [cell efferocytosis rate: (33.64±1.30)% vs. (44.02±2.71)%, P < 0.01], but there was no significant effect on the efferocytosis function of NR8383 cells at 6 hours and 24 hours. Conclusions:CSE can induce alveolar macrophage cell efferocytosis dysfunction. Based on the test results of the effect of 5% CSE on NR8383 cell activity and cell efferocytosis function, 12 hours with high survival rate and weak efferocytosis effect of NR8383 cells can be selected as the in vitro model condition of alveolar macrophage cell efferocytosis dysfunction.

TREM-2 and tumors / 国际肿瘤学杂志

Triggering receptors expressed on myeloid cells-2 (TREM-2) is a newly discovered immunoglobulin receptor, which plays an important role in inflammation and immunoreaction. Several recent studies have shown that TREM-2 is aberrantly expressed in various types of cancers such as lung cancer, gastric cancer, liver cancer, colorectal cancer, renal carcinoma and glioma, and it is widely participated in regulating malignant tumor initiation, progression, invasion and metastasis through different signal pathways. TREM-2 is expected to provide evidence for the diagnosis and treatment of malignant tumors.

Advances in research on the role of alveolar macrophage burial function in chronic obstructive pulmonary disease / 中华危重病急救医学

As one of the top three causes of death in the world, chronic obstructive pulmonary disease (COPD) is a serious hazard to human health. Macrophages play an important role in COPD, and their efferocytosis function is essential for ending chronic inflammation of COPD. Efferocytosis damage of alveolar macrophages (AM) in patients with COPD causes the rising of bacterial infection and airway bacterial colonization risk in lungs, which is the main reason for the acute exacerbation and the rising of incidence rate and mortality rate in COPD. In recent years, the regulation of macrophage efferocytosis function in COPD has becoming a research hotspot. Progress on the role of macrophage efferocytosis function on COPD, and the breakthrough points of improving AM efferocytosis dysfunction by traditional Chinese medicine is reviewed, so as to provide new ideas for the prevention and treatment of COPD.

ThevalueofthefusiontechnologyofbronchialarteryCTAwith 3Dreconstructionoftracheaininterventionaltreatmentsforhemoptysis / 实用放射学杂志

Objective TodiscussthevalueofthefusiontechnologyofbronchialarteryCTA with3Dreconstructionoftracheain interventionaltreatmentsforhemoptysis.Methods AretrospectiveanalysiswasconductedinthefusionimagesofthebronchialarteryCTA with 3DreconstructionoftracheaandDSAin58patientswithhemoptysis,therelatedparametersofthebronchialartery(BA)wereobserved (the typeofBA,thebronchialopening,thebronchialoriginandthepositionrelationshipbetweenthebronchus),andthestatisticalanalysiswas performed.Results Inthe58hemoptysispatients,CTArevealed156BAs,including73leftBAs,76rightBAsand7heterotopic BAs.Therewere67BAsresponsibleforhemoptysis,ofwhich64BAswerefromnormaloriginand3BAswerefromheterotopicorigin.Four typesofBAswerefoundandthemostwereR1L1,accountingfor44.8%.BAsaboveandbelowthetrachealcarinaaccountedfor61.5% and 38.5%,respectively.Themeandiameterwas(3.56±1.21)mmforBAsresponsibleforhemoptysisand (1.67±0.32)mmforBAs irresponsibleforhemoptysis.Conclusion ThefusiontechniqueofbronchialarteryCTAandtracheal3Dreconstructionoftracheacan welldetecttheoriginofthesuspectedhemoptysisresponsibilityBA,theposition,andtherelationshipbetweentheshapeandthebifurcation ofthebronchusI.tcanbeusedasthefirstchoiceofroutineexaminationforhemoptysisinterventionaltherapy.

Evaluation of the super-selective prostate artery embolization combined with TURP for patients with large volume (＞ 80 ml) benign prostatic hyperplasia / 中华泌尿外科杂志

Objective To explore the saffety and efficacy of super-selective prostate artery embolization (PAE) combined with TURP (transurethral resection of prostate) as an alternative method for patients with severe large BPH (＞ 80 ml).Methods From March 2015 to June 2017,a total of 40 patients with large benign prostatic hyperplasia who failed in medical treatment were selected for PAE combined with TURP (18 cases)and TURP (22 cases).In the PAE combined with TURP group,the mean age was (75.0±8.7) years (ranging60-88 years) and the mean prostatic volume was (111.0 ±23.3) ml,ranged from 83 to 145 ml).The international prostate symptom score (IPSS),quality of life (QOL),maximal t rine flow rate (Qmax) and postvoid residual urine(PVR) were(25.2 ±3.6),(5.1 ± 1.0),(6.4 ± 2.3) ml/s and (107.7 ± 32.6) ml,respectively.In the TURP group,the mean age was (76.0 ± 6.9) years (ranging 62-85 years) and the mean prostatic volume was (107.5 ±27.4) ml,ranged from 80 to 150 ml).The IPSS,QOL,Q andPVRwere(24.3±4.2),(4.9 ±0.9),(6.7±2.2)ml/s and (106.6±32.2)ml,respectively.Clinical data of all of patients were analyzed retrospectively,including operative time,estimate blood loss,weight and efficacy of resected tissue,time of continuous bladder irrigation and catheterization,IPSS,QOL,PVR,Q and postoperative complications.Results There were significant differences in the operative time [(75.8 ± 25.1) min vs.(103.2 ± 27.7) min],estimate blood loss [(122.8 ± 33.9) ml vs.(447.6 ± 36.0) ml],weight of resected tissue [(99.9 ± 24.2) g vs.(82.9 ± 15.5) g],efficacy of resected tissue [(76.9 ± 20.7) g/h vs.(41.7 ± 14.2) g/h],continuous bladder irrigation time [(1.4 ± 0.5) d vs.(2.4 ± 0.8) d] and catheterization time [(2.2 ± 0.4) d vs.(3.4 ± 0.6) d] between PAE combined TURP group and TURP group (P ＜ 0.05).The postoperative complications of PAE combined TURP group and TURP group were included secondary hemorrhage (0 case vs.3 cases),secondary TURP (0 case vs.3 cases),temporary urinary incontinence (2 case vs.4 case),urinary tract infection (1 case vs.2 case).After 1-year follow up,the IPSS,QOL,Qmax and PVR of PAE combined TURP group and TURP group were (6.7 ±1.5)and(6.9± 1.5),(2.3 ±0.5) and(2.3 ±0.6),(15.6 ±2.3) ml/s and(15.0 ±2.1) ml/s,(32.8±6.5) ml and(32.3± 8.4)ml,respectively.Both goups were found to have significantly improved in IPSS,QOL,Q and PVR,as compared with preoperative indexes,respectively (P ＜ 0.05).However,there was no significant difference in those indexes between two groups (P ＞ O.05).Conclusions PAE combined TURP could be used a safe and effective therapy for treating patients with LUTS due to large volume (＞ 80 ml) BPH.It has been a priority in less blood,more efficient of resected tissue and less postoperative complications.

Leukocyte-derived biomimetic nanoparticulate drug delivery systems for cancer therapy

Precise drug delivery to tumors with low system toxicity is one of the most important and challenging tasks for pharmaceutical researchers. Despite progress in the field of nanotherapeutics, the use of artificially synthesized nanocarriers still faces several challenges, including rapid clearance from blood circulation and limited capability of overcoming multiple physiological barriers, which hamper the clinical application of nanoparticle-based therapies. Since leukocytes (including monocytes/macrophages, neutrophils, dendritic cells and lymphocytes) target tumors and can migrate across physiological barriers, leukocytes are increasing utilized as carriers to transfer nanoparticles to tumors. In this review we specifically focus on the molecular and cellular mechanisms of leukocytes that can be exploited as a vehicle to deliver nanoparticles to tumors and summarize the latest research on how leukocytes can be harnessed to improve therapeutic end-points. We also discuss the challenges and opportunities of this leukocyte-derived nanoparticle drug delivery system.

Reconstituted high-density lipoproteins: novel biomimetic nanocarriers for drug delivery

High-density lipoproteins (HDL) are naturally-occurring nanoparticles that are biocompatible, non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and microRNA from donor cells to recipient cells. Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins (rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative, promising avenue for efficient targeting transport of nanomedicine.

Electrochemical Determination of Bisphenol A on a Glassy Carbon Electrode Modified with Gold Nanoparticles Loaded on ReducedGraphene Oxide-Multi-Walled Carbon Nanotubes Composite / 分析化学

A glassy carbon electrode (GCE) modified with gold nanoparticles loading on the reduced graphene oxide (rGO)-multi-walled carbon nanotubes (MWCNTs) composite film was fabricated by a two-step procedure.Firstly, rGO-MWCNTs composite were prepared by in-situ chemical reduction method with hydrazine as a reducing agent.Then, AuNPs were deposited on the surface of rGO-MWCNTs using simple cyclic voltammetry.This modified electrode was characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS) and electrochemical methods.Furthermore, the electrochemical behavior of bisphenol A (BPA) was also investigated using this modified electrode.The results showed that the modified electrode had high electrochemical activity for the oxidation of BPA.In 0.10 mol/L phosphate buffer solution (PBS, pH 7.0), the linear range for the determination of BPA with differential pulse voltammetry (DPV) was in the range of 5.0 × 10-9 -1.0 × 10-7 mol/L and 1.0 × 10-7-2.0 × 10-5 mol/L.The detection limit was 1.0 × 10-9 mol/L (S/N=3).The as-prepared modified electrode was successfully used to determine BPA in river water and the shopping receipt samples with recovery ranges of 97%-110% and 98%-104%, respectively.

Pevalence rate of healthcare-associated infection in a maternal and child health care hospital / 中国感染控制杂志

Objective To understand healthcare-associated infection(HAI)in a maternal and child health care hos-pital,so as to provide scientific evidences for further targeted surveillance.Methods A cross-sectional survey was performed by bedside visiting and medical record reviewing.Results Of 768 hospitalized patients,9(1 .18%)had HAI,the top 3 highest prevalence rates were found in obstetrical intensive care unit (9.09%),neonatal intensive care unit (5.80%)and gynecological department II(2.22%).Antimicrobial usage rate was 30.34%(n=233),134 of which (57.51 %)were prophylactic use,165 were mono-therapy(70.82%).A total of 5 pathogenic bacteria were isolated,the number of Streptococcus agalactiae ,Klebsiella pneumonia ,Enterococcus faecalis ,and Staphylococcus saprophyticus was 2,1 ,1 ,and 1 respectively,except Streptococcus agalactiae ,the other 3 strains were multidrug-resistant organisms(MDROs).Conclusion Surveillance on MDRO infection should be paid much attention,the oc-currence of MDRO infection should be reduced through targeted and bundle intervention.

Effects of antidepressant agents on the neuropathic pain induced by oxaliplatin / 中国癌症杂志

Background and purpose:Oxaliplatin is a new cytotoxic platinum compound widely used in antineoplastic treatments.Peripheral neuropathy characterized by allodynia remains the most common way to limit the usage of oxaliplatin.Oxaliplatin-associated neuropathic pain is often resistant to standard analgesics.The effects of antidepressant agents such as desipramine and fluoxetine on chemotherapy-induced neuropathic pain were investigated so as to provide experimental evidence for clinical treatment.Methods:A single injection of oxaliplatin(30 mg/kg)intraperitoneal was injected into a test subject,a mouse that had chronic neuropathic pain.Using the von Frey filament as a touch stimulator,the mechanical withdrawal threshold(MWT)was measured when observing allodynia.The MWT was measured before and 1 h after the administration of desipramin and fluoxetine.Results:Desipramine and fluoxetine both have the potential to increase the MWT in mice with oxaliplatin-induced neuropathic pain.Pretreatment with antagonists such as an opioid receptor like naloxone could deepen their effects.Furthermore,when desipramine is combined with an opioid analgesic as buprenorphine,it causes an augmentation in the MWT.Conclusion:Antidepressants desipramine and fluoxetine antagonize oxaliplatin-induced neuropathic pain by inhibiting allodynia.Furthermore,the tricyclic antidepressing agent desipramine could enhance the effects of buprenorphine in subjects with oxaliplatin-induced pain,suggesting a synergistic effect for opioid analgesic.

Preparation and in vitro targeting of follicle stimulating hormone polypeptide modified nanoparticles / 中华妇产科杂志

Objective To prepare follicle stimulating hormone (FSH) polypeptide modified nanoparticles (NP) in order to achieve specific ovarian tumor targeting. Methods Expression of FSH receptor protein in human liver cancer and ovarian cancer cell lines BEL-7402, SKOV-3 and Caov-3 was detected by immunocytochemistry. The polypeptide fragment of FSH β 81 -95 amino acids (FSHL81-95)was synthesized and covalently coupled to NP. The specific binding of FSHL81-95 and FSHL81-95-NP was examined by fluorescence microscopy and flow cytometry. Results BEL-7402 and SKOV-3 cells were negative for FSH receptor staining, while Caov-3 celia were positive. The diameters of NP were about 100 nm, with a Zeta potential of -25 mV or so. Caov-3 cells showed a more specific interaction with FSHL81-95-NP than SKOV-3 cells (4. 17 ± 0. 86 and 2. 30 ± 0. 21 ; P < 0. 05). The uptake of FSHL81-95-NP was more than NP in Caov-3 cells (4. 17 ± 0. 86 and 0. 41 ± 0. 32 ; P < 0. 05 ). FSHL81-95-NP showed a selective targeting at Caov-3 cells compared with control NP. Conclusion FSH polypeptide modified NP could selectively target ovarian cancer cells expressing FSH receptor, which might contribute to specific endocytosis mediated by FSH receptor.

Study of Promoting the Hospital Science Development by Balanced Board / 中华医学教育探索杂志

Objective:By means of balanced board,we can comprehensively assess the hospital and promote the hospital science progress from four aspects such as patient,finance,interior procedure,and the study and development.Method: Introducing the source content and character of the balanced board;Introducing the reason,qualification,instruction and effect for ChongQing NO 9 Hospital to apply the balance board.Result: We assessed the balance board from finance,interior procedure,patient,study and development: The hospital's operation income structure was more reasonable;the hospital's income is equal to the economic development;the medical staff's quality had been improved;the civilization and brand of hospital were generally promoted.Conclusion:Balance board can be used in the medical treatment and health care reformation.As a management method of hospital it can be combined with the hospital assessment items.When the hospital employs the balanced board,we can combine the management object and management cost,the development of hospital and patients' satisfaction,hospital income and local economical level as well as fee for medical treatment,performance and quality in order to promote the development of hospital.

Relation of genetic polymorphism of NQO1 and GSTT1 with risks of chronic benzene poisoning / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the relation between genetic polymorphisms of NQO1, GSTT1 and risks of chronic benzene poisoning (BP).</p><p><b>METHODS</b>A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction (PCR), denaturing high-performance liquid chromatography(DHPLC) and sequencing were used to detect the single nucleotide polymorphisms(SNPs) of the promoter and complete coding-region of NQO1 gene. Multiple PCR was used to detect GSTT1 genotype.</p><p><b>RESULTS</b>In smoking population, there was 7.73-fold (95% CI: 1.71-34.97, P = 0.010) of risk in BP subjects carrying NQO1c. 609 T/T genotype, compared with those carrying C/C and C/T. genotype. In drinking population, the individuals carrying the 6th extron of NQO1c. 609 T/T homozygote genotype had a 11.00-fold(95% CI: 1.89-63.83, P = 0.005) risk of BP compared to those with NQO1c. 609 C/T and C/C genotypes.</p><p><b>CONCLUSION</b>The subjects carrying NQO1c. 609 T/T genotype and together with the habit of smoking or drinking may be more susceptible to BP.</p>

Induction of dihydroartemisinin on prostate cancer PC-3 apoptosis and its mechanism / 中草药

Objective To study the induction of dihydroartemisinin(DHA) on prostate cancer PC-3 apoptosis and its possible mechansim.Methods MTT was employed for cellular viability measurement,flow cytometry(FCM) and transmission electron microscopy(TEM) for observation of apoptosis,and immunocytochemical staining(SP) for analyzing the expression of Bcl-2 and Bax proteins in PC-3 cells treated with DHA of different concentration.Results DHA Significantly inhibited the proliferation of PC-3 cells,induced their apotosis in a time-concentration dependent manner,and led to mitochondrial swelling,nuclear fragmentations and apoptosis body formation,down-expression of Bcl-2 protein,and over-expression of Bax protein correspondence with DHA concentration.Conclusion DHA could induce the apoptosis in PC-3 cells by up-regulating Bax protein and down-regulating Bcl-2 protein.

Antagonistic effect of bilirulin on acute lung injury induced by LPS in rats / 中国病理生理杂志

AIM: To investigate the effect of bilirub in on acute lung injury (ALI) and the mechanism. METHODS: 30 male Wistar rats were divided into normal group, ALI group and bilirubin treatment group. Lung specimens were examined by histopatho logical te chnique. Lung index (LI) and lung permeability index (LPI) were measured. Moreov er, white blood cell (WBC) count, neutrophil percentage (PMN%) and the content o f protein (Pr) in the bronchoalveolar lavage fluid (BALF), as well as the conten ts of sup eroxide dismutase (SOD), malonaldehyde (MDA) and glutathione peroxidase (GSH-Px) in the lung homogenate were determined. RESULTS: (1) In ALI group: LI, WBC count, PMN%, Pr and LPI incre ased significantly compared with normal group (P 0.05) was observed. (2) In ALI group, the content of MDA was significantly high er (P0.05). CONCLUSION: Bilirubin relieves ALI induced by LPS in rats via an tioxidation.