Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy.

BACKGROUND: Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). RESULTS: In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4ß1 and αLß2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. CONCLUSION: This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.

Bioaccumulation of Cadmium Affects Development, Mating Behavior, and Fecundity in the Asian Corn Borer, Ostrinia furnacalis.

Heavy metal pollution is becoming an increasingly serious problem in agricultural ecosystems. Heavy metals such as cadmium (Cd) accumulate in the food chain and may lead to detrimental effects on the physiological functions of living organisms, including herbivorous insects. One such example is the Asian Corn Borer, Ostrinia furnacalis (Lepidoptera: Pyralidae). However, how Cd can affect the development and reproduction of O. furnacalis is largely unknown. In this study, we exposed larvae of O. furnacalis to a diet containing Cd and investigated the effects of Cd on the development, mating behavior, and fecundity of the insect. We showed that Cd accumulates in the larvae and inhibits development by extending larval and pupal duration and decreasing the survival rate. The excretion of Cd through multiple routes during the larval and pupal stages resulted in low levels of residual Cd in the adult insects, which were not fed with Cd. However, the mating behavior and fecundity of these insects were significantly affected, compared to control insects. This suggests that the bioaccumulation of heavy metals such as Cd has long lasting and detrimental effects on O. furnacalis over the entire life cycle, affecting fecundity, even when specimens are only exposed at an early life stage.

[Pollution Characteristics and Occupational Exposure Risk of Heavy Metals in Indoor and Outdoor Ambient Particles at a Scaled Electronic Waste Dismantling Plant, Northwest China].

Atmospheric particle samples (PM1.0、PM2.5、PM10) were collected from three sampling sites (indoor and outdoor workplaces of a formal e-waste dismantling plant, and upwind area) in an arid area of Northwest China. The contents of six heavy metals (Cd, Cr, Cu, Ni, Pb, and Zn) were analyzed using ICP-OES. Based on this data, the concentration levels, size distribution characteristics, and occupational exposure risks of heavy metals at the indoor and outdoor dismantling workplaces were studied. Particle analysis showed that Zn (4890 ng·m-3 indoors, 1245 ng·m-3 outdoors)、Pb (indoors 1201 ng·m-3, outdoors 240 ng·m-3), and Cu (indoors 1200 ng·m-3, outdoors 110 ng·m-3) showed higher pollution levels indoors and outdoors at the dismantling workplace. Moreover, the indoor concentration was much higher than that outdoors, indicating that the dismantling activity was the main cause of the high levels of heavy metal contamination. The indoor and outdoor air pollution characteristics were closely related to the types of electronic waste dismantled. Occupational exposure risk assessments showed that the total non-carcinogenic hazard quotient (HQ) of the indoor and outdoor dismantling workshops was 1.62×10-3, and 3.60×10-4, respectively, and the carcinogenic risk values were 2.69×10-7 and 2.59×10-9. Cd caused the greatest carcinogenic and non-carcinogenic risks at both indoor and outdoor dismantling workplaces, but it was still far below the limits (1.0) and acceptable ranges (1×10-6) stipulated by U.S. EPA, indicating that the health risks caused by heavy metals were minor or negligible. Heavy metals in the ambient particulate matter released from an adequately equipped and formally managed e-waste dismantling plant would not lead to any public health risk. The sedimentation characteristics of particulate heavy metals in different organs of the human respiratory system exhibited that the smaller the particle size was, the greater the proportion of deposition in the depths of the respiratory system was. Enterprises should make scientific and effective decisions on the respiratory health risks caused by such fine particles to the health of professional workers.

Association between body mass index and health-related quality of life among Chinese elderly-evidence from a community-based study.

BACKGROUND: This study aimed to explore the effects of (body mass index) BMI on health related quality of life (HRQoL) among the elderly in Jiangsu, China. METHODS: A total of 10,257 community dwelling elderly (≥60 years old) were enrolled in a cross-sectional study. HRQoL was measured via the Eq-5d-3 L. Chi-square tests and one-way ANOVA analyses were used to compare the frequencies and scores of Eq-5d responses among different BMI groups (defined as "underweight", "normal weight", "overweight" and "obese"). Logistic regression analyses were conducted to examine the associations between BMI and HRQoL. RESULTS: Among the subjects, the proportion of "normal weight", "underweight", "overweight" and "obese" were 66.0, 8.3, 23.1, and 2.6%, respectively. The score of the Eq-5d index among total participants was 0.8036 and the Visual Analog Scale (VAS) score was 75.47. For both the responses frequency and scores of Eq-5d-3 L, there were significant differences among BMI groups (P < 0.001). The Logistic regression model showed that both in men and women, underweight elderly were more likely to suffer low HRQoL. The adjusted odds ratio (OR) with a 95% confidence interval (CI) for Eq-5d index/VAS was 2.03 (1.48, 2.79)/1.83 (1.34, 2.50) in men and 1.47(1.09,1.98)/1.52(1.20,1.91) in women. Overweight women more likely to have a low Eq-5d index, while overweight men were less likely to have a low Eq-5d VAS. CONCLUSION: This study shows that underweight is an explicit risk factor of low HRQoL in both the male and female elderly, while the effect of overweight on low HRQoL varies slightly by gender.

[Retracted] Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

Following the publication of this article, the authors find that they are not able to reproduce the results presented in this paper. Consequently, the authors have decided to retract this paper from publication. All of the authors agree to this retraction. The authors sincerely regret this decision, and apologize to the Editor and to the readership of the Journal for any inconvenience caused. [the original article was published in Oncology Reports 33: 783-791, 2015; DOI: 10.3892/or.2014.3644].

Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis.

Acupuncture at Shuigou (GV26) shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26 (15 Hz and 1 mA, continuous wave [biphasic pulses], for 5 minutes). Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score. These findings confirm that electroacupuncture at GV26 promotes establishment of collateral circulation and angiogenesis, and improves neurological function.

ZnO-Based Nanoplatforms for Labeling and Treatment of Mouse Tumors without Detectable Toxic Side Effects.

ZnO quantum dots (QDs) were synthesized with polymer shells, coordinated with Gd(3+) ions and adsorbed doxorubicin (DOX) together to form a new kind of multifunctional ZnO-Gd-DOX nanoplatform. Such pH sensitive nanoplatforms were shown to release DOX to cancer cells in vitro and to mouse tumors in vivo, and reveal better specificity and lower toxicity than free DOX, and even better therapeutic efficacy than an FDA approved commercial DOX-loading drug DOX-Liposome Injection (DOXIL, NDA#050718). The ZnO-Gd-DOX nanoplatforms exhibited strong red fluorescence, which benefited the fluorescent imaging on live mice. Due to the special structure of ZnO-Gd-DOX nanoparticles, such nanoplatforms possessed a high longitudinal relaxivity r1 of 52.5 mM(-1) s(-1) at 0.55 T, which was superior to many other Gd(3+) based nanoparticles. Thus, both fluorescence labeling and magnetic resonance imaging could be applied simultaneously on the tumor bearing mice along with drug delivery. After 36 days of treatment on these mice, ZnO-Gd-DOX nanoparticles greatly inhibited the tumor growth without causing any appreciable abnormality in major organs. The most important merit of ZnO-Gd-DOX was that such a nanoplatform was biodegraded completely and showed no toxic side effects after H&E (hematoxylin and eosin) staining of tumor slices and ICP-AES (inductively coupled plasma atomic emission spectrometry) bioanalyses.

Efficacy of dual-functional liposomes containing paclitaxel for treatment of lung cancer.

This study was mainly focused on the development of a dual-ligand liposomal delivery system for targeting the delivery of paclitaxel (PTX) to lung cancer. The specific ligand peptide HAIYPRH (T7) and the cationic cell-penetrating peptide TAT were connected with phospholipid via a polyethylene glycol (PEG) spacer to prepare the dual-ligand liposomes (T7/TAT-LP-PTX). Physicochemical characterizations of T7/TAT-LP-PTX, such as particle size, ζ potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. In the cellular uptake study, the T7/TAT-LP endocytosed by the A549 cells was 2.26-, 3.48- and 8.56-fold higher than TAT-LP, T7-LP and LP, respectively. The IC50 values of TAT-LP-PTX, T7-LP-PTX and LP-PTX were much higher than those of T7/TAT-LP-PTX, respectively. The homing specificity of T7/TAT-LP was evaluated on the tumor spheroids, which revealed that T7/TAT-LP was more efficaciously internalized in tumor cells than TAT-LP, T7-LP and LP, respectively. Compared to LP, TAT-LP and T7-LP, T7/TAT-LP showed the strongest cell uptake property, and the highest accumulation ability in tumor spheroids in vitro. In the in vivo study, the T7/TAT-LP-PTX exhibited the best inhibitory effect of tumor growth for A549-bearing mice. Collectively, these results suggested that T7/TAT-LP-PTX is a promising drug delivery system for the treatment of lung cancer.

Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases.

Vascular diseases are the most prevalent diseases worldwide. This study intended to analyze peripheral blood miRNA levels and their correlation with NT-pro-BNP and cTN-I in patients with atherosclerosis or pre-atherosclerotic conditions to build a dynamic correlation between vascular diseases and their biomarkers. Serum NT-pro-BNP and cTN-I levels were measured by their respective ELISA kits. The miRNA levels were assayed by quantitative PCR. Unique miRNA signatures were identified for both atherosclerosis and pre-atherosclerosis. The levels of miR-92a, 126, 130a, 222, and 370 levels were decreased in the peripheral blood of pre-atherosclerotic subjects. In atherosclerosis, miR-21, 122, 130a, and 211 were significantly increased whereas miR-92a, 126, and 222 were markedly decreased. Serum levels of NT-pro-BNP and cTN-I correlated with each other and increased with the progression of atherosclerosis. Moreover, the levels of cTN-I and NT-pro-BNP were positively correlated with miR-21 and negatively correlated with miR-126. Integrating specific pattern of miRNA levels with NT-pro-BNP and/or cardiac troponin may improve the diagnosis of cardiovascular diseases.

[Study on the status of cognition among Parkinson's disease patients in Xi'an.].

OBJECTIVE: To study the characteristics and influencing factors of cognition on patients with Parkinson's disease (PD) in Xi'an in order to provide evidence for early recognition and treatment of cognitive impairment on PD patients. METHODS: Clinically defined PD patients from 7 hospitals in Xi'an from Jan. to Apr. 2007 were assessed with mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA) for whole cognitive function. Furthermore, Fuld object memory test (FOM) was used to assess delayed memory while rapid verbal retrieve (RVR) was used to assess language fluency. Digit span subtest was used to assess attention and building blocks was used to assess visual space function respectively. RESULTS: 100 PD patients were recruited, including 52 men and 48 women, from 43 to 86 years old (65.6 +/- 17.1). MMSE scores was used as the standard for Recognition, PD with cognitive impairment accounted for 16%. According to MOCA scores, with PD cognitive disturbances accounted for 83%. Ability for calculation, short-term memory, visual space function, abstract capability, attention and language fluency dysfunction were main cognitive disturbances of PD. Analysis from single factor logistic regression showed that education, age of onset and gender were closely related to the occurrence of cognitive impairment on PD patients. CONCLUSION: Cognitive impairment was common in PD. Ability of calculation, short-term memory, visual space function, abstract capability, attention and language fluency dysfunction were main cognitive disturbances of PD. Cognitive impairment of PD was more likely to occur with low degree of education, late onset of PD, and being female.

[The use of antiparkinsonism drugs in 92 cases in Xi'an city].

OBJECTIVE: To investigate the treatment status of antiparkinsonism in Xi'an. METHODS: Six general hospitals were randomly chosen in Xi'an and all Parkinson's disease (PD) patients were interviewed by questionnaire from Jan. 2007 to Apr. 2007. RESULTS: 92 PD outpatients were enrolled in, including 48 males and 44 females, from 43 to 86 years old (mean 65.6 +/- 17.1) with duration of the disease from 0.2 to 27.8 years (mean 4.4 +/- 9.4). The preference of the drug use from the patients were: 40 (43.5%) preferred taking levodopa, 25 (27.2%) with amantadine and/or trihexyphenidyl, 14 (15.2%) with levodopa and others, 4 (4.4%) with dopamine agonist and others, 2 (2.2%) with other drugs, 7 (7.6%) with no treatment. There were 69 (75.0%) patients onset with resting tremor, 15 (16.3%) with bradykinesia, 6 (6.5%) with rigidity, and 2 (2.2%) with unknown symptoms. There was no startically significant difference in anti-PD drugs among the patients onset with different symptoms (P > 0.05). 45 patients appeared the onset of disease before 65 years old and with no dementia, 47 onset after 65 with or without dementia. There was no significant difference of anti-PD drugs between the two groups (P > 0.05). Most patients initiated anti-PD treatment with levodopa but few of them chose dopamine agonist. According to the classification of Hoehn & Yahr, 25(27.2%)belonged to Grade I, 53 (57.6%) to Grade II, 8 (8.7%) to Grade III, 3 (3.3%) to Grade IV and 3 (3.3%) to Grade V. There was no significant differences of anti-PD drugs between different grades of the disease (P > 0.05). 55.3% of the patients changed their anti-PD drugs randomly during the therapy, but with no relation to their gender, age, educational level, dementia, the number of family members, course of diseases, or the degree of Hoehn & Yahr, frequency and categories of medicine. CONCLUSION: Anti-PD treatment in Xi'an did not strictly follow the standardized protocol, with few patients using dopamine agonist and over 50% of the patients changed their drugs randomly.

[The incidence of dementia among elderly people in Xi' an, China].

OBJECTIVE: To explore the incidence of dementia among elderly people in Xi'an and its related risk factors. METHODS: Subjects that had been studied on the prevalence of dementia were follow-up, and the incidence of dementia, Alzheimer disease (AD) , and vascular dementia (VD) were counted by person-years. The clinical diagnosis on dementia,AD and VD were based upon the 3rd Edition of Diagnostic and Statistical of Manual of Mental Disorder, Revised version (DSM-III-R) and NINCDS-ADRDA criteria. RESULTS: 2197 subjects of non-dementia being identified in 1998, were re-surveyed in 2001. Out of them, 47 new cases of dementia including 37 cases of AD and 8 cases of VD were identified, with an annual incidence rates of dementia, AD and VD as 0.68%, 0.54% and 0.12% among those of 55 years and over and 0.89%, 0.69% and 0.17% in 65 years and over, respectively. Analysis from single factor logistic regression showed that age and education but not gender were closely related to the occurrence of AD. On the contrary, age, hypertension and stroke were closely related to the occurrence of VD. CONCLUSION: The incidence of dementia in the "Xi' an cohort" was similar to that being reported from other countries. AD and VD were an age-related diseases but education seemed to have had great protective effect while lack of formal education served as risk factor to AD.