Chronic diseases spectrum and multimorbidity in elderly inpatients based on a 12-year epidemiological survey in China.

BACKGROUND: The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. METHODS: A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. RESULTS: A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. CONCLUSIONS: By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

A Highly Sensitive and Selective Near-Infrared Fluorescent Probe for Imaging Peroxynitrite in Living Cells and Drug-Induced Liver Injury Mice.

Drug-induced liver injury (DILI) is a major clinical issue associated with the majority of commercial drugs. During DILI, the peroxynitrite (ONOO-) level is upregulated in the liver. However, traditional methods are unable to timely monitor the dynamic changes of the ONOO- level during DILI in vivo. Therefore, ONOO--activated near-infrared (NIR) fluorescent probes with high sensitivity and selectivity are key to the early diagnosis of DILI in situ. Herein, we report a novel ONOO--responsive NIR fluorescent probe, QCy7-DP, which incorporates a donor-dual-acceptor π-electron cyanine skeleton with diphenyl phosphinate. The ONOO--mediated highly selective hydrolytic cleavage via an addition-elimination pathway of diphenyl phosphinate produced the deprotonated form of QCy7 in physiological conditions with a distinctive extended conjugated π-electron system and ∼200-fold enhancement in NIR fluorescence emission at 710 nm. Moreover, the probe QCy7-DP was successfully used for the imaging of the endogenous and exogenous ONOO- concentration changes in living cells. Importantly, in vivo fluorescence imaging tests demonstrated that the probe can effectively detect the endogenous generation of ONOO- in an acetaminophen (APAP)-induced liver injury mouse model. This study provides insight into the design of highly selective NIR fluorescent probes suitable for spatiotemporal monitoring of ONOO- under different pathological conditions.

Nonbone Marrow CD34+ Cells Are Crucial for Endothelial Repair of Injured Artery.

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Synthesis, Optical Properties, and Fluorescence Cell Imaging of Novel Mixed Fluorinated Subphthalocyanines.

Subphthalocyanines (SubPcs) are a kind of tripyrrolic macrocycle with a boron atom at their core. Incorporating different units onto the SubPc periphery can endow them with various unique properties. Herein, a series of novel fluorinated low-symmetry SubPc derivatives containing chlorine groups (F8-Cl4-SubPc, F4-Cl8-SubPc) and methoxy groups (F8-(OCH3)2-SubPc) were synthesized and characterized by spectral methods (MS, FT-IR, 1H, 13C, 11B, and 19F NMR spectroscopy), and the effect of the peripheral substituents on their electronic structure of low-symmetry macrocycle was investigated by cyclic voltammetry, theoretical calculation, electronic absorption, and emission spectroscopy. In contrast to perfluorinated SubPcs, these low-symmetry SubPcs revealed non-degenerate LUMO and LUMO + 1 orbitals, especially F8-(OCH3)2-SubPc, which was consistent with the split Q-band absorptions. The cyclic voltammetry revealed that these SubPcs exhibited two or three reduction waves and one oxidation wave, which is consistent with the reported SubPcs. Finally, an intracellular fluorescence imaging study of these compounds revealed that these compounds could enter cancer cells and be entrapped in the lysosomes, which provides a possibility of future applications in lysosome fluorescence imaging and targeting.

Synthesis of Renal-Clearable Multicolor Fluorescent Silicon Nanodots for Tumor Imaging and In Vivo H2O2 Profiling.

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H2O2 imaging in living cells and tissue through in situ reduction reaction-lighted fluorescence of the nanoprobe. Our results provide an invaluable methodology for the synthesis of renal-clearable multicolor SiNDs and their potential applications for fluorescence imaging and biomarker sensing. These SiNDs are also promising for various biological and biomedical applications.

TNF-α-Induce Protein 8-Like 1 Inhibits Hepatic Steatosis, Inflammation, and Fibrosis by Suppressing Polyubiquitination of Apoptosis Signal-Regulating Kinase 1.

BACKGROUND AND AIMS: Characterized by hepatocyte steatosis, inflammation, and fibrosis, NASH is a complicated process that contributes to end-stage liver disease and, eventually, HCC. TNF-α-induced protein 8-like 1 (TIPE1), a new member of the TNF-α-induced protein 8 family, has been explored in immunology and oncology research; but little is known about its role in metabolic diseases. APPROACH AND RESULTS: Here, we show that hepatocyte-specific deletion of TIPE1 exacerbated diet-induced hepatic steatosis, inflammation, and fibrosis as well as systemic metabolic disorders during NASH pathogenesis. Conversely, hepatocyte-specific overexpression of TIPE1 dramatically prevented the progression of these abnormalities. Mechanically, TIPE1 directly interacted with apoptosis signal-regulating kinase 1 (ASK1) to suppress its TNF receptor-associated factor 6 (TRAF6)-catalyzed polyubiquitination activation upon metabolic challenge, thereby inhibiting the downstream c-Jun N-terminal kinase and p38 signaling pathway. Importantly, dramatically reduced TIPE1 expression was observed in the livers of patients with NAFLD, suggesting that TIPE1 might be a promising therapeutic target for NAFLD and related metabolic diseases. CONCLUSIONS: TIPE1 protects against hepatic steatosis, inflammation, and fibrosis through directly binding ASK1 and restraining its TRAF6-catalyzed polyubiquitination during the development of NASH. Therefore, targeting TIPE1 could be a promising therapeutic approach for NAFLD treatment.

Self-compassion and fear of cancer recurrence in Chinese breast cancer patients: The mediating role of maladaptive cognitive styles.

OBJECTIVES: Previous studies have examined the benefits of self-compassion for psychological symptoms in breast cancer patients; however, little is known about the role of self-compassion for patients' fear of cancer recurrence (FCR) as well as the underlying mediating mechanisms. This study aimed to examine the effect of self-compassion on FCR, and whether maladaptive cognitive styles mediate this relationship. METHODS: This cross-sectional study included 304 females with breast cancer. A self-report questionnaire was used to assess patients' self-compassion, maladaptive cognitive styles (i.e., rumination and catastrophising), and FCR. Parallel mediation analyses were conducted to examine the research questions. RESULTS: Approximately half of the patients with breast cancer reported elevated levels of FCR. Self-compassion was negatively related to FCR, and the relationship between self-compassion and FCR was mediated by catastrophising, whereas rumination did not significantly mediate the relationship between self-compassion and FCR. CONCLUSIONS: Our findings suggest that self-compassion and catastrophising are closely associated with FCR in patients with breast cancer, and catastrophising is a mediator between self-compassion and FCR. Clinicians could reduce breast cancer patients' FCR by enhancing their self-compassion and improving their maladaptive cognitive styles.

Near infrared imaging of intracellular GSH by AuNCs@MnO2 core-shell nanoparticles based on the absorption competition mechanism.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 µM with a detection limit of 0.67 µM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

Association between epicardial adipose tissue and blood pressure: A systematic review and meta-analysis.

AIMS: Epicardial adipose tissue has been reported to be associated with the development of cardiometabolic disease. Whether this is true for hypertension and non-dipper blood pressure remains controversial. Here, we conducted a systemic review and meta-analysis to evaluate the association between EAT and blood pressure. DATA SYNTHESIS: Pubmed, Embase, and Web of Science were searched for relevant papers. Studies reported on the difference of EAT thickness between hypertensive and normotensive patients, or those recorded odds ratio (OR) between EAT and hypertension were included. The standard mean difference (SMD) and ORs were extracted and pooled using a random-effects model respectively. We further assessed the effect of EAT on circadian rhythm of blood pressure by combining multiple-adjusted ORs for non-dipper blood pressure. Seven studies with an overall sample of 1089 patients reported the mean difference of EAT thickness between hypertensive and normotensive patients, and the hypertensive patients had higher EAT (SMD = 1.07; 95% CI: 0.66-1.48; I2 = 89.2%) compared with controls. However, the pooled association between EAT and hypertension from two studies was not significant (OR = 1.65, 95%CI 0.62-4.68; I2 = 87.5%). The summary risk effect of EAT on non-dipper blood pressure from six studies comprising1208 patients showed that each 1 mm increment of EAT was associated with a 2.55-fold risk of non-dipper blood pressure. CONCLUSION: Hypertensive patients tend to present higher EAT thickness near the right ventricular wall and increased EAT thickness might be associated with high risk of non-dipper blood pressure. Future researches are warranted to determine the causal link between EAT and hypertension and the underlying mechanism.

Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway.

BACKGROUND: Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR. METHODS: High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting. RESULTS: GLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1ß, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo. CONCLUSION: GLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.

MicroRNA-124 regulates cardiomyocyte apoptosis and myocardial infarction through targeting Dhcr24.

AIMS: microRNA-124(miR-124) has recently been reported to be elevated in cardiovascular disease. In this study, we aimed to investigate the exact role of miR-124 in cardiomyocytes and myocardial infarction, identifying the functional target and its regulatory mechanisms. METHODS AND RESULTS: Cultured cardiomyocytes, myocardial-infarction mouse model, and clinical data were used to study the effects of miR-124 on myocardial ischemia. Expression of miR-124 was up-regulated in H2O2 and hypoxia induced cardiomyocyte injury. miR-124 over-expression significantly increased cardiomyocyte apoptosis, whereas miR-124 inhibition attenuated cell death. 3ß-hydroxysteroid-Delta24 reductase (Dhcr24), a multi-functional enzyme implicated in cholesterol synthesis and various diseases, was identified as a novel functional target of miR-124 in cardiac myocytes. The miR-124-Dhcr24 axis was responsible for cardiomyocyte apoptosis regulation. Furthermore, myocardial infarction induced miR-124 activation and Dhcr24 reduction in vivo. Modulation of miR-124 by intra-myocardial injection of agomiR or antagomiR was capable of manipulating cardiomyocyte apoptosis and myocardial infarction in mice. More importantly, circulating miR-124 was also observed to be elevated in acute myocardial infarction (AMI) patients and was correlated with myocardial injury and cardiac function. CONCLUSION: Our findings strongly demonstrated that miR-124 targeting Dhcr24 regulates oxidative stress and hypoxia induced cardiomyocyte apoptosis and myocardial infarction. The miR-124-Dhcr24 axis could be a potential biomarker as well as the therapeutic target for AMI.

Effect of Hydrophobicity on Nano-Bio Interactions of Zwitterionic Luminescent Gold Nanoparticles at the Cellular Level.

Fundamental understanding of how the hydrophobicity impacts cellular interactions of engineered nanoparticles is critical to their future success in healthcare. Herein, we report that inserting hydrophobic octanethiol onto the surface of zwitterionic luminescent glutathione coated gold nanoparticles (GS-AuNPs) of 2 nm enhanced their affinity to the cellular membrane and increased cellular uptake kinetics by more than one order of magnitude, rather than inducing the accumulation of the AuNPs in the bilayer core or enhancing their passive diffusion. These studies highlight the diversity and heterogeneity in the hydrophobicity-induced nano-bio interactions at the cellular level and offer a new pathway to expediting cellular uptake of engineered nanoparticles. In addition, the amphiphilic luminescent AuNPs with high affinity to cell membrane and rapid endocytosis potentially serve as dual-modality imaging probes to correlate fluorescence and electron microscopies at the cellular level.

Improved endogenous epoxyeicosatrienoic acid production mends heart function via increased PGC 1α-mitochondrial functions in metabolic syndrome.

Metabolic syndrome (MS) is a combination of symptoms characterized by central obesity, hypertension, hyperglycemia, and hyperlipidemia, which together increase the risk of heart disease, stroke and diabetes. In our study, we hypothesized that an EET-agonist (AUDA) would increase expression of PGC 1α and improve mitochondrial and endothelial functions, resulting in improved heart function in a rat model of MS. To investigate this, rats were randomly divided into four groups: 1) Control; 2) MS + ABCT; 3) MS + AUDA; and 4) MS + AUDA + SnMP. MS rats were fed a high-fructose diet for 16 weeks and developed elevated inflammatory mediators, oxidative stress, and significant decreases in fractional shortening and hemodynamic parameters, indicating cardiac dysfunction. Histology revealed myocardial fibrosis and myocyte hypertrophy. AUDA improves mitochondrial function proven by increase in mt copy number and ATP production and significantly increased expression of PGC-1α and HO-1 in the rats and normalization of inflammatory cytokines, oxidative stress, and improves in cardiac function and myocardial fibrosis. These benefits were reversed by SnMP. Furthermore, AUDA increases eNOS but decreases iNOS expression which improved endothelial function. We therefore demonstrate that endogenous EET upregulation plays a novel role in protecting the heart from MS by regulating mitochondrial and endothelial function.

Assessment of left ventricular systolic and diastolic abnormalities in patients with hypertrophic cardiomyopathy using real-time three-dimensional echocardiography and two-dimensional speckle tracking imaging.

BACKGROUND: Conventional echocardiography is not sensitive enough to assess left ventricular (LV) dysfunction in hypertrophic cardiomyopathy (HCM) patients. This research attempts to find a new ultrasonic technology to better assess LV diastolic function, systolic function, and myocardial longitudinal and circumferential systolic strain of segments with different thicknesses in HCM patients. METHODS: This study included 50 patients with HCM and 40 healthy subjects as controls. The peak early and late mitral annulus diastolic velocities at six loci (Ea' and Aa', respectively) and the Ea'/Aa' ratio were measured using real-time tri-plane echocardiography and quantitative tissue velocity imaging (RT-3PE-QTVI). The mean value of Ea' at six loci (Em') was obtained for the calculation of E/Em' ratio. The LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV stroke volume (LVSV), and LV ejection fraction (LVEF) were measured using real-time three-dimensional echocardiography (RT-3DE). LV myocardial longitudinal peak systolic strain (LPSS) and circumferential peak systolic strain (CPSS) in the apical-middle-basal segments (LPSS-api, LPSS-mid, LPSS-bas; CPSS-api, CPSS-mid, and CPSS-bas, respectively) were obtained using a software for two-dimensional speckle tracking imaging (2D-STI). According to the different segmental thicknesses (STs) in each HCM patient, the values (LPSS and CPSS) of all the myocardial segments were categorized into three groups and the respective averages were computed. RESULTS: The Ea', Aa', and, Ea'/Aa' ratio in HCM patients were lower than those in the controls (all p < 0.001), while the E/Em' ratio in HCM patients was higher than that in the controls (p < 0.001). The LVEDV, LVSV, and LVEF were significantly lower in HCM patients than in controls (all p < 0.001). In HCM patients, the LPSS-api, LPSS-mid, LPSS-bas, CPSS-api, CPSS-mid, and CPSS-bas and the LPSS and CPSS of LV segments with different thicknesses were all significantly reduced (all p < 0.001). CONCLUSIONS: In HCM patients, myocardial dysfunction was widespread not only in the obviously hypertrophic segments but also in the non-hypertrophic segments; the LV systolic and diastolic functions were damaged, even with a normal LVEF. LV diastolic dysfunction, systolic dysfunction, and myocardial deformation impairment in HCM patients can be sensitively revealed by RT-3PE-QTVI, RT-3DE, and 2D-STI.

Headache disorder and the risk of dementia: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Until now, headache disorders have not been established as a risk factor for dementia. The aim of this study was to determine whether headache was associated with an increased risk of dementia. METHODS: We systematically searched electronic databases, including PubMed, Embase, and Web of Science, for studies investigating the association between headache and dementia. We then conducted a meta-analysis to determine a pooled-effect estimate of the association. RESULTS: We identified 6 studies (covering 291,549 individuals) to investigate the association between headache and the risk of all-cause dementia or Alzheimer's disease (AD). Pooled analyses showed that any headache was associated with a 24% greater risk of all-cause dementia (relative risk [RR] = 1.24; 95% confidential interval [CI]: 1.09-1.41; P = 0.001), and that any headache was not statistically significantly associated with an increased risk of AD (RR = 1.47; 95% CI: 0.82-2.63; P = 0.192). CONCLUSIONS: Our results indicated that any headache was associated with an increased risk of all-cause dementia. However, additional studies are warranted to further confirm and understand the association.

Interactions of Renal-Clearable Gold Nanoparticles with Tumor Microenvironments: Vasculature and Acidity Effects.

The success of nanomedicines in the clinic depends on our comprehensive understanding of nano-bio interactions in tumor microenvironments, which are characterized by dense leaky microvasculature and acidic extracellular pH (pHe ) values. Herein, we investigated the accumulation of ultrasmall renal-clearable gold NPs (AuNPs) with and without acidity targeting in xenograft mouse models of two prostate cancer types, PC-3 and LNCaP, with distinct microenvironments. Our results show that both sets of AuNPs could easily penetrate into the tumors but their uptake and retention were mainly dictated by the tumor microvasculature and the enhanced permeability and retention effect over the entire targeting process. On the other hand, increased tumor acidity indeed enhanced the uptake of AuNPs with acidity targeting, but only for a limited period of time. By making use of simple surface chemistry, these two effects can be synchronized in time for high tumor targeting, opening new possibilities to further improve the targeting efficiencies of nanomedicines.

A Novel and Simple Method for the Synthesis of ß-SiC/SiO2 Coaxial Nanocables in a Large Area: Polycarbosilane Pyrolysis.

In the present work, ß-SiC/SiO2 coaxial nanocables are synthesized in a large area via direct pyrolysis of polymeric precursor method, in which, polycarbosilane acts the single raw material. The morphology, chemical composition and detailed microstructure of the nanocables are characterized. The core of nanocables are single crystalline ß-SiC nanowires with diameter of 30 - 60 nm grown along [111] direction. The uniform coating layer is amorphous SiO2 with thickness of 15 nm. Based on the pyrolysis process of polycarbosilane, the Vapor-Liquid-Solid growth mechanism is discussed. Furthermore, field emission measurements show the turn-on field and the threshold field are 3.2 V/µm and 6.5 V/µm, respectively. This study shows that ß-SiC/SiO2 coaxial nanocables are promising for field emission display device and other vacuum electronic devices.

Dimerization of Organic Dyes on Luminescent Gold Nanoparticles for Ratiometric pH Sensing.

Synergistic effects arising from the conjugation of organic dyes onto non-luminescent metal nanoparticles (NPs) have greatly broadened their applications in both imaging and sensing. Herein, we report that conjugation of a well-known pH-insensitive dye, tetramethyl-rhodamine (TAMRA), to pH-insensitive luminescent gold nanoparticles (AuNPs) can lead to an ultrasmall nanoindicator that can fluorescently report local pH in a ratiometric way. Such synergy originated from the dimerization of TAMRA on AuNPs, of which geometry was very sensitive to surface charges of the AuNPs and can be reversely modulated through protonation of surrounding glutathione ligands. Not limited to pH-insensitive dyes, this pH-dependent dimerization can also enhance the pH sensitivity of fluorescein, a well-known pH-sensitive dye, within a larger pH range, opening up a new pathway to design ultrasmall fluorescent ratiometric nanoindicators with tunable wavelengths and pH response ranges.

Renal clearance and degradation of glutathione-coated copper nanoparticles.

Degradation of inorganic nanoparticles (NPs) into small molecular complexes is often observed in the physiological environment; however, how this process influences renal clearance of inorganic NPs is largely unknown. By systematically comparing renal clearance of degradable luminescent glutathione coated copper NPs (GS-CuNPs) and their dissociated products, Cu(II)-glutathione disulfide (GSSG) complexes (Cu(II)-GSSG), we found that GS-CuNPs were eliminated through the urinary system surprisingly faster and accumulated in the liver much less than their smaller dissociation counterparts. With assistance of radiochemistry and positron emission tomography (PET) imaging, we found that the observed "nano size" effect in enhancing renal clearance is attributed to the fact that GS-CuNPs are more resistant to serum protein adsorption than Cu(II)-GSSG. In addition, since dissociation of GS-CuNPs follows zero-order chemical kinetics, their renal clearance and biodistribution also depend on initial injection doses and their dissociation processes. Quantitative understanding of size effect and other factors involved in renal clearance and biodistribution of degradable inorganic NPs will lay down a foundation for further development of renal-clearable inorganic NPs with minimized nanotoxicity.

Protective Effect of L-Theanine on Cadmium-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondria-Mediated Pathway.

L-Theanine is an amino acid derivative from green tea. The present work was aimed at the effect of L-theanine on neuron-like rat pheochromocytoma (PC12) cells stimulated with cadmium chloride. Treatment with L-theanine before cadmium exposure increased cell viability; the experiments of Annexin V/PI staining indicated that L-theanine inhibited cadmium-induced cell apoptosis. Meanwhile, L-theanine decreased ROS production and protected from cadmium-induced disruption of mitochondrial transmembrane potential. Compared with cadmium-treated cells, L-theanine could also decrease the ratio of Bax/Bcl-2, as well as the level of cleaved caspase-9, caspase-3 and poly(ADP-ribose) polymerase. Furthermore, L-theanine depresses cadmium-induced up regulation of phosphorylations of PI3K/Akt, MAPK ERK1/2, and JNK signaling. These data suggest that L-theanine pretreatment reduces severity of cadmium toxicity probably via antioxidant action. Therefore, it may be concluded that L-theanine could be exploited for prevention of cadmium-induced diseases.