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BACKGROUND: There is growing interest in the joint effects of hazardous trace elements (HTEs) on lung function deficits, but the data are limited. This is a critical research gap given increased global industrialisation. METHODS: A national cross-sectional study including spirometry was performed among 2112 adults across 11 provinces in China between 2020 and 2021. A total of 27 HTEs were quantified from urine samples. Generalised linear models and quantile-based g-computation were used to explore the individual and joint effects of urinary HTEs on lung function, respectively. RESULTS: Overall, there were negative associations between forced expiratory volume in 1 s (FEV1) and urinary arsenic (As) (z-score coefficient, -0.150; 95% CI, -0.262 to -0.038 per 1 ln-unit increase), barium (Ba) (-0.148, 95% CI: -0.258 to -0.039), cadmium (Cd) (-0.132, 95% CI: -0.236 to -0.028), thallium (Tl) (-0.137, 95% CI: -0.257 to -0.018), strontium (Sr) (-0.147, 95% CI: -0.273 to -0.022) and lead (Pb) (-0.121, 95% CI: -0.219 to -0.023). Similar results were observed for forced vital capacity (FVC) with urinary As, Ba and Pb and FEV1/FVC with titanium (Ti), As, Sr, Cd, Tl and Pb. We found borderline associations between the ln-quartile of joint HTEs and decreased FEV1 (-20 mL, 95% CI: -48 to +8) and FVC (-14 mL, 95% CI: -49 to+2). Ba and Ti were assigned the largest negative weights for FEV1 and FVC within the model, respectively. CONCLUSION: Our study investigating a wide range of HTEs in a highly polluted setting suggests that higher urinary HTE concentrations are associated with lower lung function, especially for emerging Ti and Ba, which need to be monitored or regulated to improve lung health.
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Exposição Ambiental , Oligoelementos , Humanos , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , China/epidemiologia , Oligoelementos/urina , Adulto , Volume Expiratório Forçado , Espirometria , Capacidade Vital , Pulmão/fisiopatologia , IdosoRESUMO
Nanotheranostic platforms integrated with diagnostic and therapeutic functions have been widely developed for tumor medicine. However, the "always-on" nanotheranostic platforms suffer from poor tumor specificity, which may largely restrict therapeutic efficacy and prevent precise theranostics. Here, we develop an in situ transformable pro-nanotheranostic platform (ZnS/Cu2O@ZIF-8@PVP) by encapsulating ZnS and Cu2O nanoparticles in a metal-organic framework (MOF) nanomaterial of ZIF-8 that allows activable photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) of tumors in vivo. It is shown that the pro-nanotheranostic platform gradually decomposes and releases ZnS nanoparticles and Cu+ ions in acidic conditions, which spontaneously trigger a cation exchange reaction and synthesize Cu2S nanodots in situ with activated PA signals and PTT effects. Moreover, the excessive Cu+ ions function as Fenton-like catalysts and catalyze the production of highly reactive hydroxyl radicals (â¢OH) for CDT using elevated levels of H2O2 in tumor microenvironments (TMEs). In vivo studies demonstrate that the in situ transformable pro-nanotheranostic platform can specifically image tumors via PA and photothermal imaging and efficiently ablate tumors through synergistic CDT/PTT. Our in situ transformable pro-nanotheranostic platform could provide a new arsenal for precise theranostics in cancer therapy.
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Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Nanomedicina Teranóstica/métodos , Técnicas Fotoacústicas/métodos , Peróxido de Hidrogênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Objective: The industrial production and combustion of coal can produce silica nanoparticles (nano-SiO2). It enters the human body mainly through the respiratory tract and exerts a toxic effect. However, whether nano-SiO2 can increase the IL-1ß-induced inflammatory expression in A549 cells has not been tested. Therefore, the synergistic toxicity of nano-SiO2 and IL-1ß to A549 was observed in our study. Materials and methods: We exposed A549 cells to nano-SiO2 (0, 100, 500, and 1000 µg/ml) for 12 and 24 h. The effect of nano-SiO2 on the viability of A549 cells was observed by the CCK-8 method. The A549 cells were exposed to nano-SiO2 (1 mg/mL) and cytokine IL-1ß (10 ng/mL) for 4 h, and we detected the expression of IL-1ß and IL-6 cytokines by real time quantitative polymerase chain (RT-qPCR) and enzyme linked immunosorbent assay (ELISA). The expression of ß-Actin, I-κB, phospho-ERK1/2 (P-ERK1/2), total-ERK1/2 (T-ERK1/2), phospho-JNK (P-JNK), total-JNK (T-JNK), phospho-P38 (P-P38), and total-P38 (T-P38) in A549 cells was detected by the Western Blot method. Results: The nano-SiO2 treatment resulted in a time-dependent decrease in the viability of A549 cells. The synergistic effect of nano-SiO2 and IL-1ß was observed on the new production of IL-1ß and IL-6 in A549 cells. The Western blot results showed that nano-SiO2 can increase the expression of IL-1ß and IL-6 by promoting the phosphorylation of ERK1/2 and elevating the phosphorylation of I-κB by IL-1ß. IL-1ß and IL-6 were induced by nano-SiO2, and the IL-1ß treatment with 20 µM of I-κBα phosphorylation inhibitor (PD98059) and 20 µM of ERK1/2 inhibitor (BAY11-7082) for 1 h was significantly lower than that of the control group in A549 cells. Discussion and conclusion: These results indicated that nano-SiO2 had a toxic effect on A549 cells, and this effect could increase IL-1ß on the A549 cell-induced inflammatory response. The results suggested that the release of IL-1ß and IL-6 in A549 was enhanced by the synergistic IL-1ß-induced phosphorylation of ERK1/2 and I-κB. This process is similar to a snowball, and it is possible that IL-1ß is continuously produced and repeatedly superimposed in A549 cells to produce an inflammatory effect; then, a vicious circle occurs, and an inflammatory storm is accelerated.
Assuntos
Interleucina-1beta/toxicidade , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Nanopartículas/efeitos adversos , Dióxido de Silício/toxicidade , Células A549 , Humanos , Inflamação/induzido quimicamente , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/imunologia , Interleucina-6/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Proteína Quinase 1 Ativada por Mitógeno/imunologia , Proteína Quinase 3 Ativada por Mitógeno/imunologia , Fatores de TempoRESUMO
Fabrication of clinically translatable nanoparticles (NPs) as photothermal therapy (PTT) agents against cancer is becoming increasingly desirable, but still challenging, especially in facile and controllable synthesis of biocompatible NPs with high photothermal efficiency. A new strategy which uses protein as both a template and a sulfur provider is proposed for facile, cost-effective, and large-scale construction of biocompatible metal sulfide NPs with controlled structure and high photothermal efficiency. Upon mixing proteins and metal ions under alkaline conditions, the metal ions can be rapidly coordinated via a biuret-reaction like process. In the presence of alkali, the inert disulfide bonds of S-rich proteins can be activated to react with metal ions and generate metal sulfide NPs under gentle conditions. As a template, the protein can confine and regulate the nucleation and growth of the metal sulfide NPs within the protein formed cavities. Thus, the obtained metal sulfides such as Ag2 S, Bi2 S3 , CdS, and CuS NPs are all with small size and coated with proteins, affording them biocompatible surfaces. As a model material, CuS NPs are evaluated as a PTT agent for cancer treatment. They exhibit high photothermal efficiency, high stability, water solubility, and good biocompatibility, making them an excellent PTT agent against tumors. This work paves a new avenue toward the synthesis of structure-controlled and biocompatible metal sulfide NPs, which can find wide applications in biomedical fields.
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Proteínas/química , Sulfetos/química , Enxofre/química , Compostos de Cádmio/química , Cobre/química , Nanopartículas Metálicas/química , Fototerapia/métodos , Prata/química , SolubilidadeRESUMO
Type 2 diabetes mellitus (T2DM) is a major global health problem. The rate of infection with Toxoplasma gondii (T. gondii) is more than one-third of the total world population. The effects of T. gondii infection on the risk of diabetic complications and comorbidities are unclear. This study aims to determine the relationship between T. gondii infection and complications of T2DM in the Han Chinese population. We collected 1580 blood samples from T2DM patients and measured the levels of specific IgG antibodies against T. gondii in the sera of these patients using an ELISA assay. A logistic regression analysis was performed to estimate the effect of T. gondii infection on the complications of T2DM, while adjusting for age, gender, and triglyceride level (TG). We applied the multifactor dimensionality reduction (MDR) method to detect the interactions between T. gondii infections, demographic indexes and biochemical indicators among the different complications. Gender (the odds ratio (OR) = 0.63, 95%CI =0.45-0.89, P = 0.008) and TG level (OR = 0.64, 95%CI =0.45-0.89, P = 0.009) were influencing factors in T. gondii infections. T2DM patients who were infected with T. gondii had a 2.34 times risk of developing hypertension than those patients without T. gondii infection (OR = 2.34, 95%CI = 1.12-4.88, P = 0.024). The multiplicative interaction analysis and the additive interaction analysis did not reveal any evidence of interactive effects on diabetic complications and comorbidities. T. gondii might be a factor associated with hypertension in T2DM patients.
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Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/parasitologia , Hipertensão/parasitologia , Toxoplasma , Toxoplasmose/complicações , Adulto , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Toxoplasma/imunologia , Toxoplasmose/imunologiaRESUMO
Herein, a novel tunable electrocatalytic nanobiointerface for the construction of a high-sensitivity and high-selectivity biofuel-cell (BFC)-based self-powered biosensor for the detection of transcription factor protein p53 is reported, in which bilirubin oxidase (BOD)/DNA supramolecular modified graphene/platinum nanoparticles hybrid nanosheet (GPNHN) works as a new enhanced material of biocathode to control the attachment of target, and thus tune the electron-transfer process of oxygen reduction for transducing signaling magnification. It is found that in the presence of p53, the strong interaction between the wild-type p53 and its consensus DNA sequence on the electrode surface can block the electron transfer from the BOD to the electrode, thus providing a good opportunity for reducing the electrocatalytic activity of oxygen reduction in the biocathode. This in combination with the glucose oxidation at the carbon nanotube/Meldola's blue/glucose dehydrogenase bioanode can result in a current/or power decrease of BFC in the presence of wild-type p53. The specially designed BFC-based self-powered p53 sensor shows a wide linear range from 1â pM to 1â µM with a detection limit of 1â pM for analyzing wild-type p53. Most importantly, our BFC-based self-powered sensors can detect the concentrations of wild-type p53 in normal and cancer cell lysates without any extensive sample pretreatment/separation or specialized instruments. The present BFC-based self-powered sensor can provide a simple, economical, sensitive, and rapid way for analyzing p53 protein in normal and cancer cells at clinical level, which shows great potential for creating the treatment modalities that capitalize on the concentration variation of the wild-type p53.
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Proteínas Reguladoras de Apoptose/química , Enzimas Imobilizadas/química , Glucose Oxidase/química , Nanopartículas/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Fatores de Transcrição/química , Proteínas Reguladoras de Apoptose/metabolismo , Fontes de Energia Bioelétrica , Técnicas Biossensoriais , Transporte de Elétrons , Enzimas Imobilizadas/metabolismo , Glucose Oxidase/metabolismo , Limite de Detecção , Nanotubos de Carbono , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismo , Fatores de Transcrição/metabolismoRESUMO
We demonstrated a biofuel cells (BFCs)-based self-powered sensing system for the detection of Nε-(carboxymethyl)lysine (CML), in which the bilirubin oxidase (BOD)-carbon nanotube (CNT) bioconjugate modified with antibody acted as a biocatalyst for enhancing O2 reduction in the biocathode, as well as the transducing enzyme for signaling magnification. With an increase in the concentration of CML, the amount of BOD labels on biocathode surface increases, thus leading to the higher output of the as-prepared BFCs. This novel BFCs-based self-powered sensor showed a wide linear range for analyzing CML from 1 nM to 100 µM with a detection limit of 0.2 nM, which was 50 times more sensitive than that determined from the conventional ELISA. Most importantly, our new self-powered sensing platform can determine the level of CML in serum samples from multiple healthy donors and multiple sclerosis patients, being well in accordance with that from the commercial ELISA analysis.
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Fontes de Energia Bioelétrica , Imunoensaio , Lisina/análogos & derivados , Nanotubos de Carbono/química , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/química , Ensaio de Imunoadsorção Enzimática , Lisina/análise , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/metabolismoRESUMO
Climate change has a discernible influence on rainfall patterns, thus potentially affecting the intricate dynamics of soil respiration (Rs) and soil carbon storage. However, we still lack a profound understanding of the determinants of Rs response to rainfall events. Here, utilizing a comprehensive 10-year dataset (2004-2013), we explored the direction and magnitude of Rs response to rainfall events and the underlying determinants in a temperate forest. Based on the identified 368 rainfall events over the study period, we demonstrate that rainfall suppresses Rs when the soil moisture is optimal and moist in the growing season, whereas its effect on Rs during the non-growing season is minimal. Notably, antecedent soil moisture, rather than rainfall amount, shows a substantial impact on Rs during the growing season (coefficient of determination (R2) = 0.37 for antecedent soil moisture, and R2 < 0.01 for rainfall amount). Incorporating antecedent soil moisture significantly enhances the explanatory power (R2) from 0.09 to 0.45 regarding the relative changes in Rs following rainfall events. Our results highlight the environmental dependency of Rs response to rainfall events and suggest that incorporating the role of antecedent soil moisture could enhance predictability and reduce uncertainty in ecosystem modeling.
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Flash droughts characterized by rapid onset and intensification are expected to be a new normal under climate change and potentially affect vegetation photosynthesis and terrestrial carbon sink. However, the effects of flash drought on vegetation photosynthesis and their potential dominant driving factors remain uncertain. Here, we quantify the susceptibility and response magnitude of vegetation photosynthesis to flash drought across different ecosystems (i.e., forest, shrubland, grassland, and cropland) in China based on reanalysis and satellite observations. By employing the extreme gradient boosting model, we also identify the dominant factors that influence these flash drought-photosynthesis relationships. We show that over 51.46 % of ecosystems across China are susceptible to flash drought, and grasslands are substantially suppressed, as reflected in both sensitivity and response magnitude (with median gross primary productivity anomalies of -0.13). We further demonstrate that background climate differences (e.g., mean annual temperature and aridity) predominantly regulate the response variation in forest and shrubland, with hotter/colder or drier ecosystems being more severely suppressed by flash drought. However, in grasslands and croplands, the differential vegetation responses are attributed to the intensity of abnormal hydro-meteorological conditions during flash drought (e.g., vapor pressure deficit (VPD) and temperature anomalies). The effects of flash droughts intensify with increasing VPD and nonmonotonically relate to temperature, with colder or hotter temperatures leading to more severe vegetation loss. Our results identify the vulnerable ecological regions under flash drought and enable a better understanding of vegetation photosynthesis response to climate extremes, which may be useful for developing effective management strategies.
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Mudança Climática , Secas , Ecossistema , Fotossíntese , China , FlorestasRESUMO
Chimeric antigen receptor (CAR) T cells show suboptimal efficacy in acute myeloid leukemia (AML). We find that CAR T cells exposed to myeloid leukemia show impaired activation and cytolytic function, accompanied by impaired antigen receptor downstream calcium, ZAP70, ERK, and C-JUN signaling, compared to those exposed to B-cell leukemia. These defects are caused in part by the high expression of CD155 by AML. Overexpressing C-JUN, but not other antigen receptor downstream components, maximally restores anti-tumor function. C-JUN overexpression increases costimulatory molecules and cytokines through reinvigoration of ERK or transcriptional activation, independent of anti-exhaustion. We conduct an open-label, non-randomized, single-arm, phase I trial of C-JUN-overexpressing CAR-T in AML (NCT04835519) with safety and efficacy as primary and secondary endpoints, respectively. Of the four patients treated, one has grade 4 (dose-limiting toxicity) and three have grade 1-2 cytokine release syndrome. Two patients have no detectable bone marrow blasts and one patient has blast reduction after treatment. Thus, overexpressing C-JUN endows CAR-T efficacy in AML.
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Imunoterapia Adotiva , Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-jun , Receptores de Antígenos Quiméricos , Humanos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Proteínas Proto-Oncogênicas c-jun/metabolismo , Animais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Idoso , Adulto , Linhagem Celular Tumoral , CamundongosRESUMO
Folate receptor alpha (FOLR1) is vital for cells ingesting folate (FA). FA plays an indispensable role in cell proliferation and survival. However, it is not clear whether the axis of FOLR1/FA has a similar function in viral replication. In this study, we used vesicular stomatitis virus (VSV) to investigate the relationship between FOLR1-mediated FA deficiency and viral replication, as well as the underlying mechanisms. We discovered that FOLR1 upregulation led to the deficiency of FA in HeLa cells and mice. Meanwhile, VSV replication was notably suppressed by FOLR1 overexpression, and this antiviral activity was related to FA deficiency. Mechanistically, FA deficiency mainly upregulated apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B) expression, which suppressed VSV replication in vitro and in vivo. In addition, methotrexate (MTX), an FA metabolism inhibitor, effectively inhibited VSV replication by enhancing the expression of APOBEC3B in vitro and in vivo. Overall, our present study provided a new perspective for the role of FA metabolism in viral infections and highlights the potential of MTX as a broad-spectrum antiviral agent against RNA viruses.
Assuntos
Receptor 1 de Folato , Vírus da Estomatite Vesicular Indiana , Humanos , Animais , Camundongos , Células HeLa , Receptor 1 de Folato/farmacologia , Vírus da Estomatite Vesicular Indiana/genética , Antivirais/farmacologia , Replicação Viral , Ácido Fólico/farmacologia , Citidina Desaminase/genética , Antígenos de Histocompatibilidade Menor/genética , Antígenos de Histocompatibilidade Menor/farmacologia , Desaminases APOBECRESUMO
OBJECTIVE: To examine the relationship between inflammation and the comorbidity of mental disorders with irritable bowel syndrome (IBS) by comparing intestinal mucosa inflammatory biomarkers in patients with and without mental disorders. METHODS: A total of 43 consecutive IBS patients fulfilling the Rome III criteria and 15 volunteers serving as controls without digestive symptoms were recruited and interviewed with Composite International Diagnostic Interview (CIDI) by the well-trained staff and thus classified as with or without mental disorders. All subjects underwent colonoscopy and biopsies were acquired from the mucosa of distal ileum and colon. CD3(+) lymphocytes, mast cells, 5-HT positive cells and (indoleamine 2,3-dioxygenase) IDO positive cells were identified immunohistologically in mucosa biopsies in volunteers (n = 13), IBS patients without mental disorder (n = 24) and IBS patients with mental disorder (n = 19). RESULTS: The incidence of mental disorders in IBS patients was significantly higher than that in the volunteers (19/43 vs 2/15, P = 0.012), including 9 patients with anxiety disorders and 8 with mood disorders. (1) The number of mast cells in IBS patients with mental disorder and that in IBS patients without mental disorder has no statistical significance ((16.7 ± 3.6)/HP vs (15.4 ± 3.1)/HP in distal ileum, (12.8 ± 2.2)/HP vs (12.3 ± 2.5)/HP in sigmoid, both P > 0.05). Similar results were seen in 5-HT positive cells ((3.7 ± 0.9)/HP vs (3.4 ± 0.8)/HP in distal ileum, (6.1 ± 1.8)/HP vs (5.2 ± 1.8)/HP in sigmoid, both P > 0.05). In distal ileum, the number of CD3(+) cells in IBS patients with mental disorder has no statistical significance with that in the IBS patients without mental disorder ((62 ± 16)/HP vs (55 ± 22)/HP, P > 0.05). Similar results were seen in IDO positive cells (6(2, 8)/HP vs 2(1, 5)/HP, P > 0.05). (2) The number of IDO positive cells from distal ileum in IBS patients with anxiety disorder was significantly higher than that in the IBS patients without mental disorder (6 (4,8) vs 2 (1,5), P = 0.018). The number of mast cells from distal ileum in the IBS patients with mood disorder were significantly higher than that in those without mental disorders ((18.3 ± 3.2)/HP vs (15.4 ± 3.1)/HP, P = 0.032). CONCLUSIONS: Mental disorders in the IBS patients may be associated with intestinal mucosal inflammation. The activation of IDO may cause the comorbidity of IBS with anxiety disorder while the activation of mast cells probably leads to the comorbidity of IBS with mood disorder.
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Inflamação/epidemiologia , Inflamação/psicologia , Mucosa Intestinal/fisiopatologia , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/psicologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Comorbidade , Feminino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Organochlorine pesticide lindane in the environment and biota results in the potential risks on ecosystem and human health. Lindane can adversely affect the locomotion and nervous system, yet the potential neurotoxicity of lindane over generations remains uncertain. In this study, the neurotoxicity and underlying mechanisms in Caenorhabditis elegans (C. elegans) were investigated after parental (P0) exposure to lindane at environmentally relevant concentrations over generations. Exposure to lindane at concentrations of 10-100 ng/L significantly decreased body bends and head thrashes in P0 generation. Significant decrease of fluorescence labeled different neurotransmitters, and clear morphological changes by exposure to lindane at 10-100 ng/L suggested that lindane could induce the neuronal damage in C. elegans. During the transgenerational process, decreased locomotive behaviors were also observed in F1-F3 generations, and head thrashes returned to normal levels in F4 generation. Moreover, lindane exposure down-regulated the expression of dat-1, dop-1, glr-1 and mod-1genes, while up-regulated unc-30 gene in P0 generation, which recovered to normal levels in F4 generation. Interestingly, eat-4 continued to be regulated from inhibition to stimulation in P0-F4 generations, suggesting that glutamatergic transmission may more contribute to the neurotoxicity of lindane over generations.
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Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Ecossistema , Hexaclorocicloexano/toxicidade , Humanos , LocomoçãoRESUMO
The critical role of transition metal dyshomeostasis in Alzheimer's disease (AD) pathology poses demands of in vivo imaging for brain copper levels. Nanostructured probes afford prolonged retention time, increased accumulation, and enhanced photostability; however, their development for activatable photoacoustic (PA) imaging remains largely unexplored. We develop a principle of concept for activable PA imaging using in situ cation exchange of ultrathin zinc selenide (ZnSe) nanoplatelets for monitoring brain copper levels in AD mice. We start from quantitative modeling of optical absorption, time-resolved temperature field, and thermal expansion of copper selenide (CuSe) nanocrystals of different morphologies and reveal that ultrathin nanoplatelets afford substantial enhancement of near-infrared (NIR) absorption and PA pressures as compared to nanodots and nanoparticles. By tethering with a blood-brain barrier (BBB)-targeting peptide ligand, the ultrathin ZnSe nanoplatelet probe efficiently transports across the BBB and rapidly exchanges with endogenous copper ions, boosting activatable PA imaging of brain copper levels. We also demonstrate that the efficient exchange of ZnSe nanoplatelets with copper ions can reduce oxidative stress of neurons and protect neuronal cells from apoptosis. The nanoplatelet probe provides a paradigm for activatable PA imaging of brain copper levels, highlighting its potential for pathophysiologic study of AD.
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Doença de Alzheimer , Técnicas Fotoacústicas , Animais , Camundongos , Cobre , Doença de Alzheimer/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Compostos de ZincoRESUMO
OBJECTIVE: To evaluate the effect of pronase on amoxicillin and metronidazole concentrations in gastric tissue. METHODS: C57BL/6 mice were randomly divided into experimental group (n = 70) and control group (n = 70). Amoxicillin (28.6 mg/kg), metronidazole (22.5 mg/kg) and omeprazole (138.2 mg/kg) were administered orally to C57BL/6 mice, combined with pronase (110 mg/kg) or same amount of sterile PBS. Gastric tissue and blood plasma samples were taken at 10 point-in-time (7 mice/time) from 15 min up to 360 min after administration. Concentrations of amoxicillin and metronidazole were detected by high performance liquid chromatography. Gastritis index of gastric mucosa (hematoxylin-eosin staining) and the gastric tissue expressions of mucin 5AC (Western blot) were detected at 120 min and 360 min after administration. RESULTS: The time to peak concentration of amoxicillin and metronidazole in gastric tissue appeared earlier than that in blood plasma (15 min vs 60 min). Tissue concentrations of amoxicillin and metronidazole of experimental group were significantly higher than those of control, and they were mainly at 15 min to 90 min (P < 0.05). Plasma concentrations of amoxicillin and metronidazole of experimental group at 15 min and 30 min were higher than those of control (P < 0.05). There was no difference in gastritis index between experimental group and control at 120 min and 360 min after administration (0.28 ± 0.18 vs 0.14 ± 0.14, P > 0.05; 0.43 ± 0.20 vs 0.28 ± 0.18, P > 0.05). The expressions of mucin 5AC in experimental group were lower than those of control (0.036 ± 0.006 vs 0.197 ± 0.058; P < 0.05; 0.039 ± 0.008 vs 0.208 ± 0.072, P < 0.05). CONCLUSIONS: Pronase can significantly enhance the drugs penetration from mucus into gastric tissue. Concentrations of amoxicillin and metronidazole of experimental group in local gastric tissue and plasma are higher than those of control, especially in improving concentrations of gastric tissue and prolongation of exposed time.
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Amoxicilina/administração & dosagem , Antiulcerosos/administração & dosagem , Mucosa Gástrica/química , Infecções por Helicobacter/tratamento farmacológico , Metronidazol/administração & dosagem , Pronase/administração & dosagem , Amoxicilina/uso terapêutico , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Gastrite/tratamento farmacológico , Helicobacter pylori , Metronidazol/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Pronase/uso terapêuticoRESUMO
The Bohai Sea has recently suffered several seasonal oxygen-deficiency, even hypoxia events during the summer. To better understand effects of dissolved oxygen (DO) concentration on the bacterial composition in particle attached (PA) and free living (FL) fractions during the transition from oxic water to low oxygen conditions, the bacterial communities under three different oxygen levels, i.e., high oxygen (HO, close to 100% O2 saturation), medium oxygen (MO, close to 75% O2 saturation), and low oxygen (LO, close to 50% O2 saturation) in the Bohai Sea were investigated using 16S rRNA amplicon sequencing. Fourteen water samples from 5 stations were collected during a cruise from August to September in 2018. The results showed that the sequences of Proteobacteria and Actinobacteriota jointly accounted for up to 74% across all 14 samples. The Shannon index in HO samples were significantly higher than in LO samples (P < 0.05), especially in PA communities. The composition of bacterial communities varied by oxygen concentration in all samples, and the effect was more pronounced in the PA fraction, which indicates that the PA fraction was more sensitive to the change in oxygen concentration, possibly due to the tighter interactions in this community than in the FL fraction. This study provides novel insights into the distribution of bacterial communities, and clues for understanding the responses of bacterial communities in the Bohai Sea during the transition from the oxic to oxygen-deficient zones.
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Bactérias , Água do Mar , Bactérias/genética , Humanos , Hipóxia , Oxigênio , Filogenia , RNA Ribossômico 16S/genéticaRESUMO
Aquatic products are an important source of environmental pollutants to humans. This study was conducted to assess the bioaccessibility of selected brominated flame retardants and heavy metals in common aquatic products from the Pearl River Delta, South China, as well as associated human health risks. Based on a questionnaire survey, ten of the most consumed aquatic products were collected from local markets. The bioaccessibility of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDDs), and heavy metals was assessed using an in vitro gastrointestinal model. Bioaccessibility of heavy metals (33.0-84.0%) and HBCDDs (38.5-68.4%) was significantly higher than that of PBDEs (13.4-65.4%). Total non-carcinogenic and carcinogenic risks from heavy metal consumption were much higher than the threshold values due to excessive abundances of arsenic in shellfish (HQâ¯=â¯2.45, CRâ¯=â¯1.1â¯×10-3). Furthermore, middle-aged populations and females were subjected to greater health risks due to different intakes of aquatic products among age and gender groups. Significant difference in bioaccessibility among analytes indicated that bioaccessibility of pollutants is non-negligible in health risk assessment. This is the first study systematically investigating health risks of aquatic products consumption and concludes that shellfish is a great cause for concern for the PRD residents.
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Retardadores de Chama , Hidrocarbonetos Bromados , Metais Pesados , China , Monitoramento Ambiental , Feminino , Retardadores de Chama/análise , Éteres Difenil Halogenados/análise , Éteres Difenil Halogenados/toxicidade , Humanos , Hidrocarbonetos Bromados/análise , Metais Pesados/análise , Pessoa de Meia-Idade , RiosRESUMO
OBJECTIVE: Collagenous gastritis is a rare entity, characterized by the deposition of a subepithelial collagen band with an inflammatory infiltrate in the mucosa. This report describes the first case of collagenous gastritis occurring in a young Chinese woman and reviews the literatures. METHODS: The patient underwent the gastroscopy screening, and the biopsy specimens were treated with HE staining, Masson staining, Congo red staining and Warthin-Starry staining.Patients' clinical data was discussed and followed up. RESULTS: A twenty-year-old girl had intermittent epigastric pain for 4 years, abdominal distention, hiccup and weight loss for two months. The gastric endoscopy revealed diffuse white nodular appearance of the mucosa in angular incisura and antrum. Pathologic examination of the gastric biopsies from the antrum and angular showed a subepithelial collagen deposition with moderate infiltrates of lymph plasma cells and eosinophils of the lamina propria. The collagen band measured up to 120.3 µm (mean 43.8 µm). Prednisone 20 mg/d for 4 weeks led to clinical remission and weight gain. CONCLUSION: There are about 40 cases in literatures to date, and the cause and pathogenesis of collagenous gastritis remain unknown. According to the clinical and pathological characteristics, the patient in this article is the subtype of collagenous gastritis that occurring in children and young adults. Specific therapy has not been established, the gluten-free diet and glucocorticosteroid may be helpful to relieve symptoms in collagenous gastritis patients.
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Mucosa Gástrica/patologia , Gastrite/patologia , Povo Asiático , Biópsia , Colágeno , Feminino , Gastroscopia , Humanos , Adulto JovemRESUMO
Developing highly efficient chemodynamic therapy (CDT)-based theranostic technology for cancer treatment is highly desired but still challenging. A novel nanotheranostic platform is constructed for enhanced CDT by engineering hybrid CaO2 and Fe3O4 nanoparticles with a hyaluronate acid (HA) stabilizer and NIR fluorophore label. This design not only enables the nanotheranostic agent to afford highly efficient CDT against tumor cells but also confers NIR fluorescence (NIRF) and magnetic resonance (MR) bimodal imaging for in vivo visualization of CDT. Moreover, the use of the HA stabilizer allows for the facile synthesis of the nanotheranostic agent with excellent biocompatibility and active targetability. The nanotheranaostic agent possesses a high capacity of self-supplying H2O2 and producing â¢OH in acidic conditions, while retaining the desired stability under physiological conditions. It also demonstrates high selectivity to tumor cells via CDT with minimized toxicity to normal cells. In vivo studies reveal that our nanotheranaostic agent exhibits efficacious tumor growth inhibition via a CDT mechanism with favorable biosafety. Moreover, in vivo visualization of the CDT progress via NIRF and MR bimodal imaging demonstrates specific targeting and treatment of tumors. The developed H2O2 self-supplying, active targeting, and bimodal imaging nanotheranostic platform holds the potential as a highly efficient strategy for CDT of cancer.
Assuntos
Compostos de Cálcio , Óxido Ferroso-Férrico , Peróxido de Hidrogênio/metabolismo , Nanopartículas , Neoplasias Experimentais/tratamento farmacológico , Óxidos , Fotoquimioterapia , Animais , Compostos de Cálcio/química , Compostos de Cálcio/farmacologia , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , Óxido Ferroso-Férrico/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Óxidos/química , Óxidos/farmacologia , Nanomedicina Teranóstica , Microambiente Tumoral/efeitos dos fármacosRESUMO
Lindane, a lipophilic pollutant, may be toxic to organisms. To explore the toxic effects of lindane and the underlying mechanisms of this toxicity, the animal model Caenorhabditis elegans (C. elegans) was exposed to lindane for 3 d at environmentally relevant concentrations (0.01-100 ng/L) and the physiological, biochemical, and molecular indices were evaluated. Subacute exposure to 10-100 ng/L of lindane caused adverse physiological effects on the development, reproduction, and locomotion behaviors in C. elegans. Exposure to 1-100 ng/L of lindane increased the accumulation of Nile red and blue food dye, which suggested high permeability of the intestine in nematodes. Lindane exposure also significantly influenced the expression of genes related to intestinal development (e.g., mtm-6 and opt-2). Moreover, reactive oxygen species production, lipofuscin accumulation, and expression of oxidation resistance genes (e.g., sod-5 and isp-1) were significantly increased in C. elegans exposed to 10-100 ng/L of lindane, which indicated that lindane exposure induced oxidative stress. According to Pearson correlation analyses, oxidative stress and intestinal damage were significantly correlated with the adverse physiological effects of lindane. Therefore, the adverse effects of lindane may have been induced by intestinal damage and oxidative stress, and mtm-6, opt-2, sod-5, isp-1, and mev-1 might play important roles in the toxicity of lindane.