A tumor-pH-responsive phthalocyanine as activatable type I photosensitizer for improved photodynamic immunotherapy.

The development of a simple drug formulation capable of achieving both activatable type I photoreaction and tumor-responsive release of immunomodulator is crucial for advancing photodynamic immunotherapy (PDIT). Herein, we present a nanostructured photosensitizer (NP5) that is activated by the acidic tumor microenvironment to produce type I reactive oxygen species (ROS) under light irradiation and release the immunomodulator demethylcantharidin (DMC) for PDIT. The NP5 is formed by self-assembly of a versatile phthalocyanine molecule which is composed of DMC and phthalocyanine linked via a pH-responsive amide bond.

Nrf2/Keap1 pathway in countering arsenic-induced oxidative stress in mice after chronic exposure at environmentally-relevant concentrations.

Contamination of drinking water by carcinogen arsenic (As) is of worldwide concern as its exposure poses potential threat to human health. As such, it is important to understand the mechanisms associated with As-induced toxicity to humans. The Nrf2/Keap1 signal pathway is one of the most important defense mechanisms in cells to counter oxidative stress; however, limited information is available regarding its role in countering As-induced stress in model animal mouse.

Environmentally relevant concentrations of arsenic induces apoptosis in the early life stage of zebrafish.

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 μg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 μg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h.

Ecotoxicological assessment of spent battery extract using zebrafish embryotoxicity test: A multi-biomarker approach.

Water environmental pollution caused by spent batteries is a nonignorable environmental issue. In this study, the early life stage of zebrafish was employed to assess the environmental risk of spent batteries after exposure to 0, 1%, 2%, 5% and 10% spent battery extract for 120 h. Our results clearly indicated that spent battery extract can significantly decrease the survival rate, hatching rate and body length and increase heart rate.

Antioxidant responses and pathological changes in the gill of zebrafish (Danio rerio) after chronic exposure to arsenite at its reference dose.

Gill, as the organ of fish to contact most directly with xenobiotics, suffered more threat. To evaluate the impact of arsenite (AsIII) on the gill of fish, we measured the antioxidative responses (superoxide dismutase (SOD) and catalase (CAT) activities) and oxidative damage (malondialdehyde (MDA) content), histological changes and mRNA transcriptional responses of zebrafish gill, after exposure to AsIII (0, 10, 50, 100, and 150 μg L) solutions for 28 days. We found that AsIII increased the activities of CAT by 46%-87%, decreased the activities of SOD and the contents of MDA by 19% and 21%-32%.

Lead bioavailability in different fractions of mining- and smelting-contaminated soils based on a sequential extraction and mouse kidney model.

Lead bioavailability in contaminated soils varies considerably depending on Pb speciation and sources of contamination. However, little information is available on bioavailability of Pb associated with different fractions. In this study, the Tessier sequential extraction was used to fractionate Pb in 3 contaminated soils to exchangeable (F1), carbonate-bound (F2), Fe/Mn oxides-bound (F3), organic-bound (F4), and residual fractions (F5).

Genetic polymorphisms, forensic efficiency and phylogenetic analysis of 17 autosomal STR loci in the Han population of Wuxi, Eastern China.

The autosomal short tandem repeat (STR) plays a unique role in population comparisons, phylogenetic reconstruction and migration history tracing. This study investigated the frequencies of 17 autosomal STR loci in the Han population from Wuxi, Eastern China, with the aim of expanding the available population information in human genetic databases and for forensic DNA analysis. The genetic polymorphisms of 17 STR loci were analysed in 5358 individuals of the Han population from Wuxi, Eastern China.

Environmentally relevant concentrations of arsenite induces developmental toxicity and oxidative responses in the early life stage of zebrafish.

Arsenic (As) present in water is a nonignorable environmental issue, even at low concentrations (≤150 μg L). To evaluate the toxic effect of low concentrations of As, zebrafish at early life stage were exposed to 0, 25, 50, 75, or 150 μg L AsIII for 120 h. Our results indicated that low concentration of AsIII decreased zebrafish larvae's survival rate to 85%, 89% and 86% at 50, 75 and 150 μg L.

Chronic exposure to dichloroacetamide induces biochemical and histopathological changes in the gills of zebrafish.

To evaluate the impact of DCAcAm on zebrafish gill, we measure the responses of antioxidant enzyme (superoxide dismutase, SOD), lipid peroxidation (malondialdehyde, MDA), ATPase (Na /K -ATPase and Ca /Mg -ATP) and histopathological changes of gill in adult zebrafish, after exposed to different concentrations of DCAcAm (0, 1, 10, 100, and 1000 μg L ) for 30 days. Results indicated that DCAcAm first increased and then decreased SOD activity, and DCAcAm also lowered the activities of Na /K -ATPase and Ca /Mg -ATPase. These results indicated that high affinity of DCAcAm probably be a main factor, which can damage the structures of enzymes, thereby inhibiting the SOD and ATPase activities.

The toxicity of 2,6-dichlorobenzoquinone on the early life stage of zebrafish: A survey on the endpoints at developmental toxicity, oxidative stress, genotoxicity and cytotoxicity.

2,6-dichlorobenzoquinone (2,6-DCBQ), an emerging disinfection by-production, frequently occurs in reclaimed water and drinking water. However, limited information was available regarding its toxicity. To evaluate its impact, zebrafish at early life stage were exposed to 0, 10, 30, 60, 90, or 120 μg L 2,6-BDCQ for 72 h.

Impact on growth, oxidative stress, and apoptosis-related gene transcription of zebrafish after exposure to low concentration of arsenite.

Low concentrations of arsenic (As) contamination in aquatic environment is a worldwide issue, which is of great concern. To evaluate the impact of low concentrations of As on zebrafish, we measured the growth, antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT), oxidative damage (malondialdehyde, MDA) and apoptosis-related genes (nrf2, p53 and c-jun) of adult zebrafish after exposing to different AsIII concentrations (0, 10, 50, 100 or 150 μg L) for 28 d. Results indicated that exposure to low AsIII concentrations decreased the zebrafish weight by 14%, increased the activities of SOD and CAT by 23-41% and 31-59%, decreased the contents of MDA by 29-54%, and modulated transcription of apoptosis related genes.

Thyrotoxicity of arsenate and arsenite on juvenile mice at organism, subcellular, and gene levels under low exposure.

Arsenic contamination in drinking water is a worldwide issue, posing threat to human health. Arsenic is an endocrine system disruptor, however, limited information is available regarding its long-term effects on thyroid endocrine system at low exposure. In this study, we assessed the thyroid toxicity of arsenate (AsV) and arsenite (AsIII) at 10-100 μg L in juvenile mice after 8-week of exposure via drinking water.

Effect of phosphate amendment on relative bioavailability and bioaccessibility of lead and arsenic in contaminated soils.

Hand-to-mouth activity is an important pathway for children's exposure to contaminated soils, which is often co-contaminated by Pb and As in mining and smelting sites. To reduce soil Pb risk to humans by oral exposure, phosphate amendments have been used to reduce Pb relative bioavailability (RBA), but its efficiency has not been investigated using validated in vitro assays nor its influence on As-RBA. Here, 5 contaminated soils (A-E) were amended with 0.

Effects of novel brominated flame retardant TBPH and its metabolite TBMEHP on human vascular endothelial cells: Implication for human health risks.

As a replacement for polybrominated diphenyl ethers, bis-(2-ethylhexyl) tetrabromophthalate (TBPH) is widely used as a novel flame retardant and has been detected in many environmental matrix including human blood. TBPH can be metabolized into mono-(2-ethyhexyl) tetrabromophthalate (TBMEHP) by carboxylesterase. However, their adverse effects on human vascular endothelium and their potential impacts on human cardiovascular disease are unknown.

Arsenic Relative Bioavailability in Rice Using a Mouse Arsenic Urinary Excretion Bioassay and Its Application to Assess Human Health Risk.

A steady-state mouse model was developed to determine arsenic (As) relative bioavailability (RBA) in rice to refine As exposure in humans. Fifty-five rice samples from 15 provinces of China were analyzed for total As, with 11 cooked for As speciation and bioavailability assessment. Arsenic concentrations were 38-335 μg kg, averaging 133 μg kg, with As being dominant (36-79%), followed by DMA (18-58%) and As (0.

Lead relative bioavailability in soils based on different endpoints of a mouse model.

Mouse is an acceptable animal model to measure lead (Pb) relative bioavailability (RBA) in contaminated soils; however, there is a lack of comparisons among Pb-RBA measurements based on different endpoints and dosing approaches. In this study, 12 soils (47.8-8123mg Pbkg) were assessed for Pb-RBA using Pb accumulation in mouse liver, kidneys, and/or femur following a 10-d steady state soil dose via diet, with 6 soils being measured using mouse bioassays with area under the mouse blood Pb concentration time curve (AUC) following a single gavaged dose as the endpoint.

Mechanisms of arsenic disruption on gonadal, adrenal and thyroid endocrine systems in humans: A review.

Due to its toxicity as a carcinogen and wide distribution in the environment, arsenic (As) exposure in humans is of public concern globally. Many studies have manifested that As exposure induces cancers besides pathological effects in humans. Animal studies showed that chronic As exposure induces serious neurological effects.

Assessment of cadmium bioaccessibility to predict its bioavailability in contaminated soils.

In vitro assays have been developed to determine metal bioaccessibility in contaminated soils; however, their application to Cd is limited. To assess their suitability to determine Cd relative bioavailability (RBA), Cd-RBA in 12 contaminated soils containing 3.00-296mgkg(-1) Cd were determined using a mouse model and compared with Cd bioaccessibility data based on four assays including the UBM, SBRC, IVG, and PBET.

Molecular mechanisms of dust-induced toxicity in human corneal epithelial cells: Water and organic extract of office and house dust.

Human corneal epithelial (HCE) cells are continually exposed to dust in the air, which may cause corneal epithelium damage. Both water and organic soluble contaminants in dust may contribute to cytotoxicity in HCE cells, however, the associated toxicity mechanisms are not fully elucidated. In this study, indoor dust from residential houses and commercial offices in Nanjing, China was collected and the effects of organic and water soluble fraction of dust on primary HCE cells were examined.

Mechanisms of housedust-induced toxicity in primary human corneal epithelial cells: Oxidative stress, proinflammatory response and mitochondrial dysfunction.

Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5-320μg/100μL for 24h.

Arsenic Relative Bioavailability in Contaminated Soils: Comparison of Animal Models, Dosing Schemes, and Biological End Points.

Different animals and biomarkers have been used to measure the relative bioavailability of arsenic (As-RBA) in contaminated soils. However, there is a lack of As-RBA comparison based on different animals (i.e.

Arsenic impacted the development, thyroid hormone and gene transcription of thyroid hormone receptors in bighead carp larvae (Hypophthalmichthys nobilis).

Arsenic (As) contamination in aquatic environment adversely impacts aquatic organisms. The present study assessed the toxicity of different As species and concentrations on bighead carp (Hypophthalmichthys nobilis) at early life stage, a major fish in Yangtze River, China. We measured the changes in embryo and larvae survival rate, larvae aberration, concentrations of thyroid hormone thyroxine, and transcription levels of thyroid hormone receptors (TRs) in fish larvae after exposing to arsenite (AsIII) or arsenate (AsV) at 0, 10, 30, 50, 100, or 150 μg L(-1) for 78 h.

Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h.

Interactive effects of mercury and arsenic on their uptake, speciation and toxicity in rice seedling.

Rice can take up and translocate more As and Hg than other cereal crops. A hydroponic experiment was conducted to investigate their interactive effects on their uptake and toxicity in rice seedling after exposing to As(III) (0.1, 0.

Assessment of immune cells and function of the residual spleen after subtotal splenectomy due to splenomegaly in cirrhotic patients.

Background: The spleen is thought to be central in regulating the immune system, a metabolic asset involved in endocrine function. Overwhelming postsplenectomy infection leads to a mortality rate of up to 50%. However, there is still controversy on performing subtotal splenectomy as treatment of splenomegaly due to portal hypertension in cirrhotic patients.