Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Cu-Doped black phosphorus quantum dots as multifunctional Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal chemodynamic cancer therapy.

Chemodynamic therapy (CDT) is a cancer treatment that converts endogenous H2O2 into hydroxyl radicals (˙OH) through Fenton reaction to destroy cancer cells. However, there are still some challenges in accelerating the Fenton reaction of CDT and improving the biodegradability of nanocatalysts. Herein, a multifunctional biomimetic BPQDs-Cu@GOD (BCG) Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal CDT of cancer is reported. Cu2+ in BCG can be reduced to Cu+ by black phosphorus quantum dots (BPQDs), triggering a Cu+-mediated Fenton-like reaction to degrade H2O2 and generate abundant ˙OH for cancer CDT. The loaded glucose oxidase (GOD) can consume the glucose in the tumor to produce abundant H2O2 for Fenton-like reaction. In addition, Cu2+ in BCG can react with GSH in tumor cells to alleviate the antioxidant capacity of tumor tissues, further improving the CDT efficacy. Furthermore, the photothermal performance of BPQDs can be enhanced by capturing Cu2+, improving the photoacoustic imaging and photothermal therapy (PTT) functions. More importantly, the enhanced photothermal performance can rapidly accelerate the Fenton-like reaction under NIR irradiation. Finally, Cu2+ can accelerate the degradation of BPQDs, which can reduce the retention of reagents. As a novel multifunctional biocompatible Fenton nanocatalyst, BCG have great potential in cancer therapy.

Chiral Cu2-xSe Nanoparticles for Enhanced Synergistic Cancer Chemodynamic/Photothermal Therapy in the Second Near-Infrared Biowindow.

Chiral nanomaterials have great potential in improving the clinical therapeutic effect due to the unique chiral selectivity of biosystems. However, such a promising therapeutic strategy has so far received little attention in cancer treatment. Here, we report a first chiral Fenton catalyst, d-/l-penicillamine-modified Cu2-xSe nanoparticles (d-/l-NPs), for enhanced synergistic cancer chemodynamic therapy (CDT) and photothermal therapy (PTT) under the second near-infrared (NIR-II) light irradiation. The chiral effect study of chiral Cu2-xSe NPs on cancer cells shows that d-NPs exhibit stronger CDT-induced cytotoxicity than l -NPs due to the stronger internalization ability. Moreover, the hydroxyl radicals (•OH) produced in d-NP-treated cancer cells via the CDT effect can be further improved by NIR-II light irradiation, thereby increasing the apoptosis of cancer cells. In vivo experiments show that, compared with l-NPs, d-NPs exhibit a stronger photothermal effect on the tumor site under NIR-II light irradiation and could completely eliminate the tumor under the synergistic effect of CDT and PTT. This work shows that the chirality of the surface ligand of the nanomaterials could significantly affect their cancer curative effect, which opens up a new way for the development of anticancer nanomedicine.

The anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on acrylamide-induced neurotoxicity in rats.

BACKGROUND: Acrylamide (ACR) formed during heating of tobacco and carbohydrate-rich food as well as widely applied in industries has been known as a well-established neurotoxic pollutant. Although the precise mechanism is unclear, enhanced apoptosis, oxidative stress and inflammation have been demonstrated to contribute to the ACR-induced neurotoxicity. In this study, we assessed the possible anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin, the most active component in a popular spice known as turmeric, on the neurotoxicity caused by ACR in rats. METHODS: Curcumin at the dose of 50 and 100 mg/kg was orally given to ACR- intoxicated Sprague-Dawley rats exposed by ACR at 40 mg/kg for 4 weeks. All rats were subjected to behavioral analysis. The HE staining and terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (TUNEL) staining were used to detect histopathological changes and apoptotic cells, respectively. The mRNA and protein expressions of apoptosis-related molecule telomerase reverse transcriptase (TERT) were detected using real-time PCR and immunohistochemistry, respectively. The contents of malondialdehyde (MDA) and glutathione (GSH) as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured as the indicators for evaluating the level of oxidative stress in brain. The levels of pro-inflammatory cytokinestumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in the cerebral homogenates were detected using ELISA assay. RESULTS: ACR-induced weigh loss, deficits in motor function as well as pathological alterations in brains were significantly improved in rats administrated with 50 and 100 mg/kg curcumin. TUNEL-positive apoptotic cells in curcumin-treated ACR intoxicated brains were less than those in the ACR model group. Curcumin administration especially at the dose of 100 mg/kg upregulated the TERT mRNA expression and enhanced the number of TERT-positive cells in ACR-intoxicated cortex tissues. Moreover, curcumin treatment reduced the concentrations of TNF-α, IL-1ß and MDA, while increased the GSH contents as well as the SOD and GSH-Px activities in the cerebral homogenates, in comparison to ACR control group. CONCLUSIONS: These data suggested the anti-apoptotic, antioxidant and anti-inflammatory effects of curcumin on ACR-induced neurotoxicity in rats. Maintaining TERT-related anti-apoptotic function might be one mechanism underlying the protective effect of curcumin on ACR-intoxicated brains.

Protective effect of ethyl acetate fraction from Semen sojae germinatum, the processed sprout of Chinese black soybean, on rat experimental osteoarthritis.

BACKGROUND: Our previous in vitro study reported that the ethyl acetate fraction (EAF) of Semen sojae germinatum (SSG), the processed sprout of Chinese black soybean, possessed the potent anti-inflammatory and chondroprotective properties. The aim of the present work was to verify the in vivo antiosteoarthritic effect of EAF from SSG on a rat osteoarthritis (OA) model . METHODS: A classical rat OA model was surgically induced by anterior cruciate ligament transaction (ACLT). The OA rats were intra-articularly administered EAF from SSG for 8 weeks. The cartilage and synovial tissues were stained with hematoxylin and eosin (HE) to observe the histopathological changes. Safranin O/fast green staining was used to assess the glycosaminoglycan content in cartilage tissue sections. The expression of type II collagen and matrix metalloproteinase (MMP)-13 in cartilage was measured by immunohistochemistry. The apoptotic chondrocytes in the cartilage sections were detected using TUNEL assay. The concentrations of interleukin (IL)-1ß and tumor necrosis factor (TNF)-ɑ in synovial fluid were determined using ELISA. RESULTS: Intra-articular administration of EAF from SSG well retained the structure and superficial layer of cartilage tissues, ameliorated cartilage lesion and the degradation of cartilage matrix, including proteoglycan and type II collagen, induced by ACLT operation. The ACLT-induced upregulation of MMP-13 expression in the cartilage tissues was resisted by EAF from SSG. Moreover, EAF from SSG inhibited the ACLT-induced chondrocyte apoptosis. Compared to OA model group, the inflammatory status of synovial membrane was improved, the levels of inflammatory cytokines IL-1ß and TNF-ɑ in synovial fluid were decreased in rats administrated with EAF from SSG. CONCLUSION: These data suggested that EAF from SSG displayed in vivo protective effect on OA development via preventing the degeneration of articular cartilage, inhibiting chondrocyte apoptosis and suppressing synovial inflammation.

[Study on the correlation of serum folate and red blood cell folate level with birth defects and unexplained recurrent pregnancy loss].

OBJECTIVE: To understand the correlation of lower serum folate, and red blood cell (RBC) folate level with birth defects including unexplained recurrent pregnancy loss, and to evaluate the role of RBC folate level as a suitable marker for folate supplement. METHODS: Two hundred and ninety-nine non-pregnant women at child-bearing age with a birth defect history were selected as birth defect group. The levels of serum and RBC folate, and serum vitamin B(12) were determined. By comparing with the group of non-pregnant women at child-bearing age without any birth defect history (control group), we evaluated the correlation between lower serum folate, RBC folate level and main kinds of birth defects including unexplained recurrent pregnancy loss. And the levels of serum and RBC folate of birth defect group were also determined and compared before and after oral folate intake (5 mg/d) for one month. RESULTS: The serum folate level of birth defect group was not different from the control group (17 - 26 vs 14 nmol/L, P > 0.05). The RBC folate level of birth defect group except the urinary defect was significantly lower compared with the control group (233 - 547 vs 689 nmol/L, P < 0.05). After the oral folate intake (5 mg/d), the serum folate level of unexplained recurrent pregnancy loss group and neural tube defects group were significantly increased than before [(22 +/- 9) vs (27 +/- 12) nmol/L, (19 +/- 10) vs (25 +/- 18) nmol/L; P < 0.05]. The RBC folate level of unexplained recurrent pregnancy loss group and congenital heart defect group were significantly increased than before [(374 +/- 275) vs (567 +/- 397) nmol/L, (322 +/- 205) vs (527 +/- 351) nmol/L, P < 0.05]. CONCLUSION: RBC folate level is more closely correlated than serum folate level with the incidence of main birth defect.

[Correlation studies of contents of copper and organic components in Astragalus roots].

OBJECTIVE: To study the relationship between copper and organic components, total flavonoids of Astragalus (TFA), total saponins of Astragalus (TSA) and total polysaccharide of Astragalus (TPA). METHOD: TFA, TSA and TPA were extracted from Astragalus roots using different organic solvents, and determined by colorimetry. The concentration of copper in extracts was determined by graphite furnace atomic absorption spectrometry (GFAAS). RESULT: Copper was found in TFA, TPA and TSA, and its concentration in TFA and TPA was higher; the content of copper was correlated significantly to that of TFA and TPA (r1(2) = 0.754 8, F1 = 57.202, P < 0.01 and r2(2) = 0.499, F2 = 21.906, P < 0.01), while not to that of TSA ( r3(2) = 0.0026, F3 = 0.041, P > 0.1). CONCLUSION: Correlation analysis could reveal the relationship of copper with organic components in Astragalus roots; contents and structure characteristics of organic components might be important factors influencing the distribution of copper in Astragalus roots.