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1.
Article in English | MEDLINE | ID: mdl-38923573

ABSTRACT

BACKGROUND AND AIM: Lipid metabolism disorder is the primary feature of numerous refractory chronic diseases. Fatty acid oxidation, an essential aerobic biological process, is closely related to the progression of NAFLD. The forkhead transcription factor FOXO1 has been reported to play an important role in lipid metabolism. However, the molecular mechanism through which FOXO1 regulates fatty acid oxidation remains unclear. METHODS: Transcriptomic analysis was performed to examine the cellular expression profile to determine the functional role of FOXO1 in HepG2 cells with palmitic acid (PA)-induced lipid accumulation. FOXO1-binding motifs at the promoter region of aldehyde dehydrogenase 1 family member L2 (ALDH1L2) were predicted via bioinformatic analysis and confirmed via luciferase reporter assay. Overexpression of ALDH1L2 was induced to recover the impaired fatty acid oxidation in FOXO1-knockout cells. RESULTS: Knockout of FOXO1 aggravated lipid deposition in hepatic cells. Transcriptomic profiling revealed that knockout of FOXO1 increased the expression of genes associated with fatty acid synthesis but decreased the expression of carnitine palmitoyltransferase1a (CPT1α) and adipose triglyceride lipase (ATGL), which contribute to fatty acid oxidation. Mechanistically, FOXO1 was identified as a transcription factor of ALDH1L2. Knockout of FOXO1 significantly decreased the protein expression of ALDH1L2 and CPT1α in vitro and in vivo. Furthermore, overexpression of ALDH1L2 restored fatty acid oxidation in FOXO1-knockout cells. CONCLUSION: The findings of this study indicate that FOXO1 modulates fatty acid oxidation by targeting ALDH1L2.

2.
J Gastroenterol Hepatol ; 38(12): 2215-2227, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37839851

ABSTRACT

BACKGROUND AND AIMS: Mitochondrial dysfunction plays a crucial role in the progression of non-alcoholic steatohepatitis (NASH). Mitochondrial division inhibitor 1 (Mdivi1) is a potential inhibitor of dynamin-related protein (Drp1) and mitochondrial fission. However, the therapeutic effect of Mdivi1 against NASH and its underlying molecular mechanisms remain unclear. METHODS: In this study, we established mouse models of NASH by inducing high-fat/high-cholesterol (HFHC) or methionine- and choline-deficient (MCD) diets and treated the animals with 5 mg/kg/day Mdivi1 or placebo. RESULTS: Treatment with Mdivi1 significantly alleviated diet-induced fatty liver phenotypes, including increased liver weight/body weight ratio, insulin resistance, hepatic lipid accumulation, steatohepatitis, and liver injury. Furthermore, Mdivi1 treatment suppressed HFHC or MCD diet-induced changes in the expression of genes related to lipid metabolism and inflammatory cytokines. Additionally, Mdivi1 reduced macrophage infiltration in the injured liver and promoted polarization of macrophages towards the M1 phenotype. At the molecular level, Mdivi1 attenuated mitochondrial fission by reducing Drp1 activation and expression, thereby decreasing mitochondrial reactive oxygen species accumulation and mitochondrial DNA damage. Moreover, Mdivi1-treated mice exhibited elevated levels of phosphorylated-c-Jun N-terminal kinase (p-JNK), mitochondrial fission factor (MFF), cleaved caspase 3 protein, and TUNEL-positive cell expression in the liver, suggesting that Mdivi1 might ameliorate mitochondrial dysfunction and reduce hepatocyte apoptosis by inhibiting the JNK/MFF pathway. CONCLUSION: Collectively, Mdivi1 protected against diet-induced NASH by restoring mitochondrial homeostasis and function, potentially through its inhibitory effect on the JNK/MFF pathway. Consequently, further investigation of Mdivi1 as a promising drug for NASH treatment is warranted.


Subject(s)
Mitochondrial Diseases , Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/etiology , Non-alcoholic Fatty Liver Disease/metabolism , Liver/metabolism , Cytokines/metabolism , Mitochondria/metabolism , Transcription Factors/metabolism , Choline/metabolism , Dynamins , Mitochondrial Diseases/metabolism , Mice, Inbred C57BL , Methionine , Disease Models, Animal
3.
Discov Nano ; 18(1): 94, 2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37477789

ABSTRACT

Effective and safe delivery of small interfering RNA (siRNA) by nanomaterials to cancer cells is one of the main challenges in cancer treatment. In this study, we constructed the selenium nanoparticles conjugated with RGDfC (one tumor-targeted polypeptide) to prepare a biocompatible gene vector (RGDfC-SeNPs) and then loaded with siDCBLD2 to synthesize the RGDfC-Se@siDCBLD2 for colorectal cancer (CRC) therapy. As expected, RGDfC-SeNPs could enhance the cellular uptake of siDCBLD2 in human HCT-116 colon cancer cells by targeting polypeptide RGDfC on the surface of colon cancer cells. RGDfC-Se@siDCBLD2 could be effectively internalized by HCT-116 cells mainly through a clathrin-related endocytosis pathway. In addition, RGDfC-Se@siDCBLD2 exhibited high siRNA release efficiency in an acidic tumor environment. Moreover, RGDfC-Se@siDCBLD2 could inhibit the proliferation and induce apoptosis in HCT-116 cells by special silencing gene DCBLD2 expression. RGDfC-Se@siDCBLD2 could be specifically accumulated to the tumor sites and exhibited significantly anti-CRC efficacy on HCT-116 tumor-bearing mice without obvious side effects. Taken together, these results suggest that selenium nanoparticles can be used as an effective gene vector with good biocompatibility, and RGDfC-Se@siDCBLD2 provides a promising strategy for combining tumor-target and siRNA delivery in treating CRC.

4.
Environ Int ; 178: 108105, 2023 08.
Article in English | MEDLINE | ID: mdl-37517176

ABSTRACT

Cadmium (Cd) and polycyclic aromatic hydrocarbons (PAHs) are prominent soil contaminants found in industrial sites, and their combined effects on plants are not yet fully understood. To investigate the mechanisms underlying the co-exposure of Cd and PAHs and identify key biomarkers for their co-effects, an integrated analysis of metabolomics, transcriptomics, and proteomics was conducted on ryegrass leaves cultivated in soil. In nontarget metabolomics analysis, nine differentially expressed metabolites that were specifically induced by the compound exposure were identified. When combined with the analysis of differentially expressed genes and proteins, it was determined that the major pathways involved in the response to the co-stress of Cd and PAHs were linoleic acid metabolism and phenylpropanoid biosynthesis. The upregulation of 12,13-dihydroxy-9Z-octadecenoic acid and the downregulation of sinapyl alcohol were identified as typical biomarkers, respectively. Compared to scenarios of single exposures, the compound exposure to Cd and PAHs disrupted the oxidation of linoleic acid, leading to alterations in the profiles of linoleate metabolites. Additionally, it intensified hydroxylation, carboxylation, and methylation processes, and interfered with reactions involving coenzyme A, thus inhibiting lignin production. As a result, oxidative stress was elevated, and the cell wall defense system in ryegrass was weakened. The findings of this study highlight the ecological risks associated with unique biological responses in plants co-exposed to Cd and PAHs in polluted soils.


Subject(s)
Lolium , Polycyclic Aromatic Hydrocarbons , Soil Pollutants , Cadmium/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Lolium/metabolism , Linoleic Acid/metabolism , Linoleic Acid/pharmacology , Proteomics , Transcriptome , Biodegradation, Environmental , Soil , Metabolomics , Biomarkers/metabolism , Soil Pollutants/analysis
5.
Front Endocrinol (Lausanne) ; 14: 1145392, 2023.
Article in English | MEDLINE | ID: mdl-37020586

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and has become the leading chronic liver disease worldwide. NAFLD is viewed as the hepatic manifestation of metabolic syndrome, ranging from simple steatosis and nonalcoholic steatohepatitis (NASH) to advanced fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of NAFLD progression is still not clear. Pattern recognition receptor (PRR)-mediated innate immune responses play a critical role in the initiation of NAFLD and the progression of NAFLD-related HCC. Toll-like receptors (TLRs) and the cyclic GMP-AMP (cGAMP) synthase (cGAS) are the two major PRRs in hepatocytes and resident innate immune cells in the liver. Increasing evidence indicates that the overactivation of TLRs and the cGAS signaling pathways may contribute to the development of liver disorders, including NAFLD progression. However, induction of PRRs is critical for the release of type I interferons (IFN-I) and the maturation of dendritic cells (DCs), which prime systemic antitumor immunity in HCC therapy. In this review, we will summarize the emerging evidence regarding the molecular mechanisms of TLRs and cGAS in the development of NAFLD and HCC. The dysfunction of PRR-mediated innate immune response is a critical determinant of NAFLD pathology; targeting and selectively inhibiting TLRs and cGAS signaling provides therapeutic potential for treating NALF-associated diseases in humans.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , Carcinoma, Hepatocellular/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Liver Neoplasms/metabolism , Disease Progression , Fibrosis , Toll-Like Receptors
6.
Article in English | MEDLINE | ID: mdl-36833694

ABSTRACT

Commercial nano-scale carbon blacks (CB) are being harnessed widely and may impose potentially hazardous effects because of their unique properties, especially if they have been modified to grow reactive functional groups on their surface. Cytotoxicity of CB has been well studied but the membrane damage mechanisms and role of surface modification are still open to debate. Negatively and positively charged giant unilamellar vesicles (GUVs) were prepared using three lipids as model cell membranes to examine the mechanistic damage of CB and MCB (modified by acidic potassium permanganate) aggregates. Optical images showed that both anionic CB and MCB disrupted the positively charged but not the negatively charged GUVs. This disruption deteriorated with the rise and extension of exposure concentration and time. Lipids extraction caused by CBNs (CB and MCB together are called CBNs) was found. MCB caused more severe disruption than CB. MCB was enveloped into vesicles through an endocytosis-like process at 120 mg/L. MCB mediated the gelation of GUVs, perhaps through C-O-P bonding bridges. The lower hydrodynamic diameter and more negative charges may have been responsible for the distinction effect of MCB over CB. The adhesion and bonding of CBNs to the membrane were favored by electrostatic interaction and the practical application of CBNs warrants more attention.


Subject(s)
Nanoparticles , Phospholipids , Soot , Cell Membrane
7.
Article in English | MEDLINE | ID: mdl-36767236

ABSTRACT

Reducing the mobility and bioavailability of heavy metals in soils by adding exogenous materials is a technology for remediating soils contaminated with heavy metals. Unlike industrial sites, the use of such techniques in agricultural soils requires consideration of not only reducing the mobility of heavy metals but also avoiding adverse effects on soil fertility and the growth of plants. Due to the uncertainty of the stability of amendments applied to agricultural soil, the application of amendments in farmland soil is controversial. This article reviewed the field studies in which amendments were used to immobilize heavy metals, and identified the potential environmental impacts of all aspects of soil amendment usage, including production and processing, transportation, storage, application to soil, long-term stability, and plant absorption. Results of the study indicated that after identifying the environmental risks of the whole process of the application of improvers in agricultural fields, it is necessary to classify the risks according to their characteristics, and design differentiated risk control measures for the safe application of this type of technology.


Subject(s)
Environmental Restoration and Remediation , Metals, Heavy , Soil Pollutants , Soil , Soil Pollutants/analysis , Metals, Heavy/analysis , Plants , Biological Availability
8.
Article in English | MEDLINE | ID: mdl-36430016

ABSTRACT

Stabilization technology is widely used in the remediation of heavy metal-contaminated farmland soil. However, the evaluation method for the remediation effect is not satisfactory. To scientifically evaluate the remediation effect, this study constructed a comprehensive evaluation system by bibliometric analysis and an analytic hierarchy process (AHP). Ultimately, 16 indicators were selected from three aspects of the soil, crops, and amendment. The 16 indicators are divided into three groups, namely indicators I that can be evaluated according to the national standards of China, indicators II that can be evaluated according to the classification management of farmland and Indicators III that are the dynamic change indicators without an evaluation criterion. Comprehensive scores for 16 indicators were calculated using three response models, respectively. According to the difference between the scores before and after the remediation, the remediation effect is divided into five levels, which are excellent, good, qualified, poor, and very poor. This study provides a theoretical basis and insightful information for a farmland pollution remediation and a sustainable utilization.


Subject(s)
Environmental Restoration and Remediation , Metals, Heavy , Analytic Hierarchy Process , Environmental Pollution , Soil
10.
Front Oncol ; 12: 947284, 2022.
Article in English | MEDLINE | ID: mdl-36059693

ABSTRACT

Objective: This retrospective study compares the clinical results of cone beam CT (CBCT)-guided thermal ablation with those of helical tomotherapy in hepatocellular carcinoma (HCC) patients with pulmonary metastases. Methods: A total of 110 patients undergoing thermal ablation or helical tomotherapy for pulmonary metastases from April 2014 to December 2020 were included in the study. The endpoints were local tumor progression-free survival (LTPFS), overall survival (OS), and complications. Univariate and multivariate analyses using the Cox proportional hazard model were conducted to identify independent factors (univariate: P < 0.1; multivariate: P < 0.05). The Kaplan-Meier method was used to calculate the LTPFS and OS rates. Results: The results of 106 patients were taken into the final analysis. The 1- and 3-year LTPFS rates were 50 and 19% for the thermal ablation group and 65 and 25% for the helical tomotherapy group. The median LTPFS in the thermal ablation group was 12.1 months, while it was 18.8 months in the helical tomotherapy group (P = 0.25). The 1- and 3-year OS rates were 75 and 26% for the thermal ablation group and 77 and 37% for the helical tomotherapy group. The median OS was 18.0 months in the thermal ablation group and 23.4 months in the helical tomotherapy group (P = 0.38). The multivariate analyses found that α-fetoprotein (AFP) at <400 ng/ml (P = 0.003) was significantly associated with better LTPFS. Tumor number <3 and AFP <400 ng/ml were favorable prognostic factors for OS. There were no grades 3-5 adverse events in both groups. Grade 2 was recorded in three patients (4.8%) in the thermal ablation group and two patients (4.7%) in the helical tomotherapy group. Conclusions: For pulmonary metastases from HCC, CBCT-guided thermal ablation and helical tomotherapy provided comparable clinical effects and safety.

11.
Sci Total Environ ; 848: 157494, 2022 Nov 20.
Article in English | MEDLINE | ID: mdl-35914590

ABSTRACT

Highly oxygenated organic molecules (HOM) formed by the autoxidation of α-pinene initiated by OH radicals play an important role in new particle formation. It is believed that the accretion products, ROOR´, formed by the self- and cross-reaction of peroxy radicals (RO2 + R'O2 reactions), have extremely low volatility and are more likely to participate in nucleation. However, the mechanism of ROOR´ formation has not been fully demonstrated by experiment or theoretical calculation. Herein, we propose a novel mechanism of RO2 reacting with α-pinene (RO2 + α-pinene reactions) that have much lower potential barriers and larger rate constants than the reaction of RO2 with R'O2, which explains the ROOR´ formation found in the mass spectrometry experiments. The ROOR´ resulting from the reaction of RO2 with α-pinene can produce HOM dimers and trimers with a higher oxygen-to­carbon (O/C) ratio through a autoxidation chain. We also demonstrated that the presence of NOx and HO2 radical will reduce the RO2 concentration, but cannot completely inhibit the formation of HOM monomers and ROOR´. Even if one or both of RO2 radicals are acyl peroxy radicals (RC(O)O2), the potential barriers of the reactions between RC(O)O2 and α-pinene (RC(O)O2 + α-pinene reactions) are lower than that of RO2 reacting with RC(O)O2 (RO2 + RC(O)O2 reactions) or RC(O)O2 self-reactions (RC(O)O2 + RC(O)O2 reactions). The current work revealed, for the first time, a mechanism of RO2/RC(O)O2 reacting with α-pinene in the atmosphere, which provides new insight into the atmospheric chemistry of accretion products as SOA precursors.


Subject(s)
Atmosphere , Oxygen , Atmosphere/chemistry , Bicyclic Monoterpenes , Carbon , Oxygen/chemistry
12.
Sci Rep ; 12(1): 10562, 2022 06 22.
Article in English | MEDLINE | ID: mdl-35732673

ABSTRACT

Studying the pollution status, spatial distribution characteristics, and sources of heavy metals in farmland soil in Anxin County will provide a method basis for the next step of soil remediation. This study investigates the contents of Zn, Cu, Pb, Cd, and Ni in wheat grains and soil samples. Moreover, different methods are used to evaluate soil heavy metal pollution. The results show that the soil in the study area is weakly alkaline. Cu, Zn, and Ni contents in the ground are lower than the risk screening values for soil contamination of agricultural land. In comparison, Cd and Pb contents are higher than the screening value of soil pollution risk of agricultural land, and the proportion of points lower than the control value of soil pollution risk of agricultural land are 64.58% and 16.67%, respectively. The farmland with high Cd and Pb content is mainly distributed near roads and factories and concentrated primarily on 0-20 cm topsoil. The Cd content in wheat grains meets the standard, but 4.17% of the samples are close to 0.1 mg kg-1 (more than 0.09 mg kg-1). The Pb content of 50% of the wheat grain samples exceeds the lead limit in the standard. The evaluation results of the single factor pollution index and geoaccumulation index show that the pollution degree of heavy metals in the soil is Cd > Pb > Cu > Zn > Ni. The potential ecological risk index in the study area is 288.83, and the soil heavy metal pollution is at a moderate-considerable ecological risk level. The average value of Cd's single-factor environmental risk index is 233.51, which belongs to the high environmental risk and is the main influencing factor. Cd and Pb in soil are significantly disturbed by the production activities of heavy metal processing enterprises around the farmland. It is speculated that there are two primary sources of soil heavy metal pollution in the study area. Cd, Pb, Zn, and Cu are mainly industrial and mobile sources, and Ni is primarily agricultural and natural sources.


Subject(s)
Metals, Heavy , Soil Pollutants , Cadmium/analysis , China , Environmental Monitoring , Farms , Lead/analysis , Metallurgy , Metals, Heavy/analysis , Risk Assessment , Soil , Soil Pollutants/analysis
13.
Environ Res ; 198: 111198, 2021 07.
Article in English | MEDLINE | ID: mdl-33933486

ABSTRACT

Rice consumption is a major dietary source of human exposure to arsenic (As), with As bioavailability being an important factor influencing its health risk. In this study, the As bioaccessibility was measured in 11 rice grains (140-335 µg As kg-1), which were compared to As relative bioavailability previously measured based on a mouse bioassay (Li et al., 2017). Using modified physiologically-based extraction test for rice (MPBET), As bioaccessibility in raw rice samples (44-88% in the gastric phase and 47-102% in the intestinal phase) was similar to those in cooked rice (42-73% and 43-99%). Arsenic bioaccessibility in rice was generally higher in the intestinal phase than in the gastric phase, with Fe and Ca concentrations in rice being negatively correlated with As bioaccessibility in the gastric phase (R2 = 0.47-0.49). In addition, for cooked rice, strong positive correlation was observed between bioaccessible As and inorganic As (R2 = 0.63-0.72), suggesting inorganic As in rice was easier to dissolve than organic As in gastrointestinal digestive fluids. Due to limited variation in As bioaccessibility and As bioavailability among the 11 samples, a weak correlation was observed between them (R2 = 0.01-0.03); however, As bioaccessibility values measured by the gastric phase (GP) of the MPBET agreed with As bioavailability values based on a mouse bioassay, suggesting the potential of the MPBETGP to predict As bioavailability in rice. Future work is needed to ascertain the robustness of the MPBETGP in predicting As bioavailability in rice using additional samples.


Subject(s)
Arsenic , Oryza , Soil Pollutants , Arsenic/analysis , Biological Availability , Cooking , Minerals
14.
Sci Total Environ ; 780: 146422, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-33770596

ABSTRACT

In recent years, highly oxygenated organic molecules (HOMs) derived from photochemical reactions of α-pinene, the most abundant monoterpene, have been considered as important precursors of biogenic particles. However, the specific reactions of HOMs remain largely unknown, especially the corresponding formation and nucleation mechanism in the nanoscale. In this study, we implemented quantum chemical calculations and molecular dynamics (MD) simulations to explore the mechanism of the formation of HOM monomers/dimers by ozonolysis and autoxidation of α-pinene. Furthermore, we investigated the mechanisms of HOMs with different oxygen-to­carbon (O/C) ratios and functional groups participating in neutral and ion-induced nucleation. The results show that the formation of HOMs is hardly affected by water, sulfuric acid and ions. In the ion-induced nucleation, HOM can dominate the initial nucleation steps; however, in the neutral nucleation, HOMs are more likely to participate in the growth stage. In addition, the nucleation ability of HOM has a bearing on the O/C ratio and the types of the functional groups. The current calculations provide valuable insight into the formation mechanism of the pure organic particles at low sulfuric acid concentrations.

15.
Brachytherapy ; 20(2): 446-453, 2021.
Article in English | MEDLINE | ID: mdl-33309002

ABSTRACT

PURPOSE: The purpose of this study was to assess the efficacy of an iodine-125 (125I) seed strand combined with a metal stent compared with a metal stent for treatment of obstructive jaundice caused by pancreatic ductal adenocarcinoma (PDAC). METHODS AND MATERIALS: A retrospective analysis was carried out of patients who were referred to Shanghai Zhongshan Hospital of Fudan University with a diagnosis of PDAC between January 1, 2010 and January 31, 2019. A total of 110 consecutive patients with obstructive jaundice caused by PDAC were divided into the iodine-125 seed strand combined with a metal stent group (Group A = 48) and the metal stent group (Group B = 62). The primary outcome was stent obstruction-free survival time, and secondary outcomes were overall survival and complications. RESULTS: The median stent obstruction-free survival time was 133.0 (95% confidence interval (CI): 166.093-149.907) days, and the median overall survival was 212.0 (95% CI: 187.183-236.817) days in all patients. Median stent obstruction-free survival time was 175 days (95% CI 103.165-246.835 days) in Group A versus 120 days (95% CI 87.475-152.525 days) in Group B (p = 0.035). A lower Eastern Cooperative Oncology Group (ECOG) score (p = 0. 000) and iodine-125 seed strand combined with metal stent implantation (p = 0.008) were associated with a longer stent obstruction-free survival time. Obstruction length (p = 0.083), ECOG score (p = 0.000), and iodine-125 seeds (p = 0.037) might have potential impact on stent obstruction-free survival time and were included for multivariable analysis using the Cox proportional hazards model. Stent restenosis was observed in 18.8% (9/48) of patients in Group A and 54.8% (34/62) in Group B, respectively. There was no significant difference in median survival between Group A and Group B (p = 0.409). The median survival in Group A was 209 days (95% CI 150.750-267.250) and 202 days (95% CI 190.624-233.376) in Group B. The median survival of patients with a lower ECOG score was better than that of patients with a higher ECOG score (267 days vs 132 days, p = 0.000). The Grade 3 or 4 complications occurred in 4 (8.3%) of the 48 patients in Group A (one case of hemobilia, one case of liver abscess, two cases of choleperitonitis) and in 5 (8.1%) of the 62 patients in Group B (one case of hemobilia, two cases of liver abscess, two cases of choleperitonitis) (p = 0.972). CONCLUSIONS: Implantation of an iodine-125 seed strand combined with a metal stent provides longer obstruction-free survival time compared with a metal stent in patients with obstructive jaundice caused by PDAC. It seems reasonable to choose an iodine-125 seed strand combined with a metal stent as a treatment for these patients.


Subject(s)
Brachytherapy , Carcinoma, Pancreatic Ductal , Jaundice, Obstructive , Pancreatic Neoplasms , Brachytherapy/methods , Carcinoma, Pancreatic Ductal/complications , Carcinoma, Pancreatic Ductal/radiotherapy , China/epidemiology , Humans , Iodine Radioisotopes , Jaundice, Obstructive/etiology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/radiotherapy , Retrospective Studies , Stents , Treatment Outcome
16.
Ann Surg ; 273(6): 1066-1075, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33214446

ABSTRACT

OBJECTIVE: To evaluate the effects of the addition of preoperative hepatic and regional arterial chemotherapy (PHRAC) on prognosis of stage II and III colorectal cancer (CRC) in a multicenter setting. SUMMARY OF BACKGROUND DATA: Our previous single-center pilot trial suggested that PHRAC in combination with surgical resection could reduce the occurrence of liver metastasis (LM) and improve survival in CRC patients. METHODS: A prospective multi-center randomized controlled trial was conducted from December 2008 to December 2012 at 5 hospitals in China. Eligible patients with clinical stage II or III CRC who underwent curative resection were randomized to receive PHRAC plus adjuvant therapy (PHRAC arm) or adjuvant therapy alone (control arm). The primary endpoint was DFS. Secondary endpoints were cumulative LM rates, overall survival (OS), and safety (NCT00643877). RESULTS: A total of 688 patients from 5 centers in China were randomly assigned (1:1) to each arm. The five-year DFS rate was 77% in the PHRAC arm and 65% in the control arm (HR = 0.61, 95% CI 0.46-0.81; P = 0.001). The 5-year LM rates were 7% and 16% in the PHRAC and control arms, respectively (HR = 0.37, 95% CI 0.22-0.63; P < 0.001). The 5-year OS rate was 84% in the PHRAC arm and 76% in the control arm (HR = 0.61, 95% CI 0.43-0.86; P = 0.005). There were no significant differences regarding treatment related morbidity or mortality between the two arms. CONCLUSIONS: The addition of PHRAC could improve DFS in patients with stage II and III CRC. It reduced the incidence of LM and improved OS without compromising patient safety. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00643877.


Subject(s)
Antineoplastic Agents/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/surgery , Adult , Aged , Colorectal Neoplasms/pathology , Combined Modality Therapy , Female , Hepatic Artery , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Staging , Prognosis , Prospective Studies , Young Adult
17.
J Hazard Mater ; 398: 122815, 2020 11 05.
Article in English | MEDLINE | ID: mdl-32768857

ABSTRACT

Little is known about the potential threats of functionalized nano-carbon black (FNCB) combined with cadmium (Cd) to soil invertebrates. In this study, immunocompetent coelomocytes from Eisenia fetida are harnessed, and the joint cytotoxicity types of FNCB and Cd co-exposure are analyzed. The extracellular interaction mechanisms of FNCB and Cd were completely explored using adsorption kinetics and thermodynamics accompanied by isotherm batch experiments and Fourier infrared spectroscopy. The results indicated that functional amorphous carbon nanoparticles up to certain dose may injure cells due to their surface oxygen-containing groups. The MIXTOX model and the combination index suggested that the combined action of FNCB and Cd exhibited antagonism at the low dose/effect-level and synergism at the high dose/effect-level. FNCB decreased the intracellular free Cd2+ content at a low mixture dose, while it increased it at a high mixture dose. The adsorption of Cd on FNCB followed pseudo-second-kinetics and the Langmuir isotherm, hence better indicating a chemisorption, which was also supported by the activation energy (Ea = 36.6 kJ/mol), enthalpy change (ΔH = -98.4 kJ/mol), and functional group changes. Coordination binding should be responsible for the subsequent interaction of toxicity.


Subject(s)
Oligochaeta , Adsorption , Animals , Cadmium/toxicity , Kinetics , Soot/toxicity , Thermodynamics
18.
Environ Sci Pollut Res Int ; 27(15): 18423-18433, 2020 May.
Article in English | MEDLINE | ID: mdl-32185740

ABSTRACT

Previous researches have confirmed that modified nanoscale carbon black (MCB) can decrease the bioavailability of heavy metals in soil and accumulation in plant tissues, resulting in the increase of biomass of plant. However, as a nanoparticle, the effects of MCB on plant cell morphology and microbial communities in Cd-contaminated soil are poorly understood. This study, through greenhouse experiments, investigated the effects of MCB as an amendment for 5 mg·kg-1 Cd-contaminated soil on plant growth, plant cellular morphogenesis, and microbial communities. Two types of plants, metal-tolerant plant ryegrass (Lolium multiflorum), and hyperaccumulator plant chard (Beta vulgaris L. var. cicla) were selected. The results indicated that adding MCB to Cd-contaminated soil, the dry biomass of shoot ryegrass and chard increased by 1.07 and 1.05 times, respectively, comparing with control group (the treatment without MCB). Meanwhile, the physiological characteristics of plant root denoted that adding MCB reduced the damage caused by Cd to plants. The acid phosphatase activity of soils treated with MBC was higher and the dehydrogenase activity was lower than control group during whole 50 days of incubation, while the urease and catalase activity of soils treated with MBC were higher than control group after 25 days of incubation. When compared with the treatment without MCB, the abundances of nitrogen-functional bacteria (Rhodospirillum and Nitrospira) and phosphorus-functional bacteria (Bradyrhizobium and Flavobacterium) increased but that of nitrogen-functional bacteria, Nitrososphaera, declined. The presence of MCB resulted in increased microbial community abundance by reducing the bioavailability of heavy metals in soil, while increasing the abundance of plants by increasing the amount of available nitrogen in soil. The result of this study suggests that MCB could be applied to the in-situ immobilization of heavy metal in contaminated soils because of its beneficial effects on plants growth, root cellular morphogenesis, and microbial community.


Subject(s)
Microbiota , Soil Pollutants/analysis , Biodegradation, Environmental , Biomass , Cadmium/analysis , Morphogenesis , Plant Roots/chemistry , Soil , Soot
19.
Bull Environ Contam Toxicol ; 104(4): 477-483, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32193572

ABSTRACT

The application of nano-level passivating agents in the remediation of soil heavy metal pollution has received widespread attention, but its harm to soil animals should also be addressed. This study explored the effect of three nanomaterials-nanohydroxyapatite apatite (n-HAP), nano zeolite (n-zeolite), and nanometer iron oxide (n-Fe3O4), on catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content through filter paper contact test. The effects of nanomaterials spiked at 1.5%wt of soils on earthworm avoidance behavior were also be studied, and the crystallinity and surface charge of three nanomaterials were characterized. The results showed that the activities of CAT, SOD and POD and the content of MDA have been changed at different level. And earthworms have obvious avoidance behavior to the three kinds of nanomaterials. Therefore, nanomaterials do have adverse effects on earthworms, and their biological toxicity should be considered when selecting passivating agents for soil heavy metal pollution remediation.


Subject(s)
Avoidance Learning/drug effects , Environmental Restoration and Remediation/methods , Escape Reaction/drug effects , Nanostructures/toxicity , Oligochaeta/drug effects , Soil Pollutants/toxicity , Soil/chemistry , Animals , Catalase/metabolism , Malondialdehyde/metabolism , Nanostructures/chemistry , Oligochaeta/metabolism , Peroxidase/metabolism , Soil Pollutants/chemistry , Superoxide Dismutase/metabolism
20.
J Cancer Res Ther ; 15(4): 766-772, 2019.
Article in English | MEDLINE | ID: mdl-31436230

ABSTRACT

BACKGROUND/AIM: Percutaneous thermal ablation combined with transarterial chemoembolization (TACE) becomes a treatment option for unresectable hepatocellular carcinoma (HCC). This study aims to investigate the safety and feasibility of percutaneous thermal ablation combined with simultaneous TACE for patients with HCC ≤ 5 cm. MATERIALS AND METHODS: From June 2010 to February 2017, a total of 280 patients with HCC ≤ 5 cm who underwent percutaneous thermal ablation combined with simultaneous TACE were included in our study. Their clinical data were collected and analyzed. RESULTS: Major complications occurred in five cases (1.8%). The complete necrosis rate was 91.9%. The median overall survival (OS) was 66.5 months (95% confidence interval [CI] = 57.7-75.2). The OS rates in 1-, 3-, 5-, and 7-year were 96.7%, 76.0%, 59.7%, and 31.1%, respectively. Tumor size (hazard ratio = 1.826; 95% CI = 1.131-2.947; P = 0.014) was considered as independent prognostic factors of long-term survival. CONCLUSION: Percutaneous thermal ablation combined with simultaneous TACE is a safe and effective treatment for HCC ≤ 5 cm.


Subject(s)
Carcinoma, Hepatocellular/therapy , Catheter Ablation/mortality , Chemoembolization, Therapeutic/mortality , Hyperthermia, Induced/mortality , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Survival Rate , Treatment Outcome
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