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1.
Environ Pollut ; 351: 124061, 2024 Apr 26.
Article En | MEDLINE | ID: mdl-38679131

Diffusive gradients in thin films technique (DGT) is recognized as a more reliable method for determining labile heavy metal (HM) concentration in soil than traditional destructive methods. However, the current DGT measurement index, CDGT, theoretically underestimates the true labile concentration (Clabile) of HMs in soil and lacks direct comparability with the conventional soil HM content indices due to unit differences. Here, we proposed CDGT-W, a new simple index which is defined as the HM accumulation in the binding layer, normalized to the weight of soil (optimized water content = 100% of the maximum water holding capacity) filled in the open cavity-type DGT device over a specified deployment time (optimized time = 24 h). The procedure for measuring CDGT-W is analogous to that of CDGT but includes precise determination of water content (water/dry soil) and the mass of soil filled in the cavity. We conducted measurements of Cu, Pb, Cr(Ⅵ) and As(V) as CDGT-W, CDGT, solution concentration (Csoln), and CaCl2 extractable concentration (CCaCl2) on three soils with a diverse range of HM concentrations. CDGT-W showed significant linear correlations with all other tested indexes. The ratios of CDGT-W to CCaCl2 varied between 0.30 and 0.98 for all HM-soil combinations with only one exception, a range much greater than CDGT/Csoln (typically <0.1) but lower than 1. This suggested that CDGT-W may more accurately reflect Clabile than CDGT (theoretically underestimates Cliable) and CCaCl2(likely overestimates Cliable). Additionally, CDGT-W measurements for these four HMs exhibited a broad measure concentration range and a low detection limit (mg/kg level). Consequently, CDGT-W may offer a more reliable alternative to CDGT for characterizing Clabile in unsaturated soils.

2.
Environ Sci Pollut Res Int ; 31(21): 30399-30414, 2024 May.
Article En | MEDLINE | ID: mdl-38607481

The rapid increase in soil acidity coupled with the deleterious effects of cadmium (Cd) toxicity had led to a decline in worldwide agricultural production. Rice absorbs and accumulates Cd(II) from polluted paddy soils, increasing human health risks throughout the food chain. A 35-day hydroponic experiment with four japonica and four indica (two each of them tolerant and sensitive cultivars) was conducted in this study to investigate the adsorption and absorption of Cd(II) by rice roots as related with surface chemical properties of the roots. The results showed that the three chemical forms of exchangeable, complexed, and precipitated Cd(II) increased with the increase in Cd(II) concentration for all rice cultivars. The roots of indica rice cultivars carried more negative charges and had greater functional groups and thus adsorbed more exchangeable and complexed Cd(II) than those of japonica rice cultivars. This led to more absorption of Cd(II) by the roots and greater toxicity of Cd(II) to the roots of indica rice cultivars and more inhibition of Cd(II) stress on the growth of the roots and whole plants of indica rice cultivars compared with japonica rice cultivars, which was one of the main reasons for more declines in the biomass and length of indica rice roots and shoots than japonica rice cultivars. Cd(II) stress showed more toxicity to the sensitive rice cultivars and thus greater inhibition on the growth of the cultivars due to more exchangeable and complexed Cd(II) adsorbed by their roots induced by more negative charges and functional groups on the roots compared with tolerant rice cultivar for both indica and japonica, which resulted in greater decreases in the biomass and length of roots and shoots as well as chlorophyll contents of the sensitive cultivars than the tolerant cultivars. The roots of sensitive rice cultivars also absorbed more Cd(II) than tolerant rice cultivars due to the same reasons as above. These findings will provide useful references for the safe utilization and health risk prevention of Cd-contaminated paddy fields.


Cadmium , Oryza , Plant Roots , Soil Pollutants , Oryza/metabolism , Cadmium/metabolism , Cadmium/toxicity , Plant Roots/metabolism , Soil Pollutants/metabolism , Soil Pollutants/toxicity , Adsorption , Soil/chemistry
3.
Article En | MEDLINE | ID: mdl-38326979

BACKGROUND AND AIM: The study aims to evaluate the feasibility of body mass index (BMI)-based individualized small bowel preparation for computed tomography enterography (CTE). METHODS: In this prospective randomized controlled study, patients undergoing CTE were randomly assigned to the individualized group or standardized group. Those in individualized group were given different volumes of mannitol solution based on BMI (1000 mL for patients with BMI < 18.5 kg/m2 , 1500 mL for patients with 18.5 kg/m2  ≤ BMI < 25 kg/m2 and 2000 mL for patients with BMI ≥ 25 kg/m2 ) while patients in the standardized group were all asked to consume 1500-mL mannitol solution. CTE images were reviewed by two experienced radiologists blindly. Each segment of the small bowel was assessed for small bowel image quality and disease detection rates. Patients were invited to record a diary regarding adverse events and acceptance. RESULTS: A total of 203 patients were enrolled and randomly divided into two groups. For patients with BMI < 18.5 kg/m2 , 1000-mL mannitol solution permitted a significantly lower rate of flatulence (P = 0.045) and defecating frequency (P = 0.011) as well as higher acceptance score (P = 0.015), but did not affect bowel image quality and diseases detection compared with conventional dosage. For patients with BMI ≥ 25 kg/m2 , 2000-mL mannitol solution provided better overall image quality (P = 0.033) but comparable rates of adverse events and patients' acceptance compared with conventional dosage. CONCLUSIONS: Individualized bowel preparation could achieve both satisfactory image quality and patients' acceptance thus might be an acceptable alternative in CTE.

4.
Nanomedicine (Lond) ; 19(1): 43-58, 2024 01.
Article En | MEDLINE | ID: mdl-38197371

Aim: To fabricate and characterize metformin-loaded PLGA nanoparticles and investigate their inhibitory effect on HepG2 cells. Materials & methods: The nanoparticles were prepared using a double emulsification method, then characterized and subjected to a series of in vitro assays on HepG2 cells. Results: The nanoparticles were ~277.9 nm in size, and the entrapment efficiency and drug loading of metformin were 31.3 and 14.4%, respectively. In vitro studies suggested that the nanoparticles showed a higher inhibitory effect on HepG2 cells compared with metformin alone, mainly attributed to its blockage of autophagy, and ultimately result in cell cycle inhibition. Conclusion: The metformin-loaded PLGA nanoparticles could inhibit mTOR activity, increase p53 levels and decrease HIF1A levels, which ultimately caused HepG2 cell cycle arrest.


Metformin, a well-known drug for the treatment of diabetes, has potential anticancer effects. Our experiment is fabricating metformin into nanoformulations (tiny particles) to enhance its anticancer effect. Cancer cells respond to nutrient-deficient environments by autophagy, this involves breaking down internal structures to scavenge for nutrients, which is one of the reasons why cancer cells are so resilient. If we can interfere with this autophagy of cancer cells, we can reduce the viability of cancer cells. Speaking of autophagy, we have to mention lysosomes, which are acidic organelles within the cell that are the end point of autophagy. Lysosomes need to maintain an acidic environment to ensure the activity of various enzymes within them. These enzymes break down a variety of biological components into 'building blocks' which can be used to make other structures. Our study found that the nanoformulation disrupts the lysosomal acidic environment and thus causes autophagy blockage. As a result, cancer cells are unable to cope with nutrient deficiencies through autophagy and suffer the negative effects of autophagy blockage, such as the inability to degrade damaged organelles and proteins within the cancer cell. This causes the growth and proliferation of cancer cells to slow down and results in the death of the cancer cells.


Metformin , Nanoparticles , Humans , Metformin/pharmacology , Hep G2 Cells , Cell Line, Tumor , Cell Cycle Checkpoints , Autophagy , Apoptosis
5.
Inflamm Bowel Dis ; 30(1): 114-124, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-37454276

BACKGROUND: Mucosal healing is one of the principal therapeutic targets for ulcerative colitis (UC). Mitochondria are dynamic organelles that undergo constant fusion and fission; however, the process that is most conducive to mucosal healing remains unclear. This study investigated the role of mitochondrial fission in mucosal healing in UC patients. METHODS: Quantitative polymerase chain reaction, Western blotting, and immunostaining were used to detect mitochondrial fission in UC patients and a dextran sulfate sodium-induced colitis model. Colonic organoids were used to investigate the role of mitochondrial fission in butyrate metabolism. Enzyme activity assays were performed to identify the key proteins involved in this mechanism. RESULTS: It was found that inhibition of mitochondrial fission promoted mucosal healing in mice and that there was an increase in mitochondrial fission in colonic epithelial cells of UC patients. Excessive fission inhibits stem cell proliferation by impairing butyrate metabolism in colonic organoids. The mitochondrial fission antagonist P110 failed to promote mucosal healing in antibiotic-treated mice, and the addition of exogenous butyrate reversed this effect. Increased butyrate exposure in the colonic stem cell niche has also been observed in UC patients. Mechanistically, enzyme activity assays on colonic organoids revealed that excessive fission inhibits mitochondrial acetoacetyl-CoA thiolase activity via reactive oxygen species. CONCLUSIONS: Collectively, these data indicate that excessive mitochondrial fission suppresses mucosal repair by inhibiting butyrate metabolism and provides a potential target for mucosal healing in patients with ulcerative colitis.


Colitis, Ulcerative , Humans , Animals , Mice , Colitis, Ulcerative/drug therapy , Mitochondrial Dynamics , Intestinal Mucosa/metabolism , Butyrates/pharmacology , Butyrates/metabolism
6.
Environ Monit Assess ; 195(10): 1193, 2023 Sep 12.
Article En | MEDLINE | ID: mdl-37698692

The present study investigated the bioaccumulation and translocation of mercury (Hg) and chromium (Cr) in Yunyan 87 flue-cured tobacco (Nicotiana tabacum) and assessed the influence of soil pH on the metal uptake by plant organs at the field scale. The study was conducted in 4 different regions selected from Sichuan Province, China: Guangyuan, Luzhou, Panzhihua, and Yibin. The results revealed that Hg highly contaminated Yibin soils at 0.29 mg kg-1 and by Cr at 147 mg kg-1, which is above the permissible limit. The levels of Hg in tobacco plant organs were predominantly in the order of leaves > root > stem. The overall trend for Cr contents in tobacco organs was in the order of root > leaves > stem. The results of an index of bioaccumulation (IBA) and translocation factor (TF) showed that the values observed in Panzhihua and Guangyuan tobacco leaves were generally higher, despite the low levels of soil contamination. The linear mixed model (LMM) demonstrated that the log of Hg IBA in tobacco organs was likely to decrease with soil pH increase, whereas the log of Cr IBA only decreased in the root but gradually increased in the aerial parts with soil pH increase. The total random variation in the log of metals' IBA due to regions indicated that for Hg, 33.42% of the variation was explained by regional differences, while for Cr, only 13% was accounted. The results suggested that Yibin and Luzhou need to correct the soil acidity if they are set to reduce Hg contamination in tobacco-growing soils. Guangyuan and Panzhihua need efforts to keep the soil pH on track to avoid high contamination levels, and effective measures of soil nutrients supply are required to produce high tobacco leaf quality free from heavy metal content. The findings of this study may be used to ascertain regional differences in heavy metals, particularly Hg and Cr uptake by tobacco plant organs, and to prevent the cultivation areas contamination through soil pH monitoring.


Chromium , Mercury , Nicotiana , Bioaccumulation , Environmental Monitoring , China , Soil , Hydrogen-Ion Concentration
7.
Bioorg Chem ; 138: 106654, 2023 09.
Article En | MEDLINE | ID: mdl-37300959

Parkinson's disease (PD) is a progressive neurodegenerative disorder with a complex etiology. Neuroinflammation and oxidative stress are important factors driving the progression of PD. It has been reported that 1,3,4-oxadiazole and flavone derivatives have numerous biological functions, especially in the aspect of anti-inflammatory and antioxidant. Based on the strategy of pharmacodynamic combination, we introduced 1,3,4-oxadiazole moiety into the flavonoid backbone, designed and synthesized a series of novel flavonoid 1,3,4-oxadiazole derivatives. Further, we evaluated their toxicity, anti-inflammatory and antioxidant activities using BV2 microglia. Following a comprehensive analysis, compound F12 showed the best pharmacological activity. In vivo, we induced the classical PD animal model by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into C57/BL6J mice. Our results showed that compound F12 ameliorated MPTP-induced dysfunction in mice. Further, compound F12 reduced oxidative stress by promoting the nucleation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inflammatory response by inhibiting the nuclear translocation of nuclear factor-κB (NF-κB) in vivo and in vitro. Meanwhile, compound F12 inhibited the mitochondrial apoptotic pathway to rescue microglia inflammation-mediated loss of dopaminergic neurons. In conclusion, compound F12 reduced oxidative stress and inflammation and could be as a potential agent for PD treatment.


Neuroprotective Agents , Parkinson Disease , Mice , Animals , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , NF-kappa B/metabolism , NF-E2-Related Factor 2/metabolism , Antioxidants/pharmacology , Flavonoids/pharmacology , Flavonoids/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Signal Transduction , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Disease Models, Animal , Mice, Inbred C57BL
8.
Leuk Lymphoma ; 64(8): 1400-1413, 2023.
Article En | MEDLINE | ID: mdl-37259867

Acute myeloid leukemia (AML) is a hematological malignancy with strong heterogeneity. Immune disorders are a feature of various malignancies, including AML. Interleukins (ILs) and other cytokines participate in a series of biological processes of immune disorders in the microenvironment, and serve as a bridge for communication between various cellular components in the immune system. The role of ILs in AML is complex and pleiotropic. It can not only play an anti-AML role by enhancing anti-leukemia immunity and directly inducing AML cell apoptosis, but also promote the growth, proliferation and drug resistance of AML. These properties of ILs can be used to explore their potential efficacy in disease monitoring, prognosis assessment, and development of new treatment strategies for AML. This review aims to clarify some of the complex roles of ILs in AML and their clinical applications.


Immune System Diseases , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Interleukins , Cytokines , Tumor Microenvironment
9.
Chemosphere ; 336: 139274, 2023 Sep.
Article En | MEDLINE | ID: mdl-37343637

Hexavalent chromium (Cr(VI)) is a toxic heavy metal and its mobility and bioaccessibility in soils are influenced by soil properties. In this study, the soil pH and organic carbon contents of Ultisol, Alfisol, and Inceptisol were adjusted before they were polluted with 230 mg kg-1 Cr(VI). Alkaline digestion, sequential extraction, and an in vitro experiment were conducted to study the valence state, species, and bioaccessibility of Cr in the soils. The results showed that a high soil pH was not favorable for reduction of Cr(VI); therefore the Cr(VI) and exchangeable Cr contents were positively related to soil pH. Soil organic carbon promoted the reduction of Cr(VI). Almost all Cr(VI) was reduced to Cr(III) when the soil organic carbon content reached 10 g kg-1. Chromium bioaccessibility in simulated gastric and intestinal phase solutions was influenced by Cr(VI) and Cr(III) adsorption/desorption, dissolution/precipitation, and redox reactions. Chromium bioaccessibility differences between the gastric and intestinal phases were associated with the Cr(VI)/Cr(III) ratio. Acidic conditions and a high organic carbon content promoted the conversion of Cr(VI) to Cr(III). When soil pH was increased from 4.01 to 5.85, Cr(VI) in Alfisol without the addition of humic acid increased from 96.38 to 174.78 mg kg-1, the exchangeable Cr proportion increased from 9.7% to 22.6%, and Cr bioaccessibility increased from 41.29% to 49.14% in the gastric phase and from 41.32% to 48.24% in the intestinal phase. When the organic carbon content increased from 3.95 to 9.28 g kg-1 in Alfisol, Cr(VI) content decreased from 167.66 to 20.52 mg kg-1, which led to a decrease in Cr bioaccessibility from 49.15% to 13.8% in the gastric phase and from 45.85% to 7.67% in the intestinal phase. Therefore, acidic conditions and increasing soil organic carbon levels can reduce the health risk posed by Cr in soils.


Soil Pollutants , Soil , Soil/chemistry , Carbon/chemistry , Soil Pollutants/analysis , Chromium/chemistry
10.
Acta Pharmacol Sin ; 44(10): 2065-2074, 2023 Oct.
Article En | MEDLINE | ID: mdl-37225845

Diabetes-related vascular complications include diabetic cardiovascular diseases (CVD), diabetic nephropathy (DN) and diabetic retinopathy, etc. DN can promote the process of end-stage renal disease. On the other hand, atherosclerosis accelerates kidney damage. It is really an urge to explore the mechanisms of diabetes-exacerbated atherosclerosis as well as new agents for treatment of diabetes-exacerbated atherosclerosis and the complications. In this study we investigated the therapeutic effects of fisetin, a natural flavonoid from fruits and vegetables, on kidney injury caused by streptozotocin (STZ)-induced diabetic atherosclerosis in low density lipoprotein receptor deficient (LDLR-/-) mice. Diabetes was induced in LDLR-/- mice by injecting STZ, and the mice were fed high-fat diet (HFD) containing fisetin for 12 weeks. We found that fisetin treatment effectively attenuated diabetes-exacerbated atherosclerosis. Furthermore, we showed that fisetin treatment significantly ameliorated atherosclerosis-enhanced diabetic kidney injury, evidenced by regulating uric acid, urea and creatinine levels in urine and serum, and ameliorating morphological damages and fibrosis in the kidney. In addition, we found that the improvement of glomerular function by fisetin was mediated by reducing the production of reactive oxygen species (ROS), advanced glycosylation end products (AGEs) and inflammatory cytokines. Furthermore, fisetin treatment reduced accumulation of extracellular matrix (ECM) in the kidney by inhibiting the expression of vascular endothelial growth factor A (VEGFA), fibronectin and collagens, while enhancing matrix metalloproteinases 2 (MMP2) and MMP9, which was mainly mediated by inactivating transforming growth factor ß (TGFß)/SMAD family member 2/3 (Smad2/3) pathways. In both in vivo and in vitro experiments, we demonstrated that the therapeutic effects of fisetin on kidney fibrosis resulted from inhibiting CD36 expression. In conclusion, our results suggest that fisetin is a promising natural agent for the treatment of renal injury caused by diabetes and atherosclerosis. We reveal that fisetin is an inhibitor of CD36 for reducing the progression of kidney fibrosis, and fisetin-regulated CD36 may be a therapeutic target for the treatment of renal fibrosis.


Diabetes Mellitus, Experimental , Diabetic Nephropathies , Animals , Mice , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Fibrosis/drug therapy , Kidney/pathology , Signal Transduction , Vascular Endothelial Growth Factor A/metabolism , CD36 Antigens/drug effects
11.
Acta Pharmacol Sin ; 44(8): 1625-1636, 2023 Aug.
Article En | MEDLINE | ID: mdl-36997664

Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1ß and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21ECKO) mice, VD3 and nicotine-induced vascular calcification was significantly reduced. Our results suggest that TCF21 aggravates vascular calcification by activating IL-6/STAT3 signaling and interplay between VSMC and EC, which provides new insights into the pathogenesis of vascular calcification. TCF21 enhances vascular calcification by activating the IL-6-STAT3 signaling pathway. TCF21 inhibition may be a new potential therapeutic strategy for the prevention and treatment of vascular calcification.


Plaque, Atherosclerotic , Vascular Calcification , Animals , Humans , Mice , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cells, Cultured , Endothelial Cells/metabolism , Interleukin-6/metabolism , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Osteogenesis , Plaque, Atherosclerotic/metabolism , Signal Transduction , STAT3 Transcription Factor/metabolism , Vascular Calcification/genetics , Vascular Calcification/pathology
12.
Acta Pharmacol Sin ; 44(2): 308-320, 2023 Feb.
Article En | MEDLINE | ID: mdl-35948752

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.


Migraine Disorders , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Nitroglycerin/adverse effects , Hypoxia-Inducible Factor 1, alpha Subunit , Pain Threshold , Migraine Disorders/chemically induced , Migraine Disorders/drug therapy , Migraine Disorders/metabolism , Inflammation/chemically induced , Inflammation/drug therapy
13.
Acta Pharmacol Sin ; 44(3): 635-646, 2023 Mar.
Article En | MEDLINE | ID: mdl-35995867

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 µM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.


Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver X Receptors/metabolism , Liver Neoplasms/pathology , ErbB Receptors/metabolism , NF-kappa B/metabolism , Cell Line, Tumor , Calcium-Binding Proteins
14.
Chemosphere ; 309(Pt 1): 136749, 2022 Dec.
Article En | MEDLINE | ID: mdl-36209864

Phosphorus (P) availability in highly weathered soils is significantly influenced by the contents of iron (Fe)/aluminum (Al) oxides, clay minerals, and organic matter. With the increasing interest in biofertilizers (e.g. chitosan), it is important to understand how they affect P adsorption profiles on colloids of weathered soils rich in Fe/Al oxides. Thus, the effect of chitosan on the adsorption of P to colloids of hematite, gibbsite, Oxisol, and Ultisol was studied through electrokinetic measurements, spectroscopic analysis, and adsorption edge/isotherm profiles. The presence of chitosan significantly improved the surface positive charge and the decreasing trend of surface positive charge was slower for chitosan-treated colloids compared to the control with increasing pH. At pH 5.0, all the colloids were positively charged, with the oxides containing more positve charges than the soil colloids. At this pH value, the surface coverage capacity of P was 99.1, 61.6, 50.5, and 37.5 mmol kg⁻1 for Oxisol, Ultisol, hematite, and gibbsite, respectively. This suggests that clay minerals in soil colloids were vital in enhancing P adsorption. In the presence of chitosan, the surface coverage capacity of P was increased by 111%, 173%, 647%, and 488% for Oxisol, Ultisol, gibbsite, and hematite, respectively. Drawing inferences from spectroscopic analysis, citric acid desorption profile, and zeta potential analysis, we suggest that chitosan (CH) enhanced P adsorption by promoting the formation of (i) citric acid "undisplaceable" inner-sphere P complexes such as [Colloid-OP-O-CH] and [Colloid-OP-N-CH], (ii) citric acid "displaceable" outer-sphere P complexes such as {[Colloid-O-CH]-OP} and {[Colloid-N-CH]-OP}, and (iii) water "leachable or soluble" P complexes such as {[Colloid-CH]+PO4³â»} and {[Colloid-OP]⁻CH+}. Thus, applying chitosan as a biofertilizer (source of N) along with P in highly weathered soils could improve P availability while reducing P leaching.


Chitosan , Soil Pollutants , Phosphates/chemistry , Soil Pollutants/analysis , Clay , Aluminum , Soil/chemistry , Colloids/chemistry , Phosphorus , Minerals , Iron , Oxides , Citric Acid , Water
15.
Sci Rep ; 12(1): 18110, 2022 10 27.
Article En | MEDLINE | ID: mdl-36302888

Geographical, environmental and pollution conditions affect facial skin health, but their effects on skin appearance have not been elucidated. This study aimed to describe the skin barrier and skin tone characteristics of Chinese subjects according to lifestyle and environmental conditions using in vitro measurements. In total, 1092 women aged 22-42 years were recruited from 7 representative Chinese cities. Eight skin parameters (hydration, sebum, pH, transdermal water loss, individual type angle, melanin index, erythema index, yellowness) were measured using noninvasive instruments; individual lifestyle data were also collected. Data on four meteorological factors (air temperature, relative humidity, sunshine duration, wind speed) and seven air pollution indicators (air quality index, fine particulate matter, breathable particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone) were collected in each city from the China Meteorological Administration. Facial skin characteristics differed significantly between cities. Facial skin barrier characteristics and skin tones showed regional differences, with a better skin barrier associated with the western region, as indicated by high skin hydration and sebum secretion and a low pH value. According to the value of transdermal water loss, lighter and darker skin tones were found in the western and southern regions, respectively. Environmental conditions affected facial skin status. Air pollution induced facial skin issues, with fine particulate matter and nitrogen dioxide contributing the most. Individual lifestyles affected the facial skin barrier and skin tone.


Air Pollutants , Air Pollution , Female , Humans , Air Pollutants/adverse effects , Air Pollutants/analysis , Cross-Sectional Studies , Particulate Matter/adverse effects , Particulate Matter/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Nitrogen Dioxide/analysis , Sulfur Dioxide/analysis , Cities , China/epidemiology , Water , Life Style , Environmental Monitoring
16.
Front Med (Lausanne) ; 9: 870926, 2022.
Article En | MEDLINE | ID: mdl-35572984

Background: Facial skin is exposed to the environment, which marks it with obvious signs of aging. Based on multi-dimensional non-invasive evaluation data, female facial skin can be characterized in detail. However, there are few studies on the general aging rules of facial skin. Most skin aging studies divide the ages into 5-10-year intervals, so they have lacked dynamic matching with facial skin aging. Aim: To explore facial skin aging rules, discuss the main parameters of facial skin aging, propose an unequal-distance aging division method based on the main skin parameters, and study the skin characteristics of Chinese women of different aging stages. Methods: We comprehensively described the skin status as 24 non-invasive skin parameters belonging to five dimensions: skin wrinkles, texture, stain, color and barrier function. We performed polynomial fitting on the 21 skin parameters that were significantly correlated with age and derived the rules of aging in the different dimensions. Based on the wrinkle dimension, the facial skin aging process was divided into four stages, and the skin characteristics of the different stages were compared. Results: Skin wrinkles increased, texture deteriorated, acne decreased, pigment spots increased, skin tone darkened, and sebum secretion decreased with age, according to the polynomial fitting. The aging stage was divided into an incubation period (18-30 years old), an aging occurrence period (31-42 years old), a rapid aging period (43-47 years old), and a stable aging period (48-60 years old), according to the wrinkles. Different aging stages had different skin characteristics. Conclusion: The incubation period is the critical period for the appearance of skin stains; the skin texture gradually deteriorates during the aging occurrence period; the rapid aging period is a critical period for the aging of skin parameters; skin status during the stable aging period is the worst.

17.
Chemosphere ; 301: 134674, 2022 Aug.
Article En | MEDLINE | ID: mdl-35461893

To explore the effects of the increases in pH and pH buffering capacity (pHBC) induced by crop residue biochars on the changes in soil available Cd content, six acidic paddy soils developed from different parents were amended with seeded sunflower plate biochar (SSPBC), peanut straw biochar (PSBC) and corn straw biochar (CSBC). The pH, pHBC, and available Cd of the soils were measured after laboratory incubation. The results showed that the incorporation of crop residue biochars led to the increases in soil pH and pHBC, but a decrease in soil available Cd content. The decreasing order of available Cd content was SSPBC > PSBC > CSBC and was consistent with the changes in soil pH induced by the biochars. During submerging and draining, soil pH increased first and then declined, however the content of available Cd decreased first and then increased significantly. Soil pH in the treatments with biochars showed little change during draining, which was different from the control without the biochars added. This was attributed to the enhancing effect of the biochars on soil pHBC. Also, there was a significant negative correlation between the change in available Cd content and soil pHBC during submerging/draining alternation and suggested that higher pHBC corresponded to smaller soil available Cd content. Consequently, the amount of Cd absorbed by rice was reduced, thereby reducing the potential risk of soil Cd to humans. These results can provide useful references for the remediation of Cd-contaminated paddy soils.


Oryza , Soil Pollutants , Acids/chemistry , Arachis , Cadmium/analysis , Charcoal/chemistry , Humans , Hydrogen-Ion Concentration , Oryza/chemistry , Soil/chemistry , Soil Pollutants/analysis , Zea mays
18.
Surg Endosc ; 36(7): 5510-5517, 2022 07.
Article En | MEDLINE | ID: mdl-35325289

BACKGROUND: Using conventional endoscope to perform endoscopic submucosal dissection (ESD) is difficult because of the one-handed operation and blind dissection caused by gravity. Poor visualization of the submucosal plane causes ESD to be associated with a high risk of bleeding and perforation. This study aimed to develop a novel ESD-assistive robot system and to evaluate its efficacy. METHODS: A novel flexible auxiliary single-arm transluminal endoscopic robot (FASTER) was developed. A total of 36 artificial lesions in ex vivo porcine stomachs were removed using the FASTER-assisted ESD method (n = 18) and the conventional ESD method (n = 18). Lesions were 2 cm or 4 cm in diameter, located on the anterior and posterior walls of the antrum. Primary outcome measurements were dissection time and dissection speed. RESULTS: The dissection time in FASTER-assisted ESD was significantly shorter than that in conventional ESD (7 min vs 13 min, p = 0.012), mainly because of the faster dissection speed (148.6 vs 97.0 mm2/min, p = 0.002). The total procedure time in FASTER-assisted ESD was shorter than that in conventional ESD, but the difference was not significant (16 min vs 24 min, p = 0.252). Complete en bloc resection was achieved in all lesions. No perforations were detected. The FASTER exhibited the ability of regrasp, multidirectional traction, and proper tension control during ESD. CONCLUSION: FASTER significantly increased the dissection speed by providing proper traction and achieving good submucosal vision. This new device is expected to facilitate ESD in clinical practice.


Endoscopic Mucosal Resection , Robotics , Stomach Neoplasms , Animals , Dissection/methods , Endoscopic Mucosal Resection/methods , Humans , Stomach Neoplasms/surgery , Swine , Traction , Treatment Outcome
19.
Helicobacter ; 27(2): e12880, 2022 Apr.
Article En | MEDLINE | ID: mdl-35150600

BACKGROUND: Helicobacter pylori (H. pylori) infections are of serious concern due to the associated risk of gastric cancer. However, many patients have poor medication and therapy compliance, which makes it difficult to eradicate their infections. This points to the need for stronger educational interventions aimed at enhancing compliance, thus increasing the potential for treatment success. As such, this study conducted a meta-analysis to clarify the effects of enhanced patient education (EPE) programs for H. pylori. MATERIALS AND METHODS: We searched electronic databases (PubMed, EMBASE, Web of Science, and Cochrane Library) for randomized controlled trials (RCTs) on health education for patients infected with H. pylori from inception to June 2021. The primary outcome was the eradication rate of H. pylori, while the secondary outcomes included the incidence of individual adverse symptoms, treatment compliance, clinical symptom remission after treatment, and patient satisfaction. We used the fixed or random-effects model to pool the risk ratio (RR), with 95% confidence interval. We also conducted sensitivity and subgroup analyses. RESULTS: Our search returned seven relevant studies across a total of 1,433 patients. Compared with controls, EPE was significantly associated with improved H. pylori eradication rates (RR = 1.16, 95%CI: 1.04-1.29, p = 0.006) and patient compliance (RR = 1.48, 95%CI: 1.14-1.93, p = 0.003). A subgroup analysis also showed that EPE benefits were consistent across patients with different eradication programs, WeChat intervention plans, and intervention frequencies (p < 0.05). However, there were no significant differences in the total adverse effects, common side effects (diarrhea, nausea, abdominal pain, taste disorder, and skin rash), or discontinuation rate (p > 0.05). CONCLUSIONS: Patient education is inexpensive, safe, and convenient. In this context, our findings suggest that enhanced educational interventions have positive effects on both the H. pylori eradication rate and adherence among infected patients, and thus constitute promising complements to clinical treatment regimens.


Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Anti-Bacterial Agents/pharmacology , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Humans , Stomach Neoplasms/drug therapy
20.
Gastrointest Endosc ; 96(1): 140-147, 2022 07.
Article En | MEDLINE | ID: mdl-35065045

BACKGROUND AND AIMS: Effective countertraction is a main challenging issue in endoscopic submucosal dissection (ESD). Several countertraction methods have been developed to address this issue. The aim of this study was to compare the efficacy of ESD using a novel simplified robot, the flexible auxiliary single-arm transluminal endoscopic robot (FASTER), with a traditional technique. METHODS: This was a prospective, randomized animal study. Forty-eight ESDs in 6 pigs were carried out at 8 different locations (gastric antrum, gastric body, lower esophagus, and middle esophagus) by the conventional method (n = 24) and by the FASTER-assisted method (n = 24). The primary outcomes were total procedure time, dissection time, and rate of direct-vision dissection. Secondary endpoints were completeness of en-bloc resection and adverse event rate. RESULTS: The total procedure time was significantly shorter in FASTER-assisted ESD than in conventional ESD (18.8 vs 32.8 minutes; P < .001). In contrast to the median direct-vision dissection rate of 73% with conventional ESD, the FASTER-assisted group had a significantly higher rate of 96% (P < .001). The number of sites of muscular damage was significantly lower using the FASTER-assisted method than the conventional method (6 vs 21, respectively; P = .018). This improvement was more apparent in esophageal lesions compared with gastric lesions. CONCLUSIONS: This study demonstrated that using a simplified robot during ESD is technically feasible and enables the endoscopist to dynamically use countertraction. This device could significantly reduce procedure time compared with conventional ESD techniques.


Endoscopic Mucosal Resection , Robotics , Stomach Diseases , Animals , Dissection/methods , Endoscopic Mucosal Resection/methods , Esophagus/surgery , Humans , Prospective Studies , Swine , Treatment Outcome
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