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1.
iScience ; 27(5): 109778, 2024 May 17.
Article En | MEDLINE | ID: mdl-38746665

Depressive symptoms usually precede the cognitive decline in Alzheimer disease (AD) and worsen the clinical outcome. However, the neural circuitry mediating early emotional dysfunction, especially depressive symptoms in AD, remains elusive. Anterior cingulate cortex (ACC) is closely related to depression and vulnerable in AD. By quantitative whole-brain mapping and electrophysiological recording, we found that the decreased axonal calcium activity in neurons of ACC and the glutamatergic projection from ACC to the ventral hippocampal CA1 (vCA1) is significantly impaired in 3-month-old 5×FAD mice, which exhibit depressive-like phenotype before cognition defects in early stage. The activation of ACC-vCA1 circuit by chemogenetic manipulation efficiently ameliorated the early depressive-like behaviors in 5×FAD mice. We further identified the upregulated neuregulin-1 (Nrg1) in ACC impaired the excitatory synaptic transmission from the ACC to vCA1 in AD. Our work reveals the role of ACC-vCA1 circuit in regulating AD associated depression symptom in a mouse model of AD.

2.
J Endocrinol ; 260(2)2024 02 01.
Article En | MEDLINE | ID: mdl-37991884

Aging-related reduction in androgen levels may be a possible risk factor for neurodegenerative diseases and contribute to cognitive impairment. Androgens may affect synaptic function and cognition in an androgen receptor (AR)-independent manner; however, the mechanisms connecting theses effects are unknown. Therefore, we used testicular feminization mutation (Tfm) male mice, a model with AR mutation, to test the effects of testosterone on synaptic function and cognition. Our results showed that testosterone ameliorated spatial memory deficit and neuronal damage, and increased dendritic spines density and postsynaptic density protein 95 (PSD95) and glutamate receptor 1 (GluA1) expression in the hippocampus of Tfm male mice. And these effects of testosterone were not inhibited by anastrozole, which suppressed conversion of testosterone to estradiol. Mechanistically, testosterone activated the extracellular signal-related kinase 1/2 (Erk1/2) and cyclic adenosine monophosphate response element-binding protein (CREB) in the hippocampus of Tfm male mice. Meanwhile, Erk1/2 inhibitor SCH772984 blocked the upregulation of phospho-CREB, PSD95, and GluA1 induced by testosterone in HT22 cells pretreated with flutamide, an androgen antagonist. Collectively, our data indicate that testosterone may ameliorate hippocampal synaptic damage and spatial memory deficit by activating the Erk1/2-CREB signaling pathway in an AR-independent manner.


Receptors, Androgen , Testosterone , Animals , Male , Mice , Androgens/pharmacology , Androgens/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Hippocampus/metabolism , Memory Disorders/drug therapy , Memory Disorders/genetics , Memory Disorders/metabolism , Receptors, Androgen/metabolism , Testosterone/metabolism
3.
Front Immunol ; 14: 1282734, 2023.
Article En | MEDLINE | ID: mdl-37928523

Introduction: Copper metabolism encompasses all cellular metabolic processes involving copper ions and plays a significant role in the pathogenesis of diseases, including cancer. Furthermore, copper is intricately involved in various processes related to nucleotide metabolism. However, a comprehensive analysis of copper metabolism in gliomas remains lacking despite its importance. Methods: To address this gap, glioma patients were stratified based on the expression levels of copper metabolism-related genes. By utilizing machine learning techniques, a novel copper metabolism-associated biomarker was developed. The potential of this biomarker in prognosis, mutation analysis, and predicting immunotherapy response efficiency in gliomas was systematically investigated. Results: Notably, IGFBP2, identified as a glioma tumor promoter, was found to promote disease progression and influence immunotherapy response. Additionally, glioma-derived IGFBP2 was observed to enhance microglial migration. High IGFBP2 expression in GBM cells facilitated macrophage interactions through the EGFR, CD63, ITGB1, and CD44 signaling pathways. Discussion: Overall, the copper metabolism-associated biomarker shows promising potential to enhance the clinical management of gliomas, offering valuable insights into disease prognosis and treatment strategies.


Brain Neoplasms , Glioma , Humans , Brain Neoplasms/genetics , Copper , Glioma/genetics , Biomarkers , Immunotherapy
4.
Cancer Cell Int ; 23(1): 246, 2023 Oct 19.
Article En | MEDLINE | ID: mdl-37858068

BACKGROUND: RAD51B plays a significant role in homologous recombination-mediated repair of DNA double-strand breaks. Many enhancer variants are involved in cancer development and progression. However, the significance of enhancer variants of RAD51B in glioma susceptibility and progression remains unclear. METHODS: A case-control study consisting of 1056 individuals was conducted to evaluate the associations of enhancer variants of RAD51B with glioma susceptibility and progression. Sequenom MassARRAY technology was used for genotyping. The function of enhancer variants was explored by biochemical assays. RESULTS: A significantly decreased risk of glioma was associated with rs6573816 GC genotype compared with rs6573816 GG genotype (OR = 0.66, 95% CI 0.45-0.97; P = 0.034). Multivariable Cox regression revealed that rs6573816 was significantly associated with glioma progression in a sex-dependent manner. Worse PFS was found in the male patients with high grade glioma carrying rs6573816 GC or CC genotype (HR = 2.28, 95% CI 1.14-4.57; P = 0.020). The rs6573816 C allele repressed enhancer activity by affecting transcription factor POU2F1 binding, which resulted in lower expression of RAD51B. Remarkably attenuated expression of RAD51B was observed following POU2F1 knockdown. Consistently, positive correlation between the expression of POU2F1 and RAD51B was found in lymphoblastic cells and glioma tissues. CONCLUSIONS: These results indicate that an enhancer variant of RAD51B rs6573816 influences enhancer activity by changing a POU2F1 binding site and confers susceptibility and progression to glioma.

5.
PLoS Biol ; 21(3): e3002033, 2023 03.
Article En | MEDLINE | ID: mdl-36928253

Aging is a systemic process, which is a risk factor for impaired physiological functions, and finally death. The molecular mechanisms driving aging process and the associated cognitive decline are not fully understood. The hypothalamus acts as the arbiter that orchestrates systemic aging through neuroinflammatory signaling. Our recent findings revealed that Menin plays important roles in neuroinflammation and brain development. Here, we found that the hypothalamic Menin signaling diminished in aged mice, which correlates with systemic aging and cognitive deficits. Restoring Menin expression in ventromedial nucleus of hypothalamus (VMH) of aged mice extended lifespan, improved learning and memory, and ameliorated aging biomarkers, while inhibiting Menin in VMH of middle-aged mice induced premature aging and accelerated cognitive decline. We further found that Menin epigenetically regulates neuroinflammatory and metabolic pathways, including D-serine metabolism. Aging-associated Menin reduction led to impaired D-serine release by VMH-hippocampus neural circuit, while D-serine supplement rescued cognitive decline in aged mice. Collectively, VMH Menin serves as a key regulator of systemic aging and aging-related cognitive decline.


Aging , Cognitive Dysfunction , Hypothalamus , Animals , Mice , Aging/genetics , Aging/metabolism , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Hypothalamus/metabolism , Serine/metabolism , Transcription Factors/metabolism
6.
Chemosphere ; 318: 137970, 2023 Mar.
Article En | MEDLINE | ID: mdl-36708784

In this work, a heterogeneous catalyst of CuxO was rationally designed by using Cu-based metal organic frameworks (marked Cu-BDC) as the template, and was used to degrade tetracycline (TC) via activation of peroxymonosulfate (PMS). The optimal CuxO-350 showed excellent catalytic efficiency for TC degradation, and the reaction rate constant (0.104 min-1) was 8 times higher than that (0.013 min-1) of raw Cu-BDC. The characterization observations confirmed that CuxO-350 possessed multiple valence states (CuO and Cu2O) and oxygen vacancies (Ov), both of which were favorable for the activation of PMS, resulting in promoting the generation of active species in the CuxO-350 + PMS system. Different from the free radical pathway in Cu-BDC + PMS system, a radical-nonradical coupling process was detected in the CuxO-350 + PMS system, which was confirmed by quenching experiments and EPR measurements. Moreover, the toxicity prediction showed that the toxicity of degradation intermediates declined compared with TC. This work not only opened up a new strategy for the rational design and preparation of high-efficient catalysts by employing metal organic frameworks precursors, but also offered an insight into the reaction mechanism of PMS activation through a radical-nonradical coupling process catalyzed by CuxO-350 derived from Cu-BDC.


Metal-Organic Frameworks , Peroxides , Oxygen , Anti-Bacterial Agents/pharmacology , Tetracycline
7.
Ear Nose Throat J ; 102(2): NP76-NP81, 2023 Feb.
Article En | MEDLINE | ID: mdl-33530739

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) is extremely rare, and most of them are immediately treated for radical resection. However, the information concerning its natural history remains unclear. In this report, we presented a patient with parapharyngeal SFT/HPC, who was not immediately treated with surgical resection at first diagnosis. After approximately 3 years, the tumor volume doubling time (TVDT) and specific growth rate (SGR) could be measured through 3 serial magnetic resonance imagings. The TVDTs in the early and late pretreatment stages were 350 and 180 days, respectively, while the SGRs were 0.002 and 0.003, respectively. The growth rate of this disease entity is generally slow and may accelerate in the disease process.


Hemangiopericytoma , Solitary Fibrous Tumors , Humans , Prognosis , Hemangiopericytoma/diagnostic imaging , Hemangiopericytoma/surgery , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/surgery , Magnetic Resonance Imaging , Diagnosis, Differential
8.
Quant Imaging Med Surg ; 12(5): 2841-2854, 2022 May.
Article En | MEDLINE | ID: mdl-35502385

Background: Salivary gland cancer (SGC) is relatively rare and constitutes a variety of histological subtypes. Previously published studies of SGC patients suggest that postoperative radiation using conventional radiotherapy (RT) or 3-dimensional (3D) conformal radiotherapy may have led to suboptimal oncological outcomes. Methods: We identified 60 patients with major SGC treated with surgery followed by postoperative intensity-modulated radiotherapy (IMRT). Data for overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), prognostic factors, and treatment-related toxicities were analyzed. Survival was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results: With a median follow-up of 55.5 months, based on Kaplan-Meier analyses, the OS and PFS rates for SGC patients at 3, 5, and 10 years were 90.7%, 85.1%, and 85.1% and 80.1%, 72.7%, and 63.1%, respectively. The LRRFS and DMFS rates at 3, 5, and 10 years were 87.4%, 82.1%, and 82.1% and 85.3%, 78.4%, and 66.1%, respectively. In multivariable analysis (MVA), the node stage (N stage) was an independent predictor of PFS [P=0.047; hazard ratio (HR) =0.089]. A positive margin was a significant prognostic factor for PFS (P=0.036; HR =4.086), LRRFS (P=0.026; HR =5.064), and DMFS (P=0.011; HR =6.367). Major nerve involvement was significantly correlated with PFS (P=0.034; HR =2.394) and DMFS (P=0.008; HR =2.115). The interval from surgery to radiotherapy predicted PFS (P=0.036; HR =3.934) and DMFS (P=0.012; HR =6.231). Adenoid cystic carcinoma (ACC) was the most common histology (n=21; 35%). For ACC, the 5-year OS, PFS, LRRFS, and DMFS were 100%, 67.7%, 76.2%, and 90.2%, respectively. The most common acute toxicities were mucositis and dermatitis, and xerostomia was the most common late adverse event. Lung metastasis was the most common pattern of distant failure. Conclusions: N stage, positive margin, major nerve involvement, and interval from surgery to radiotherapy were important factors associated with PFS, LRRFS, and DMFS. Postoperative IMRT leads to improved survival for SGC patients, with acceptable toxicities.

9.
J Hazard Mater ; 428: 128244, 2022 04 15.
Article En | MEDLINE | ID: mdl-35032952

The threat caused by the misuse of antibiotics to ecology and human health has been aroused an extensive attention. Developing cost-effective techniques for removing antibiotics needs to put on the agenda. In current research, the degradation mechanism of sulfamethoxazole (SMX) by sulfidated nanoscale zerovalent iron (S-nZVI) driven persulfate, together with the potential risk of intermediates were studied. The degradation of SMX followed a pseudo-first order kinetics reaction with kobs at 0.1176 min-1. Both SO4•- and •OH were responsible for the degradation of SMX, and SO4•- was the predominant free radical. XPS analysis demonstrated that reduced sulfide species promoted the conversion of Fe (III) to Fe (II), resulting in the higher transformation rate of SMX. Six intermediates products were generated through hydroxylation, dehydration condensation, nucleophilic reaction, and hydrolysis. The risk of intermediates products is subsequently assessed using E. coli as a model microorganism. After E.coli exposure to intermediates for 24 h, the upmetabolism of carbohydrate, nucleotide, citrate acid cycle and downmetabolism of glutathione, sphingolipid, galactose by metabolomics analysis identified that SMX was effectively detoxified by oxidation treatment. These findings not only clarified the superiority of S-nZVI/persulfate, but also generated a novel insight into the security of advanced oxidation processes.


Sulfamethoxazole , Water Pollutants, Chemical , Escherichia coli , Humans , Iron , Metabolomics , Oxidation-Reduction , Risk Assessment , Sulfamethoxazole/toxicity , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity
10.
Eur Arch Otorhinolaryngol ; 279(3): 1519-1533, 2022 Mar.
Article En | MEDLINE | ID: mdl-34146150

PURPOSE: The incidence and mortality rate of nasopharyngeal carcinoma (NPC) has changed in recent years. Our goal is to determine the epidemiological pattern of NPC to help policymakers allocate limited medical resources. METHODS: Detailed information about NPC from 2009 to 2019 was collected from the Global Burden of Disease 2019 database. Age-standardized rates (ASRs) and corresponding estimated annual percentage changes (EAPCs) were calculated to assess NPC's incidence and mortality trends. RESULTS: Globally, there was a consistent increase in the NPC incidence cases from 2009 to 2019 (from 121.65 × 103 cases in 2009 to 176.50 × 103 cases in 2019, increasing by 45.09%). The age-standardized incidence rate (ASIR) of NPC increased from 1.81 in 2009 to 2.12 in 2019 (EAPC = 1.59, 95% CI 1.36-1.81). On the contrary, the mortality of NPC showed a downward trend (ASDR: 0.93 in 2009 and 0.86 in 2019; EAPC = - 0.63, 95% CI - 0.78 to - 0.48), and it was negatively correlated with the social demographic index (SDI) in most regions. Both incidence and mortality rates of high-incidence territories tended to be stable or decline. Males had significantly higher incidence and mortality of NPC than females. The number of patients with onset age greater than 50 years old accounted for the highest proportion. We found that smoking, occupational exposure to formaldehyde, and alcohol use were the main risk factors for NPC-related mortality. CONCLUSION: Globally, the incidence rate of NPC has been slightly increasing, while the mortality and disability-adjusted life years (DALYs) have been decreasing. NPC burden in high-middle and middle SDI areas was the heaviest. The current prevention strategy should be repositioned, and some countries should formulate more targeted approaches to reduce the current burden of NPC.


Global Burden of Disease , Nasopharyngeal Neoplasms , Female , Global Health , Humans , Incidence , Male , Middle Aged , Nasopharyngeal Carcinoma/epidemiology , Nasopharyngeal Neoplasms/epidemiology , Quality-Adjusted Life Years
11.
BMC Infect Dis ; 21(1): 1230, 2021 Dec 07.
Article En | MEDLINE | ID: mdl-34876042

BACKGROUND: Leptospirosis is a common infectious disease in tropical and semitropical regions, and it is typically neglected. Leptospirosis-associated acute diffuse alveolar hemorrhage is one of its fatal complications. The use of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing in the diagnosis of Leptospira interrogans infection has rarely been reported. CASE PRESENTATION: We present the case of a 62-year-old female who was transferred to our hospital with dyspnea, and severe hemoptysis and was supported by a tracheal intubation ventilator. Bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) reported Leptospira interrogans. A diagnosis of diffuse alveolar hemorrhage caused by leptospirosis was made. After immediately receiving antibiotics and hormone therapy, the patient achieved a complete recovery upon discharge. CONCLUSION: Leptospirosis presenting as severe diffuse alveolar hemorrhage is rare but should be considered in the differential diagnosis. mNGS can help identify pathogens and treat them early, which can improve prognosis.


Leptospirosis , Metagenomics , Female , Hemorrhage/diagnosis , High-Throughput Nucleotide Sequencing , Humans , Leptospirosis/diagnosis , Metagenome , Middle Aged
12.
Quant Imaging Med Surg ; 11(7): 3314-3326, 2021 Jul.
Article En | MEDLINE | ID: mdl-34249656

BACKGROUND: Whether to prophylactically irradiate the ipsilateral internal mammary chain (IMC) in post-mastectomy radiotherapy (PMRT) remains controversial because of equivocal clinical benefits against the added toxicities. Our previous study revealed that the cardiac dose was decreased during left-sided breast radiotherapy with abdominal deep inspiration breath-hold (aDIBH) as compared with free-breathing (FB) and thoracic deep inspiration breath-hold (tDIBH). Here we present the dosimetric advantage of aDIBH for patients undergoing PMRT with IMC coverage. METHODS: We prospectively analyzed 19 patients with left-sided breast cancer who underwent PMRT. Patients underwent computed tomography (CT) simulation under both free-breathing (FB) and aDIBH. The heart, left anterior descending coronary artery (LAD), lungs, and the contralateral breast was defined as organs at risk (OARs). Three-dimensional conformal radiation therapy (3D-CRT), inverse planning intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT) were used to calculate the doses received by both the planning target volume (PTV) and OARs, which were compared using the Wilcoxon signed-rank test. RESULTS: Compared with FB, the Dmean of the heart and LAD were respectively reduced by 3.5 Gy (P<0.003) and 8.9 Gy (P<0.001) in 3D-CRT, 2.6 Gy (P<0.001), and 7.8 Gy (P=0.001) in IMRT, 1.5 Gy (P<0.001) and 4.5 Gy (P=0.001) in VMAT plans under aDIBH. Among all these plans, the Dmean of the heart was lowest in aDIBH IMRT and 1.3 Gy lower than in aDIBH VMAT (P=0.002). aDIBH IMRT also resulted in a significantly reduced dose to the ipsilateral lung than plans under FB (P<0.05). Dmean and V5 to the contralateral lung and breast were higher in VMAT plans (P<0.05). CONCLUSIONS: Using an immobilization-assisted aDIBH technique, radiation doses to the heart can be kept at reasonably low levels even if IMC is included in the clinical target volume (CTV). Among 3D-CRT, IMRT, and VMAT plans, IMRT plus aDIBH results in the best heart-sparing effect. We recommend that the aDIBH technique be routinely applied in suitable patients if the IMC is irradiated.

13.
Front Pediatr ; 9: 674414, 2021.
Article En | MEDLINE | ID: mdl-34307252

Background: The incidence of twin pregnancies has risen recently. Such pregnancies are associated with an increased risk for poor maternal and infant outcomes. Gestational weight gain, particularly in singleton pregnancies, has been well-linked with maternal and infant outcomes. The aim of the current meta-analysis was to evaluate the effects of gestational weight gain on maternal and fetal outcomes in women with twin pregnancies. Methods: A systematic search was conducted using the PubMed, Scopus, and Google Scholar databases. Studies, either retrospective or prospective in design, evaluating the effects of gestational weight gain (defined using Institute of Medicine (IOM) guidelines) maternal and/or fetal/neonatal outcomes in women with twin pregnancies were included. Statistical analysis was performed using STATA software. Results: Eleven studies were included in the meta-analysis. Mothers with inadequate weight gain had increased risk for gestational diabetes mellitus (OR 1.19; 95% CI: 1.01, 1.40) and decreased risk for gestational hypertension (OR 0.58; 95% CI: 0.49, 0.68) and cesarean section (OR 0.94; 95% CI: 0.93, 0.96). Neonates born to mothers with inadequate weight gain were susceptible to increased risk for preterm delivery (OR 1.17; 95% CI: 1.03, 1.34), very preterm delivery (gestational age <32 weeks) (OR 1.84; 95% CI: 1.36, 2.48), small for gestational age status (OR 1.41; 95% CI: 1.15, 1.72), low birth weight status (<2,500 g) (OR 1.27; 95% CI: 1.17, 1.38), and neonatal intensive care unit (NICU) admission (OR 1.16; 95% CI: 1.08, 1.24). The pooled findings indicate an increased risk for gestational hypertension (OR 1.82; 95% CI: 1.60, 2.06) and cesarean section (OR 1.07; 95% CI: 1.05, 1.08) among mothers with excessive weight gain. Neonates born to mothers with excessive weight gain were susceptible to increased risk for preterm delivery and very preterm delivery, but were associated with a decreased risk for low birth weight status and small for gestational age status. Conclusions: Gestational weight gain in twin pregnancy, either lower or higher than IOM recommended guidelines, is associated with poor maternal and neonatal outcomes. Our findings call for incorporating counseling on optimal weight gain during pregnancy as part of routine antenatal visits.

14.
Environ Res ; 200: 111732, 2021 09.
Article En | MEDLINE | ID: mdl-34324849

SO42-, a major component of acid mine drainage (AMD), plays an important role in study environment of AMD. We investigated the distribution and adsorption-desorption mechanisms of SO42- and the variation of stable isotope of sulfur (δ34S) values in the soil profile polluted by AMD. Results showed that the species and 34S values of SO42- differed significantly among different soil depths. In the surface soil (0-20 cm), native water-soluble SO42- (WSS) in the range ~85 % total SO42- was the dominant species. There was a peak of adsorption, which correlated significantly with amorphous oxide Fe, indicating that iron oxides and pH was fundamentally proportional to SO42- forms. The high concentrations of Cu2+ and Pb2+ also played important roles in form of SO42- in soil profile. Desorption kinetics of explained three SO42--bound forms. The trend mean δ34S values of WSS and AS in soil vertical profile was very similar with increasing from surface to subsurface, and have lower δ34S values than those of total sulfur, indicating that mineralization of organic sulfur should produce SO42- that was more depleted in δ34S. SO42- desorbed and trend δ34S values could provide reasonable explanation for the migration of SO42-. In the AMD irrigation scope, the higher SO42- concentration was reserved by immobilized as organic sulfur, and then main approach of SO42- migration was desorption and organic sulfur mineralize in now stage.


Soil Pollutants , Soil , Mining , Soil Pollutants/analysis , Sulfates , Sulfur
15.
Chemosphere ; 279: 130558, 2021 Sep.
Article En | MEDLINE | ID: mdl-33887596

Soil pollution, caused by heavy metals, is an environmental problem that requires an urgent solution in China. Chemical passivation is a technology that uses various passivators to reduce the availability of heavy metals in soil and realize the remediation of contaminated soil. In this study, we examined the effects of fly ash (FA), alkali-fused fly ash (AFFA), swine manure biochar (SB), and modifying biochar (MB) on the leachability of Cu, Zn, Pb, and Cd via soil culture experiments. The results showed that the addition of AFFA, SB, and MB significantly reduced the extractable contents of Cu, Pb, and Cd in the soil. AFFA and MB had the best passivation effect, followed by SB and FA. The passivation effect on Pb was the best, followed by that on Cu and Cd. AFFA modification significantly improved the passivation effect of MB on Cu, Pb, and Cd in composite contaminated soil. With the addition of 3% MB, the Pb, Cu, and Cd extracted by TCLP decreased by 95.7, 74.1, and 59.1%, respectively. Correlation analysis, Fourier transform infrared spectrometry, scanning electron microscopy, and energy-dispersive X-ray spectroscopy showed that the passivation mechanism is mainly due to an increase in the soil pH, silicate content, and cohesiveness. The soil culture experiments in this study proved that MB is a low-cost and highly efficient organic-inorganic composite passivator for multi-metal contaminated soils.


Metals, Heavy , Soil Pollutants , Alkalies , Animals , China , Coal Ash , Manure , Metals, Heavy/analysis , Soil , Soil Pollutants/analysis , Swine
16.
Biomed Res Int ; 2020: 2491304, 2020.
Article En | MEDLINE | ID: mdl-33150167

Gefitinib is a tyrosine kinase inhibitor of EGFR (epidermal growth factor receptor) and represents the first-line treatment for EGFR mutation patients with NSCLC (non-small-cell lung cancer) therapeutics. However, NSCLC patients are inclined to develop acquired gefitinib drug resistance through nowadays, unarticulated mechanisms of chemoresistance. Here, we investigated the role of TF (Trifolium flavonoids) on sensitizing gefitinib resistance in NSCLC cells and revealed its potential mechanism of action. We demonstrated that TF exerted significantly potential chemosensitivity in gefitinib resistant NSCLC cells. MTT assay and cytological methods were used to analyze cell viability and apoptosis in NSCLC cell line PC-9R. Both TF and gefitinib suppressed PC-9R cell growth in a dose-dependent manner. Subtoxic concentrations of TF did significantly augment gefitinib-induced apoptosis in PC-9R cell line. The TF promoted chemosensitivity was major mediated by the PARP and caspases activation. Meanwhile, the TF promoted chemosensitivity also decreased the expression of Bcl-2 and Mcl-1. Finally, TF significantly reduced the phosphorylation levels of STAT3 and ERK. Altogether, the results of the present study indicated the potential mechanisms of chemosensitivity of TF in gefitinib-induced apoptosis of NSCLC by downregulating ERK and STAT3 signaling pathways and Bcl2 and Mcl-1 expression and a promising application of TF in therapy of NSCLC with gefitinib resistant.


Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm/drug effects , Epithelial Cells/drug effects , Flavonoids/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Trifolium/chemistry , Apoptosis/drug effects , Apoptosis/genetics , Caspase 3/genetics , Caspase 3/metabolism , Caspase 8/genetics , Caspase 8/metabolism , Caspase 9/genetics , Caspase 9/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/genetics , Epithelial Cells/metabolism , Epithelial Cells/pathology , Flavonoids/isolation & purification , Gefitinib/pharmacology , Humans , Myeloid Cell Leukemia Sequence 1 Protein/genetics , Myeloid Cell Leukemia Sequence 1 Protein/metabolism , Poly(ADP-ribose) Polymerases/genetics , Poly(ADP-ribose) Polymerases/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction , bcl-2-Associated X Protein/genetics , bcl-2-Associated X Protein/metabolism
17.
J Alzheimers Dis ; 78(1): 277-290, 2020.
Article En | MEDLINE | ID: mdl-32986665

BACKGROUND: Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOEɛ4) is a risk factor for Alzheimer's disease (AD). OBJECTIVE: This study aimed to investigate the interactive role of androgen decline and APOEɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. METHODS: In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. RESULTS: The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH)were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOEɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. CONCLUSION: These results indicated that the interaction of androgen decline and APOEɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.


Alzheimer Disease/metabolism , Androgens/metabolism , Cognitive Dysfunction/metabolism , Gonadotropins/metabolism , Aged , Aged, 80 and over , Apolipoproteins E/metabolism , Biomarkers , China , Cognition , Dihydrotestosterone/metabolism , Disease Progression , Genotype , Humans , Male , Neuropsychological Tests , Testosterone/metabolism
18.
Sci Total Environ ; 729: 139055, 2020 Aug 10.
Article En | MEDLINE | ID: mdl-32388132

Two types of silica-composited biochars were prepared by mixing swine manure or rice straw with alkali-fused fly ash (AFFA) followed by pyrolysis. A 10% (w/w) AFFA modification improved the specific surface area, pore volume, and average pore size of the biochars. Certain surface oxygen-containing functional groups (i.e., -OH and CO) in the biochars were protected, and silicon-oxygen bonds (i.e., O-Si-O and OSi) were strengthened considerably by AFFA modifications during high-temperature pyrolysis. The adsorption capacity of biochar for methylene blue (MB) was enhanced after AFFA modification, and a modified biochar with the highest adsorption capacity was prepared at a pyrolysis temperature of 700 °C, pyrolysis holding time of 2 h, and an AFFA proportion of 10%. The MB adsorption capacity of the modified biochars significantly increased when the pH of the solution increased (from 3 to 13). The adsorption data were well described by a pseudo-second-order model and Langmuir isotherms. The maximum MB adsorption capacities of the modified swine manure and rice straw biochars were 143.76 mg/g and 131.58 mg/g, respectively. The adsorption capacities of the AFFA-modified biochars were 10.7-112.3% higher than those of the unmodified biochars. The enhanced MB adsorption capacities of the former appear to be attributed to their increased specific surface areas, increased porosities, strong oxygen-containing functional groups, and high contents of exchangeable sodium ions. These results indicate that industrial and agricultural wastes can be reused to produce novel silica-composited biochars with high MB removal capacity. Accordingly, these biochars could be effectively used to treat wastewater and thus to mitigate solid waste disposal-related problems.


Coal Ash , Adsorption , Alkalies , Animals , Charcoal , Methylene Blue , Silicon Dioxide , Swine
19.
Environ Res ; 186: 109490, 2020 07.
Article En | MEDLINE | ID: mdl-32302871

In acid mine drainage (AMD) polluted rivers, considerable fraction of potential toxic elements are temporarily sequestered by sediments. There are two main potential environmental hazards associated with the sediments, acidity liberation and re-mobilization of metallic elements, during environmental conditions change. The effects of AMD standstill and water dilution on metallic elements migration were assessed in an AMD standstill test and a dialysis experiment. Maintaining AMD standstill, often occurring in AMD damming process, could induce the occurrence of iron secondary minerals precipitation along with attenuation of dissolved elements and a decrease in water pH value. Both field sediments and lab precipitates were confirmed as being dominant with schwertmannite which was the most important source and sink for acidity and metallic elements. The mechanism of cation heavy metals scavenging implied by FTIR results mostly depended on the exchanging of H+ from surface hydroxyl groups (-OH) in schwertmannite-rich sediments. For arsenic oxyanion, its adsorption included surface complexation with iron hydroxyl groups at the mineral surface, as well as anion exchange of SO42- present in the structure. The quantities of acidity release differed significantly from 20 to 3714 mol H+/t depending on the iron hydroxyl minerals type and their contents in the corresponding sediments in 35 d dialysis, with the release rate well fitted by the second order model. Slight degree of phase transformation in schwertmannite dominant sediment had resulted in a high risk of metallic element release during the 35 d dilution duration. The significant risk of metallic elements release was ranked in the order of Cd > Mn > Zn > Pb, and with more than 89% of Cd released from FS6 and 82% from LPS1. Relatively, Cu and As in sediments were much more stable. Overall, damming was an effective and low cost pretreatment strategy for AMD pollution control. Knowledge of the characteristics of iron secondary minerals in river sediments is essential premise for both comprehensive assessment of site contamination status and effective remediation strategy decision.


Metals, Heavy , Water Pollutants, Chemical , Environmental Monitoring , Geologic Sediments , Metals, Heavy/analysis , Minerals/analysis , Mining , Rivers , Water Pollutants, Chemical/analysis
20.
Sci Total Environ ; 701: 134916, 2020 Jan 20.
Article En | MEDLINE | ID: mdl-31726407

A national-scale survey was conducted to assess the levels and distribution of two extensively used pesticides (pyrethroids and atrazine) in greenhouse and open-field soils in 20 provinces across China. Concentrations between 1.30 and 113 ng/g and 0.51-85.4 ng/g for the total pyrethroids (PYs) and of LOD-137 ng/g and LOD-134 ng/g for atrazine were found in greenhouse and open-field soils, respectively. Higher contaminations were found in the greenhouse than in the open fields. The levels of total pyrethroids in 80% of the greenhouses and of atrazine in 60% of the greenhouses were significantly higher than those in the nearby open-field soils (p < 0.05), respectively. The contamination of PYs and atrazine was generally more serious in the northern provinces of China, such as Heilongjiang, Jilin, Liaoning, Beijing, and Hebei. Pearson correlation analysis revealed that the contamination of PYs was significantly correlated with the soil total organic carbon (TOC) value in both greenhouse and open-field soils. Canonical correspondence analysis (CCA) showed that PYs might have an impact on the microbial alpha diversity, while cyhalothrin and cypermethrin may be the key factors affecting the microbial community in the greenhouse and open-field soils. The soil samples containing pesticide residues showed distinct taxonomic and functional communities, where an increased diversity and abundance of microorganisms able to degrade pesticides was observed with high-level PYs contamination. These findings provide useful information for evaluating PYs and atrazine pollution and for contamination management in greenhouse agriculture.


Atrazine/analysis , Environmental Monitoring , Pesticides/analysis , Pyrethrins/analysis , Soil Pollutants/analysis , Agriculture , China , Pesticide Residues/analysis , Soil/chemistry
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