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1.
Sci Total Environ ; 784: 147106, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34088062

RESUMO

Fine particle matter (PM2.5) is recognized as atrial fibrillation (AF) risk factor, especially for older adults. However, studies on the relationship between PM2.5 and AF were inconsistent. Herein, we present a systematic review to further assess the correlation between PM2.5 and AF in older adults (average age > 50 years old). A comprehensive search was conducted with the keywords in PubMed (675 records), Web of Science (1130 records), Embase (82 records), and the Cochrane Library (42 records). Using Stata12.0 software to test the heterogeneity between studies, and select the corresponding model to calculate the comprehensive effect value, odds ratio (OR, odds ratio), the pooled %-change (percentage change) and its 95% confidence interval (CL, confidence interval). A total of 16 observational studies were included, involving 10,580,394 participants, the results showed that PM2.5 had an adverse effects on AF in older adults. An association was found between exposure to PM2.5 (per 10 µg/m3 increase) and AF in older adults, with the corresponding pooled OR (1.11, 95% CI: 1.03-1.19) and pooled %-change (1.01%, 95% CI: 0.14%-1.88%). Our study indicated that PM2.5 exposure was significantly related to increased incidence of AF in older adults. Both the pooled OR and %-change value were higher in areas with higher levels of PM2.5(≥25 µg/m3).

2.
Bioengineered ; 12(1): 1752-1765, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33975518

RESUMO

Most cases of endometrial adenocarcinoma (EAC) are diagnosed early and have a good prognosis; however, grade 3 (G3) EACs have poor outcomes. We retrospectively analyzed the data of 11,519 patients with G3 EACs registered between 2004 and 2015 in the Surveillance, Epidemiology, and End Results Program database and constructed a nomogram to guide clinicians in decision-making and accurate prediction of the prognosis. The caret package was used to divide samples into a training set and a validation set. Univariate and multivariate Cox regression analyses were performed, and a nomogram was constructed. A calibration curve was plotted, and a decision curve analysis was performed to verify the accuracy and clinical utility in both cohorts. The Cox regression analysis revealed that age, race, tumor size, number of lymph nodes resected, International Federation of Gynecology and Obstetrics stage, tumor/node stage, and adjuvant therapy were the prognostic factors for G3 EAC, and these were included in the nomogram. The area under the curve values of the training cohort for 1-, 3-, and 5-year were 0.832, 0.798, and 0.784, respectively for the overall survival (OS) group, and 0.858, 0.812, and 0.799, respectively for the cancer specific survival (CSS) group. A nomogram was constructed to predict the survival rate of patients with G3 EACs more accurately. The predictive nomogram will help clinicians manage patients with G3 EACs more effectively in terms of clinical prognosis.

3.
Nanotoxicology ; : 1-15, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941019

RESUMO

Ambient air pollution is a leading cause of non-communicable disease in the world. PM2.5 has the potential to change the miRNAs profiles, which in turn causes cardiovascular effects. Hypoxia-inducible factor (HIF)-1 plays a critical role in the development of atherosclerosis. Yet, the possible role of miR-939-5p/HIF-1α in PM2.5-induced endothelial injury remains elusive. Therefore, the study aims to investigate the effects of miR-939-5p and HIF-1α on PM2.5-triggered endothelial injury. The results from immunofluorescence, qRT-PCR, LSCM, and western blot assays demonstrated that PM2.5 increased the levels of HIF-1α, inflammation and apoptosis in human aortic endothelial cells (HAECs). Yet, the inflammatory response and mitochondrial-mediated apoptosis pathway were effectively inhibited in HIF-1α knockdown HAECs lines. The expression of miR-939-5p was significantly down-regulated in HAECs after exposed to PM2.5. The luciferase reporter, qRT-PCR and western blot results demonstrated that miR-939-5p could directly targeted HIF-1α. And the miR-939-5p overexpression restricted PM2.5-triggered decreases in cell viability and increases in lactic dehydrogenase (LDH) activity, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and inflammation. In addition, miR-939-5p overexpression remarkably suppressed PM2.5-triggered BcL-2/Bax ratio reduction and Cytochrome C, Cleaved Caspase-9 and Cleaved Caspase-3 expression increase, revealed that miR-939-5p hampered PM2.5-induced endothelial apoptosis through mitochondrial-mediated apoptosis pathway. Our results demonstrated that PM2.5 increased the expression of HIF-1α followed by a pro-inflammatory and apoptotic response in HAECs. The protective effect of miR-939-5p on PM2.5-triggered endothelial cell injury by negatively regulating HIF-1α. miR-939-5p might present a new therapeutic target for PM2.5 induced endothelial injury.

4.
Int J Oncol ; 58(6)2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955519

RESUMO

Kidins220 is a transmembrane scaffold protein involved in several types of cancer. The aim of the present study was to examine the role of Kidins220 in tumorigenesis and disease progression of pancreatic cancer. The relevant signalling pathways including EGFR, EMT, and MMP were also investigated. The expression of Kidins220 was examined at the transcript and protein level. The Kidins220 knockdown cell model was established and its influence on cellular functions was determined. Involvement of Kidins220 in tumorigenesis and metastasis was examined in CD1 mice, respectively. The results showed that, reduced Kidin220 expression was associated with tumorigenesis, metastasis, and overall survival of pancreatic cancer. Knockdown of Kidins220 promoted proliferation, colony formation and tumorigenic capacity of pancreatic cancer cells in vitro and in vivo, respectively. Kidins220 regulated pancreatic cancer cell migration through the EGFR/AKT/ERK signalling pathway. Furthermore, enhanced EMT was observed in the pancreatic cancer cell lines with the knockdown of Kidins220, underlying EGFR regulation. Kidins220 also affected cell invasion via MMP1. A reduced expression of Kidins220 was observed in pancreatic cancer, which is associated with disease progression, distant metastasis and poor prognosis. The loss of Kidins220 in pancreatic cancer may contribute to disease progression through the upregulation of EGFR and downstream signalling.

5.
Environ Pollut ; 284: 117446, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34058501

RESUMO

Researches have shown that silica nanoparticles (SiNPs) could reduce both the quantity and quality of sperm. However, the mechanism of toxicity induced by SiNPs in the male reproductive system is still unclear. In this study, male mice were randomly divided into a control group, and SiNPs treated group (20 mg/kg dose; n = 30 per group). Half of the mice per group were sacrificed on 35 days and the remaining on 50 days of the SiNPs exposure. SiNPs were found to decrease sperm count and mobility, increase the sperm abnormality rate, and damage the testes' structure. Furthermore, SiNPs decreased the protein levels of Protamine 1(PRM1) and elevated the histones' levels and suppressed the chromatin condensation of sperm. There was a significant reduction of the ubiquitinated H2A (ubH2A)/H2B (ubH2B) and RING finger protein 8 (RNF8) levels in the spermatid nucleus, while the RNF8 level in the spermatid cytoplasm increased evidently. The protein expression levels of PIWI-like protein 1(MIWI) in the late spermatids significantly increased on day 35 of SiNPs exposure. After 15 days of the withdrawal, the sperm parameters and protamine levels, and histones in the epididymal sperm were unrecovered; however, the changes in testis induced by SiNPs were recovered. Our results suggested that SiNPs could decrease the RNF8 level in the nucleus of spermatid either by upregulating of the expression of MIWI or by inhibiting its degradation. This resulted in the detention of RNF8 in the cytoplasm that maybe inhibited the RNF8-mediated ubiquitination of ubH2A and ubH2B. These events culminated in creating obstacles during the H2A and H2B removal and chromatin condensation, thereby suppressing the differentiation of round spermatids and chromatin remodeling, which compromised the sperm quality and quantity.

6.
FEBS Open Bio ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051059

RESUMO

Mitophagy, a form of autophagy, plays a role in cancer development, progression and recurrence. Cancer stem cells (CSCs) also play a key role in these processes, but it is unknown whether mitophagy can regulate the stemness of CSCs. Here, we employed the A549-SD human non-small cell lung adenocarcinoma CSC model that we have developed and characterized to investigate the effect of mitophagy on the stemness of CSCs. We observed a positive relationship between mitophagic activity and the stemness of lung CSCs. At the mechanistic level, our results suggest that augmentation of mitophagy in lung CSCs can be induced by FIS1 through mitochondrial fission. In addition, we assessed the clinical relevance of FIS1 in lung adenocarcinoma by using the TCGA database. An elevation in FIS1, when observed together with other prognostic markers for lung cancer progression, was found to correlate with shorter overall survival.

7.
Sci Total Environ ; 787: 147604, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33992945

RESUMO

The in-utero environmental exposure to fine particulate matter (PM2.5) might lead to adverse birth outcomes, such as low birth weight (LBW) and preterm birth (PTB), thereby increasing susceptibility to diseases in later life. However, no studies have examined the underlying mechanism through cross-omics of lipidome and adipokines profiling, as well as the possible effect modification by maternal hyperlipidemia. In total, 203 mother-newborn pairs were recruited in the birth cohort study ongoing since February 2017 in Beijing, China. Individual-level of PM2.5 exposure was estimated using a satellite data based random forest model. Cord blood lipidome and adipokines were assessed through the lipidomic approaches and antibody-based array. Multivariable logistic/linear regression models and moderation analysis were employed in this study. We observed a significantly increased risk of PTB associated with PM2.5 exposure during the second trimester, especially in pregnant women with pre-existing hyperlipidemia. 9 lipid classes and 21 adipokines were associated with PM2.5 exposure independently or significantly influenced by the interaction of maternal PM2.5 exposure and hyperlipidemia. In addition, 4 adipokines (ANGPTL4, IGFBP-2, IL-12p40, and TNF-RII) and 3 lipid classes [phosphatidylcholines (PCs), phosphatidylinositols (PIs), and triglycerides (TGs)] were related to the increased risk of PTB, indicating that inflammation, IGF/IGFBP axis, and lipolysis induced lipid homeostasis disorder of PCs, TGs, and PIs might be the possible mediators for the PM2.5-induced adverse birth outcomes. Our results substantiated the need for reducing exposure in susceptible populations.

8.
Biomaterials ; 274: 120873, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33989972

RESUMO

Exosomes and their internal components have been proven to play critical roles in cell-cell interactions and intrinsic cellular regulations, showing promising prospects in both biomedical and clinical fields. Although conventional methods have so far been utilized to great effect, accurate bioanalysis remains a major challenge. In recent years, the fast-paced development of nanomaterials with unique physiochemical properties has led to a boom in the potential bioapplications of such materials. In particular, the application of nanomaterials in exosome bioanalysis provides a great opportunity to overcome the current challenges and limitations of conventional methods. A timely review of the research progress in this field is thus of great significance to the continued development of new methods. This review outlines the properties and potential uses of exosomes, and discusses the conventional methods currently used for their analysis. We then focus on exploring the current state of the art regarding the use of nanomaterials for the isolation, detection and even the subsequent profiling of exosomes. The main methods are based on principles including fluorescence, surface-enhanced Raman spectroscopy, colorimetry, electrochemistry, and surface plasmon resonance. Additionally, research on exosome-based nanomaterials tumor therapy is also promising from a clinical perspective, so the research progress in this branch is also summarized. Finally, we look at ways in which the field might develop in the future.

9.
Environ Pollut ; 277: 116771, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652185

RESUMO

Silica nanoparticles (SiNPs) could cause reproductive toxicity. The role of miRNAs in reproductive toxicity induced by SiNPs is still ambiguous. The present study was designed to investigate the role of miRNA-450 b-3p. In vivo, 40 male mice were randomly divided into control, and 20 mg/kg SiNPs groups. The mice were administrated by tracheal perfusion for 35 days. In vitro, spermatocyte cells (GC-2spd cells) were divided into 6 groups: 0 µg/mL SiNPs groups, 5 µg/mL SiNPs groups, 5 µg/mL SiNPs + miRNA-450 b-3p mimic transfection group, 5 µg/mL SiNPs + miRNA-450 b-3p mimic negative control group, 5 µg/mL SiNPs + miRNA-450 b-3p inhibitor transfection group, and 5 µg/mL SiNPs + miRNA-450 b-3p inhibitor negative control group. The results showed that SiNPs induced the apoptosis of spermatogenic cells, decreased the quantity and quality of the sperm, reduced the expressions of miR-450 b-3p, and increased the protein expressions of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, and Caspase-3 in the testis. In vitro, the mimic of miRNA-450 b-3p reversed the decrease of viability and the increase of apoptosis rate and significantly antagonized the expression enhancements of the MTCH2, BID, BAX, Cytochrome C, Caspase-9, Caspase-3 induced by SiNPs, while inhibitor of miRNA-450 b-3p further promoted the effects induced by SiNPs. The result suggested that SiNPs could inhibit the miR-450 b-3p expression resulting in activation of the mitochondrial apoptosis signaling pathways by regulating the MTCH2 in the spermatocyte cells and, thus, induce the reproductive toxicity.


Assuntos
MicroRNAs , Nanopartículas , Animais , Apoptose , Masculino , Camundongos , MicroRNAs/genética , Proteínas de Transporte da Membrana Mitocondrial , Nanopartículas/toxicidade , Dióxido de Silício/toxicidade , Espermatócitos
10.
Chemosphere ; 275: 129969, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33662726

RESUMO

Quantities of researches have demonstrated silica nanoparticles (SiNPs) exposure inevitably induced damage to respiratory system, nonetheless, knowledge of its toxicological behavior and metabolic interactions with the cellular machinery that determines the potentially deleterious outcomes are limited and poorly elucidated. Here, the metabolic responses of lung bronchial epithelial cells (BEAS-2B) under SiNPs exposure were investigated using ultra performance liquid chromatography-mass spectrum (UPLC-MS)-based metabolomics research. Results revealed that even with low cytotoxicity, SiNPs disturbed global metabolism. Five metabolic pathways were significantly perturbed, in particular, oxidative stress- and mitochondrial dysfunction-related GSH metabolism and pantothenate and coenzyme A (CoA) biosynthesis, where the identified metabolites glutathione (GSH), glycine, beta-alanine, cysteine, cysteinyl-glycine and pantothenic acid were included. In support of the metabolomics profiling, SiNPs caused abnormality in mitochondrial structure and mitochondrial dysfunction, as evidenced by the inhibition of cellular respiration and ATP production. Moreover, SiNPs triggered oxidative stress as confirmed by the dose-dependent ROS generation, down-regulated nuclear factor erythroid 2-related factor 2 (NRF2) signaling, together with GSH depletion in SiNPs-treated BEAS-2B cells. Oxidative DNA damage and cell membrane dis-integrity were also detected in response to SiNPs exposure, which was correspondingly in agreed with the elevated 8-hydroxyguanosine (8-OHdG) and decreased phospholipids screened through metabolic analysis. Thereby, we successfully used the metabolomics approaches to manifest SiNPs-elicited toxicity through oxidative stress, mitochondrial dysfunction, DNA damage and rupture of membrane integrity in BEAS-2B cells. Overall, our study provided novel insights into the mechanism underlying SiNPs-induced pulmonary toxicity.


Assuntos
Nanopartículas , Dióxido de Silício , Cromatografia Líquida , Células Epiteliais/metabolismo , Pulmão , Metabolômica , Mitocôndrias/metabolismo , Nanopartículas/toxicidade , Estresse Oxidativo , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Espectrometria de Massas em Tandem
11.
Future Oncol ; 17(18): 2351-2363, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33709789

RESUMO

Background: Chemotherapy-related adverse events may restrain taxane/cisplatin administration as a regimen for patients with esophageal squamous cell carcinoma. Genetic polymorphisms may contribute to adverse event susceptibility. Method & results: The authors genotyped ten SNPs from five genes (rs1045642, rs2032582 and rs3213619 of ABCB1; rs2231137 and rs2231142 of ABCG2; rs246221 of ABCC1; rs3740066 of ABCC2; and rs10771973, rs12296975 and rs1239829 of FGD4) in 219 patients with esophageal squamous cell carcinoma treated with taxane/cisplatin. Patients with severe toxicities were compared with those with minor or no adverse events by unconditional logistic regression models and semi-Bayesian shrinkage. After adjustment for age and sex, with the null prior, FGD4 rs1239829 was statistically significantly related to grade 3-4 leukopenia (odds ratio [95% CI] in dominant model = 1.77 [1.04-3.03]). Conclusion: The minor allele of FGD4 rs1239829 was related to grade 3-4 leukopenia in patients with esophageal squamous cell carcinoma treated with taxane/cisplatin, with unclear biological mechanism.

12.
J Hazard Mater ; 414: 125504, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33652219

RESUMO

Many studies have linked airborne fine particulate matter (PM2.5) exposure to cardiovascular diseases. We performed a time-series analysis to investigate whether the disruption of lipid metabolism recovered or lasted after acute PM2.5 exposure in mice. Targeted lipidomic analysis showed that four major plasma membrane phospholipids along with cholesterol esters (CE) were significantly altered on 7th post-exposure day (PED7), and the alteration reached a peak on PED14. On PED21, the phosphatidylcholine (PC) decrease was more marked than on PED14, and its resurgence was indirectly linked to triglyceride (TG) increase. Homocysteine (HCY), lactate dehydrogenase (LDH), and α-hydroxybutyrate dehydrogenase (α-HBDH) levels increased but glucose levels decreased markedly in a dose- and time-dependent manner throughout the experimental period. Network analysis showed that the lasting lipid deregulation on PED21 correlated to myocardial markers and glucose interruption, during which high-density lipoprotein cholesterol (HDL-C) decreased. The present data implied that the constructional membrane lipids were initially interrupted by PM2.5, and the subsequent rehabilitation resulted in the deregulation of storage lipids; the parallel myocardial and glucose effects may be enhanced by the lasting HDL-C lipid deregulation on PED21. These myocardial and lipidomic events were early indicators of cardiovascular risk, resulting from subsequent exposure to and accumulation of PM2.5.


Assuntos
Poluentes Atmosféricos , Material Particulado , Poluentes Atmosféricos/análise , Animais , Biomarcadores , Metabolismo dos Lipídeos , Lipidômica , Lipídeos , Masculino , Camundongos , Material Particulado/análise , Material Particulado/toxicidade
13.
Environ Pollut ; 277: 116726, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33639598

RESUMO

Fine particulate matter (PM2.5) and ozone (O3) air pollution can cause abnormal changes in blood pressure (BP), blood glucose and lipids, which are important indicators for cardiovascular health. Psychosocial stress could be a potential effect modifier for adverse health effects of air pollution, but research evidence is scarce. A cross-sectional study with 373 elderly subjects was conducted in Beijing during 2018-2019. We collected psychosocial stress information on anxiety, perceived stress and depression, obtained daily environmental data, measured resting BP, blood glucose and lipids in study participants, and analyzed the associations of PM2.5 or O3 with cardiovascular health indicators and the modification effect by psychosocial stress. Results showed that PM2.5 was significantly associated with increased systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) ; and O3 was significantly associated with elevated DBP, glycated hemoglobin (HbA1c) and total triglyceride (TG). In addition, the associations of PM2.5 with TG, and O3 with SBP and TG were higher in participants with high psychosocial stress, whereas the associations of O3 with high-density lipoprotein cholesterol (HDL-C) were higher in participants with low psychosocial stress. For an interquartile range (IQR) (56.8 µg/m³) increase in PM2.5 at 4-d moving average, TG increased by 21.43% (95% CI: 2.90, 43.29) in high perceived-stress group, and decreased by 20.05% (95% CI: -30.31, -8.28) in low perceived-stress group (p for interaction = 0.04). For an IQR (63.0 µg/m³) increase in O3 at 2-d moving average, TG increased by 32.01% (95% CI: 7.65, 61.89) in high perceived-stress group, and increased by 7.95% (95% CI: -9.80, 29.20) only in low perceived-stress group (p for interaction = 0.04). For an IQR (64.0 µg/m³) increase in O3 at 3-d moving average, HDL-C decreased by 4.55% (95% CI: -12.15, 3.72) in high perceived-stress group, and increased by 0.57% (95% CI: -6.99, 8.75) in low perceived-stress group (p for interaction=0.002). In conclusion, our results indicated that short-term exposures to PM2.5 and O3 were associated with significant changes in BP, blood glucose and lipids, and psychosocial stress may increase the susceptibility of the participants to the adverse cardiovascular effects of PM2.5 and O3.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Ozônio , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Pequim , Estudos Transversais , Exposição Ambiental/efeitos adversos , Humanos , Ozônio/análise , Material Particulado/análise , Estresse Psicológico
14.
Anal Chem ; 93(7): 3426-3435, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33569949

RESUMO

Phagocyte respiratory burst in immune responses generates enormous amounts of reactive oxygen species (ROS) to fulfill primary defense against neoplasia. However, the beneficial functions associated with ROS, especially the potent oxidant/nucleophile peroxynitrite, in an immunological process are still ambiguous. Herein, we report the construction and biological assessment of cyanine-based fluorescent biosensors, which are based on a nonoxidative strategy for peroxynitrite detection. The established nonoxidative strategy is composed of nucleophilic substitution and nanoaggregate formation initiated by peroxynitrite. The proposed nonoxidative strategy in this study could maintain cellular oxidative stress in the critical process of detection and preserve homeostasis of cell metabolism. The remarkable detection sensitivity, reaction selectivity, and spectral photostability of our biosensors enabled us to visualize endogenous peroxynitrite levels in immune-stimulated phagocytes. With the aid of basal peroxynitrite imaging in an acute peritonitis model, the visualization of peroxynitrite level variations in immune responses of tumorigenesis was accomplished assisted by our biosensors. It is envisioned that our strategy provides a promising tool for early tumor diagnosis and evaluation of tumor suppression in the process of immune responses without disturbing the functions of ROS signaling transduction.

15.
Chin J Integr Med ; 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33609233

RESUMO

OBJECTIVE: To compare the therapeutic effect of different animal bile powders on lipid metabolism disorders induced by high-fat diet in rats, and analyze the bioactive components of each animal bile powder. METHODS: Sixty Sprague-Dawley rats were randomly divided into 6 groups (n=10): normal diet control group, high-fat diet model group, high-fat diet groups orally treated with bear, pig, cow and chicken bile powders, respectively. Serum biochemical markers from the abdominal aorta in each group were analyzed. Changes in the body weight and liver weight were recorded. Pathohistological changes in the livers were examined. High performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was used to determine the composition of bioactive components in each animal bile powder. RESULTS: Treatment with different types of animal bile powders had different inhibitory effects on high-fat diet-induced increase of body weight and/or liver weight in rats, most notably in bear and pig bile powders (P<0.05). High-fat diet induced lipid metabolism disorder in rats, which could be reversed by treatment with all kinds of bile powders. Bear bile and chicken bile showed the most potent therapeutic effect against lipid metabolism disorder. Cow and bear bile effectively alleviated high-fat diet induced liver enlargement and discoloration, hepatocyte swelling, infiltration of inflammatory cells and formation of lipid vacuoles. Bioactive component analysis revealed that there were significant differences in the relative content of taurocholic acid, taurodeoxycholic acid and ursodeoxycholic acid among different types of animal bile. Interestingly, a unique component with molecular weight of 496.2738 Da, whose function has not yet been reported, was identified only in bear bile powder. CONCLUSIONS: Different animal bile powders had varying therapeutic effect against lipid metabolism disorders induced by high-fat diet, and bear bile powder demonstrated the most effective benefits. Bioactive compositions were different in different types of animal bile with a novel compound identified only in bear bile powder.

16.
ACS Sens ; 6(3): 852-862, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33555177

RESUMO

Exosomal microRNAs (miRNAs) have been proved to be important biomarkers for the early diagnosis of cancers. However, the accurate quantification of exosomal miRNAs is hampered either by laborious exosome isolation and lysis or by RNA extraction and the amplification process. Here, we reported an in situ platform for direct exosomal miRNAs from serum samples. First, locked nucleic acid (LNA)-modified Au@DTNB (DTNB is the Raman reporter molecule 5,5'-dithiobis-(2-nitrobenzoic acid)) was synthesized as surface-enhanced Raman scattering (SERS) tags to enter into exosomes and assemble with target miRNAs to induce hot-spot SERS signals. Second, Fe3O4@TiO2 nanoparticles were added to enrich the exosomes through affinity interaction of the TiO2 shell for further SERS detection. Based on the platform, target miRNAs can be directly qualified in situ with a detection limit of 0.21 fM, which is better or comparable with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and other in situ methods reported before. Moreover, neither capture antibody nor ultracentrifugation pretreatment was needed in the whole detection procedure. Using exosomal miRNA-10b as a proof of concept, pancreatic ductal adenocarcinoma (PDAC) patients can be recognized from normal controls (NCs) with an accuracy of 99.6%. The simple and sensitive in situ exosomal miRNA detection assay can be seen as a noninvasive liquid biopsy assay for clinical cancer diagnostic adaption.


Assuntos
Exossomos , MicroRNAs , Humanos , MicroRNAs/genética , Análise Espectral Raman , Titânio
17.
BMC Urol ; 21(1): 22, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568095

RESUMO

BACKGROUND: Ureteral fibro-epithelial polyp (UFP) is a rare benign ureteral tumor, and surgical removal of the polyps is still the preferred solution. Although many cases have reported polyps extending to the bladder, our case was the first to report a huge UFP that underwent endoscopic laser resection to highlight the urethra and cause severe end hematuria permanently. CASE PRESENTATION: In 2019, a 37-year-old woman came to the hospital because of hematuria and a dark red extraurethral mass. CTU inspection showed: filling defect between the right ureter and the bladder at the entrance of the bladder. After ureteroscopy, it was found that the ureteral mass came out of the urethral orifice. Then, under the direct view of the ureteroscope, a Ho:YAG laser was used to remove the tumor by cutting off along the its base, and the patient was discharged 3 days after the operation. CONCLUSION: Urethral polyps from the ureter should be considered in the differential diagnosis of urethral neoplasms. Ho:YAG laser resection under ureteroscopy is an effective option for treating UFP, but be careful of ureteral stricture after surgery.

18.
Cell Death Dis ; 12(1): 98, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468994

RESUMO

It has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.

19.
Environ Int ; 146: 106307, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395949

RESUMO

Decabrominated diphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) are common flame retardants utilized in many kinds of electronic and textile products. Due to their persistence and bioaccumulation, BDE-209 and DBDPE extensively exist in the surrounding environment and wild animals. Previous studies have indicated that BDE-209 could induce male reproductive toxicity, whereas those of DBDPE remains relatively rare. In this study, we investigated the effects of both BDE-209 and DBDPE on reproductive system in male SD rats, and explored the potential mechanisms under the reproductive toxicity of BDE-209 and DBDPE. Male rats were orally administered with BDE-209 and DBDPE (0, 5, 50 and 500 mg/kg/day) for a 28-day exposure experiment. The current results showed that BDE-209 and DBDPE led to testicular damage in physiological structure, decreased the sperm number and motility, and increased the sperm malformation rates in rat. Moreover, BDE-209 and DBDPE could damage the telomeric function by shortening telomere length and reducing telomerase activity, which consequently caused cell senescence and apoptosis in testis of rat. This could contribute to the decline of sperm quality and quantity. In conclusion, BDE-209 and DBDPE led to reproductive toxicity by inducing telomere dysfunction and the related cell senescence and apoptosis in testis of SD rat. Comparatively, BDE-209 had more severe effects on male reproduction. Our findings may provide new insight into the potential deleterious effects of BFRs on male reproductive health.


Assuntos
Bromobenzenos , Retardadores de Chama , Animais , Apoptose , Senescência Celular , Retardadores de Chama/toxicidade , Éteres Difenil Halogenados/toxicidade , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Reprodução , Telômero
20.
Environ Int ; 147: 106341, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33383389

RESUMO

BACKGROUND: Oxidative stress has been suggested to be one of the key drivers of health impact of particulate matter (PM). More studies on the oxidative potential of PM alone, but fewer studies have comprehensively evaluated the effects of external and internal exposure to PM compositions on oxidative stress in population. OBJECTIVE: To comprehensively investigate the exposure-response relationship between PM and its main compositions with oxidative stress indicators. METHODS: We conducted a cross-sectional study including 768 participants exposed to particulates. Environmental levels of fine particulate matter (PM2.5), polycyclic aromatic hydrocarbons (PAHs) and metals in PM were measured, and urinary levels of PAHs metabolites and metals were measured as internal dose, respectively. Multivariable linear regression models were used to analyze the correlations of PM exposure and urinary levels of 8-hydroxy-2́'-deoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and malondialdehyde (MDA). RESULTS: The concentration of both PM2.5 and total PAHs was significantly correlated with increased urinary 8-OHdG, 8-iso-PGF2α and MDA levels (all p < 0.05). The levels of 4 essential metals all showed significant exposure-response increase in urinary 8-OHdG in both current and non-current smokers (all p < 0.05); ambient selenium, cobalt and zinc were found to be significantly correlated with urinary 8-iso-PGF2α (p = 0.002, 0.003, 0.01, respectively); only selenium and cobalt were significantly correlated with urinary MDA (p < 0.001, 0.01, respectively). Furthermore, we found each one-unit increase in urinary total OH-PAHs generated a 0.32 increase in urinary 8-OHdG, a 0.22 increase in urinary 8-iso-PGF2α and a 0.19 increase in urinary MDA (all p < 0.001). Furthermore, it was found that the level of 12 urinary metals all showed significant and positive correlations with three oxidative stress biomarkers in all subjects (all p < 0.001). CONCLUSIONS: Our systematic molecular epidemiological study showed that particulate matter components could induce increased oxidative stress on DNA and lipid. It may be more important to monitor and control the harmful compositions in PM rather than overall particulate mass.


Assuntos
Material Particulado , Hidrocarbonetos Policíclicos Aromáticos , 8-Hidroxi-2'-Desoxiguanosina , Biomarcadores , Estudos Transversais , Desoxiguanosina , Humanos , Estresse Oxidativo , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
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