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1.
Chin J Dent Res ; 22(3): 157-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508603

RESUMO

OBJECTIVE: To evaluate the therapeutic effect of local injection of stem cells from human exfoliated primary teeth (SHED) on periodontitis in mice. METHODS: Fifteen female mice were randomly divided into three groups: normal control group, periodontitis group and SHED treatment group. A periodontitis model was established by ligating a 0.2 mm orthodontic ligation wire to the maxillary first molar. The SHED group was injected with SHED at 3 weeks post-ligation. All mice were sacrificed and their maxillae were dissected five weeks post-ligation. Clinical assessments, micro-computed tomography (micro-CT) scanning, and histologic examination were used to evaluate the outcome of tissue regeneration. RESULTS: Micro-CT analysis showed that SHED administration significantly increased periodontal regeneration and decreased the distance between the cemento-enamel junction and the alveolar bone crest. In addition, histopathological photomicrographs showed new regenerated bone, the number of TNF-α-positive, IFN-γ-positive and CD4+ cells decreased, and osteoclasts-positive decreased in the periodontal defect area in the SHED group compared with the periodontitis group. CONCLUSION: SHED administration suppresses the expression of inflammatory factors, inhibits the production of osteoclasts, and promotes the regeneration of periodontal tissues.

2.
Redox Biol ; 26: 101295, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31421410

RESUMO

Hypertension is one of the major predisposing factors for neurodegenerative disease characterized with activated renin-angiotensin system (RAS) in both periphery and brain. Vitamin D (VitD) is recently recognized as a pleiotropic hormone with strong neuroprotective properties. While multiple lines of evidence suggest that VitD can act on RAS, the evidence concerning the crosstalk between VitD and RAS in the brain is limited. Therefore, this study aims to evaluate whether VitD can modulate brain RAS to trigger neuroprotective actions in the brain of spontaneously hypertensive rats (SHR). Our data showed that calcitriol treatment induced VDR expression and inhibited neural death in the prefrontal cortex of SHR. Sustained calcitriol administration also inhibited microglia M1 polarization, but enhanced M2 polarization, accompanied with decreased expression of proinflammatory cytokines. We then further explored the potential mechanisms and showed that SHR exhibited overactivated classical RAS with increased expression of angiotensin II (Ang II) receptor type 1 (AT1), angiotensin converting enzyme (ACE) and Ang II production, whereas the counteracting arm of traditional RAS, ACE2/Ang(1-7)/MasR, was impaired in the SHR brain. Calcitriol nonsignificantly suppressed AT1 and ACE but markedly reduced Ang II formation. Intriguingly, calcitriol exerted pronouncedly impact on ACE2/Ang(1-7)/MasR axis with enhanced expression of ACE2, MasR and Ang(1-7) generation. Meanwhile, calcitriol ameliorated the overactivation of NADPH-oxidase (Nox), the downstream of RAS, in SHR, and also mitigated oxidative stress. In microglial (BV2) cells, we further found that calcitriol induced ACE2 and MasR with no significant impact on ACE and AT1. In accordance, calcitriol also attenuated Ang II-induced Nox activation and ROS production, and shifted the microglia polarization from M1 to M2 phenotype. However, co-treatment with A779, a specific MasR antagonist, abrogated the antioxidant and neuroimmune modulating actions of VitD. These findings strongly indicate the involvement of ACE2/Ang(1-7)/MasR pathway in the neuroprotective mechanisms of VitD in the hypertensive brain.

3.
J Mol Neurosci ; 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31452059

RESUMO

There is evidence that corticotropin-releasing hormone receptor 1 (CRHR1) gene polymorphisms and indifferent impulsive personality traits play an important role in violent aggression in male adolescents. Genotyping for two tag single-nucleotide polymorphisms (SNP) (rs242924, rs17689966) was conducted using TaqMan SNP for 138 violent young male criminals, 98 nonviolent young male criminals, and 153 noncriminal adults. The general situation and personality traits (SSP) questionnaire was given to the young violent and nonviolent male criminal groups. The results showed that the frequency of the G allele in rs242924 of the CRHR1 gene in the violent aggression group was higher than that in the normal adult controls (P < 0.025, OR = 2.29, 95% CI = 1.13-4.62). The difference in genotype distribution was significant among the three groups (P < 0.05), and when the violent group was compared with the two control groups, no significant difference was found (P > 0.025). The impulsiveness, trait irritability, verbal trait aggression, and physical trait aggression scores in the violent group were significantly higher than those in the nonviolent group of adolescents. These findings suggest that the variance in CRHR1 gene polymorphisms and personality traits may play a role in violent aggression in male adolescents, and that the interaction of the CRHR1 gene and the impulsive personality trait may cause an increased susceptibility to violence towards others.

5.
BMC Psychiatry ; 19(1): 212, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277613

RESUMO

BACKGROUND: Narcissistic personality disorder (NPD) has never been applied in Chinese clinical practice, and the distribution of NPD in the clinical population of China is largely unknown. The current study uses two-stage clinic-based screening to investigate the frequency and clinical features of NPD in a Chinese help-seeking sample. METHODS: A total of 1402 consecutive outpatients ages 18-60 were recruited during their visit to the Shanghai Mental Health Center and screened with the Personality Diagnostic Questionnaire Fourth Edition Plus (PDQ-4+) and Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Axis II (SCID-II). The structured clinical interview was administered to estimate the rate of NPD and the frequency of each disorder criterion. RESULTS: The frequency estimate of NPD in the total sample was 4.0%. Among the 56 outpatients who met the criteria for NPD, there were more males than females, and many had a better educational background. The SCID-II interviews revealed high frequencies of diagnostic criterion 1 ("exaggerated sense of self-importance. NPD likely overlaps with Histrionic PD, Borderline PD, and Paranoid PD. This two stage screening method can enhance detection of Chinese NPD patients in clinical settings. CONCLUSIONS: Narcissism pathology is not rare in the Chinese psychiatric community when using the DSM-IV NPD criteria. Existing evidence suggests, at least indirectly, that there are important benefits of NPD diagnosis in psychiatric practice.

6.
Toxicol Appl Pharmacol ; 377: 114636, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228494

RESUMO

Chromium (Cr) is a naturally occurring metallic element found in the Earth's crust. While trivalent chromium ([Cr(III)] is considered non-carcinogenic, hexavalent chromium [Cr(VI)] has long been established as an IARC class I human carcinogen, known to induce cancers of the lung. Current literature suggests that Cr(VI) is capable of inducing carcinogenesis through both genetic and epigenetic mechanisms. Although much has been learned about the molecular etiology of Cr(VI)-induced lung carcinogenesis, more remains to be explored. In particular, the explicit epigenetic alterations induced by Cr(VI) in lung cancer including histone modifications and miRNAs, remain understudied. Through comprehensive review of available literature found between 1973 and 2019, this article provides a summary of updated understanding of the molecular mechanisms of Cr(VI)-carcinogenesis. In addition, this review identifies potential research gaps in the areas of histone modifications and miRNAs, which may prompt new niches for future research.

7.
Hepatology ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31090941

RESUMO

We read with great interest the paper entitled "Alpha-fetoprotein Decrease from >1000 to <500 ng/ml in Patients with Hepatocellular Carcinoma Leads to Improved Post-Transplant Outcomes" by Neil Mehta, et al(1). The study illustrated that alpha-fetoprotein (AFP) decrease from >1000 to <500 ng/ml before liver transplantation (LT) improved the prognosis of hepatocellular carcinoma (HCC). However, they failed to investigate the latent mechanism which decreased the clinical usage of this study. This article is protected by copyright. All rights reserved.

8.
Psychiatry ; : 1-11, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31017559

RESUMO

OBJECTIVE: Multiple and overlapping diagnoses of personality disorders (PDs) have been a major obstacle in clinical practice and research. This study aims to investigate the comorbidity of PDs in a sample of a high-risk clinical population. We propose a diagnostic model to address this critical issue. METHODS: The sample population included 982 PD patients. The PD diagnoses were concluded based on self-reported and face-to-face interviews. To address the issue of overlapping PD diagnoses, we defined the criteria for clinically distinguishing principal and subordinate PDs, and determined the frequency of each condition. RESULTS: Diagnostic overlap among PDs was quite common across all categories. Of all 982 PD patients, 436 (44.4%) met the criteria for more than one PD. In terms of specific PD diagnoses, the comorbidity rate of each PD was nearly 47.1-74.7%. The principal and subordinate PDs were distinguished accordingly. Avoidant, obsessive-compulsive, and borderline PD remain the most prevalent types of principal PD in this clinical population. CONCLUSIONS: The principal/subordinate model may be one strategy of resolving the issue of PD comorbidity in Chinese clinical settings.

9.
Biomed Chromatogr ; 33(8): e4546, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937924

RESUMO

A sensitive and reliable LC-MS/MS method was developed and validated for simultaneous quantification of the major components of Huangqi-Honghua extact in rat plasma, including hydroxysafflor yellow A (HSYA), astragaloside IV (ASIV), calycosin-7-O-ß-d-glucoside (CAG), calycosin, calycosin-3'-O-glucuronide (C-3'-G) and calycosin-3'-O-sulfate (C-3'-S). After extraction by protein precipitation with acetonitrile and methanol from plasma, the analytes were separated on a Hypersil BDS C18 column by gradient elution with acetonitrile and 5 mM ammonium acetate. The detection was carried out on a triple quadrupole tandem mass spectrometer equipped with electrospray ionization source switched between negative and positive modes. HSYA was monitored in negative ionization mode from 0 to 4.9 min, and ASIV, CAG, calycosin, C-3'-G and C-3'-S were determined in positive ionization mode from 4.9 to 10 min. The lower limits of quantification of the analytes were 6.25 ng/mL for HSYA, 0.781 ng/mL for CAG and 1.56 ng/mL for ASIV and calycosin. The intra- and inter-assay precision (RSD) values were within 13.43%, and accuracy (RE) ranged from -8.75 to 9.92%. The validated method was then applied to the pharmacokinetic study of HSYA, ASIV, CAG, calycosin, C-3'-G and C-3'-S in rat after an oral administration of Huangqi-Honghua extract.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacocinética , Flavonoides/sangue , Saponinas/sangue , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Carthamus tinctorius , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Flavonoides/química , Flavonoides/farmacocinética , Glucuronídeos/sangue , Glucuronídeos/química , Glucuronídeos/farmacocinética , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Saponinas/química , Saponinas/farmacocinética
10.
Nanotechnology ; 30(26): 26LT01, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30836332

RESUMO

Freestanding graphene films are desired to be widely applied in biosensor fabrication due to their distinctive physical properties and improved performance. Chemical vapor deposition has been developed to efficiently fabricate large-area graphene. However, some of the fabricated graphene films might break or be contaminated in the current transferring step using polymers. A stable and high-quality transfer method is needed. Herein, we report on an advanced transfer method of large-area graphene film which uses fullerene as a supporting substrate. Unlike polymers, which are commonly eliminated by being dissolved in an organic solution, fullerene can be easily removed by evaporation in a vacuum because it has a different heat stability to graphene. By using the improved transferring method, the percentage of integrated freestanding films after transferring was increased from 60.7% to 93.4%. The vacuum is beneficial in terms of keeping the brittle freestanding films intact. Graphene films transferred using fullerene showed an advanced flatness and a simplicial elementary composition in comparison to those transferred using polymers. Even through there is trace residue, this stable allotrope of graphene is considered to have almost no impact on biomolecule sensing. These advantages make the fullerene transferring method an attractive candidate for fabricating large-area freestanding graphene films, especially for using in the field of biochemistry analysis and biosensors.

11.
Carcinogenesis ; 40(3): 393-402, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30916759

RESUMO

The special AT-rich DNA binding protein (SATB2) is a nuclear matrix-associated protein and an important transcription factor for biological development, gene regulation and chromatin remodeling. Aberrant regulation of SATB2 has been found to highly correlate with various types of cancers including lung, colon, prostate, breast, gastric and liver. Recent studies have revealed that a subset of small non-coding RNAs, termed microRNAs (miRNAs), are important regulators of SATB2 function. As post-transcriptional regulators, miRNAs have been found to have fundament importance maintaining normal cellular development. Evidence suggests that multiple miRNAs, including miR-31, miR-34, miR-182, miR-211, miR-599, are capable of regulating SATB2 in cancers of the lung, liver, colon and breast. This review examines the molecular functions of SATB2 and miRNAs in the text of cancer development and potential strategies for cancer therapy with a focus on systemic miRNA delivery.

12.
Gene ; 699: 145-154, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30876822

RESUMO

BACKGROUND: Detecting heteroplasmic variations in the mitochondrial genome can help identify potential pathogenic possibilities, which is significant for disease prevention. The development of next-generation sequencing changed the quantification of mitochondrial DNA (mtDNA) heteroplasmy from scanning limited recorded points to the entire mitochondrial genome. However, due to the presence of nuclear mtDNA homologous sequences (nuMTs), maximally retaining real variations while excluding falsest heteroplasmic variations from nuMTs and sequencing errors presents a dilemma. RESULTS: Herein, we used an improved method for detecting low-frequency mtDNA heteroplasmic variations from whole genome sequencing data, including point variations and short-fragment length alterations, and evaluated the effect of this method. A two-step alignment was designed and performed to accelerate data processing, to obtain and retain the true mtDNA reads and to eliminate most nuMTs reads. After analyzing whole genome sequencing data of K562 and GM12878 cells, ~90% of heteroplasmic point variations were identified in MitoMap. The results were consistent with the results of an amplification refractory mutation system qPCR. Many linkages of the detected heteroplasmy variations were also discovered. CONCLUSIONS: Our improved method is a simple, efficient and accurate way to mine mitochondrial low-frequency heteroplasmic variations from whole genome sequencing data. By evaluating the highest misalignment possibility caused by the remaining nuMTs-like reads and sequencing errors, our procedure can detect mtDNA heteroplasmic variations whose heteroplasmy frequencies are as low as 0.2%.


Assuntos
Genoma Mitocondrial/genética , Mitocôndrias/genética , Mutação/genética , Linhagem Celular Tumoral , DNA Mitocondrial/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Células K562 , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos
13.
Mol Med Rep ; 19(4): 3009-3020, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816517

RESUMO

Stroke is the second most frequent cause of mortality, resulting in a huge societal burden worldwide. Timely reperfusion is the most effective therapy; however, it is difficult to prevent ischemia/reperfusion (I/R) injury. In traditional Chinese medicine, hydroxysafflor yellow A (HSYA) has been widely used for the treatment of cerebrovascular disease and as a protective therapy against I/R injury. Evidence has demonstrated that HSYA could reduce the levels of reactive oxygen species and suppress cellular apoptosis; however, whether HSYA alters the metabolic profile as its underlying mechanism for neuroprotection remains unknown. In the present study, using a metabolomic screening, phenylalanine was identified to significantly increase in an experimental model of mouse cerebral I/R injury. Notably, western blotting and qPCR analysis were conducted to test the expression level of apoptosis­associated factors, and HSYA was identified to be able to protect neuronal cells by reducing phenylalanine level associated with I/R injury. Additionally, these findings were confirmed in primary mouse neurons and PC12 cells exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) stress. Of note, HSYA was observed to regulate the mRNA expression of key metabolic enzymes, phenylalanine hydroxylase, tyrosine aminotransferase and aspartate aminotransferase, which are responsible for phenylalanine metabolism. Furthermore, by performing mitochondrial labeling and JC­1 fluorescence assay, HSYA was identified to promote mitochondrial function and biogenesis suppressed by OGD/R. The findings of the present study demonstrated that I/R injury could increase the levels of phenylalanine, and HSYA may inhibit phenylalanine synthesis to enhance mitochondrial function and biogenesis for neuroprotection. The present study proposed a novel metabolite biomarker for cerebral I/R injury and the evaluated the efficacy of HSYA as a potential therapeutic treatment I/R injury.


Assuntos
Isquemia Encefálica/metabolismo , Chalcona/análogos & derivados , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fármacos Neuroprotetores/farmacologia , Fenilalanina/biossíntese , Quinonas/farmacologia , Traumatismo por Reperfusão/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Isquemia Encefálica/patologia , Chalcona/farmacologia , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Biogênese de Organelas , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Resultado do Tratamento
14.
Fish Shellfish Immunol ; 87: 534-545, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30721776

RESUMO

Enterocytozoon hepatopenaei (EHP) causes hepatopancreatic microsporidiosis (HPM) in shrimp. HPM is not normally associated with shrimp mortality, but is associated with significant growth retardation. In this study, the responses induced by EHP were investigated in hepatopancreas of shrimp Litopenaeus vannamei using proteomics and metabolomics. Among differential proteins identified, several (e.g., peritrophin-44-like protein, alpha2 macroglobulin isoform 2, prophenoloxidase-activating enzymes, ferritin, Rab11A and cathepsin C) were related to pathogen infection and host immunity. Other proteomic biomarkers (i.e., farnesoic acid o-methyltransferase, juvenile hormone esterase-like carboxylesterase 1 and ecdysteroid-regulated protein) resulted in a growth hormone disorder that prevented the shrimp from molting. Both proteomic KEGG pathway (e.g., "Glycolysis/gluconeogenesis" and "Glyoxylate and dicarboxylate metabolism") and metabolomic KEGG pathway (e.g., "Galactose metabolism" and "Biosynthesis of unsaturated fatty acids") data indicated that energy metabolism pathway was down-regulated in the hepatopancreas when infected by EHP. More importantly, the changes of hormone regulation and energy metabolism could provide much-needed insight into the underlying mechanisms of stunted growth in shrimp after EHP infection. Altogether, this study demonstrated that proteomics and metabolomics could provide an insightful view into the effects of microsporidial infection in the shrimp L. vannamei.


Assuntos
Enterocytozoon/fisiologia , Metaboloma/imunologia , Penaeidae/genética , Penaeidae/imunologia , Proteoma/imunologia , Animais , Hepatopâncreas/imunologia , Penaeidae/metabolismo
15.
Environ Pollut ; 247: 586-594, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30708321

RESUMO

Around the globe, worsening air pollution is spawning major public health and environmental concerns, especially in the poorest and most populous cities. As a major secondary air pollutant, ozone is a potential risk factor for exacerbated asthma, although the underlying mechanisms remain uncertain. In this study, we aim to investigate the role of ozone on asthma exacerbation using a classic asthmatic model with allergic airway inflammation by treating Balb/c mice with ovalbumin (OVA). Our study shows ozone exposure significantly exacerbated OVA-induced asthmatic phenotypes, including serum immunoglobulin, Th cytokines, inflammatory cell counts, mucus production, airway remodeling, and airway hyper-responsiveness (AHR). Interestingly, expression of transient receptor potential cation channel subfamily V member1 (TRPV1) was also significantly elevated in ozone-exacerbated asthmatic mice and that treatment with TRPV1 antagonist effectively suppressed AHR, airway inflammation and remodeling. The underlying mechanisms of these effects may be associated with suppression of neuropeptide calcitonin gene-related peptide (CGRP) and thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. Base on the role of TRPV1 in allergic asthma, this study further revealed that inhibition of TRPV1 by TRPV1 antagonist has significant anti-inflammatory effects on ozone-induced asthma exacerbation in this study. Induction of TRPV1 expression may be an important mechanism underlying the increased risks for asthma after exposure to environmental pollutants.


Assuntos
Poluentes Atmosféricos/toxicidade , Asma/induzido quimicamente , Ozônio/toxicidade , Canais de Cátion TRPV/metabolismo , Animais , Asma/metabolismo , Citocinas , Modelos Animais de Doenças , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Ozônio/metabolismo , Sistema Respiratório/metabolismo , Canais de Receptores Transientes de Potencial/metabolismo
16.
J Cell Biochem ; 120(6): 10495-10504, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30635938

RESUMO

Tongue cancer remains a massive threat to public health due to the high rate of metastasis. Tumor cell epithelial-mesenchymal transition (EMT), which can be induced by transforming growth factor ß1 (TGFß1), has been regarded as a significant contributor to cancer invasion and migration. In our previous study, long noncoding RNA (lncRNA) MALAT1/miR-124/JAG1 axis modulates the growth of tongue cancer. In addition to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), another lncRNA, urothelial cancer associated 1 (UCA1), can promote EMT and cancer metastasis. In the present study, UCA1 was overexpressed in tongue cancer tissues and cell lines. UCA1 overexpression was correlated to the poorer prognosis of patients with tongue cancer. UCA1 knockdown significantly suppressed TGFß1-induced tongue cancer cell invasion and EMT by decreasing vimentin and increasing E-cadherin. Regarding the molecular mechanism, UCA1 could directly bind to microRNA-124 (miR-124) and negatively regulate each other. UCA1 knockdown ameliorated, whereas miR-124 inhibition exacerbated TGFß1-induced EMT and invasion in tongue cancer cells through miR-124 downstream jagged 1 (JAG1) and Notch signaling. Moreover, miR-124 inhibition partially impaired the effect of UCA1 knockdown. In tongue cancer tissues, miR-124 expression was remarkably decreased, whereas JAG1 mRNA expression was increased. miR-124 was negatively correlated with UCA1 and JAG1. UCA1 and JAG1 were positively correlated. In summary, we provided a novel mechanism by which the EMT process and cancer cell invasion in tongue cancer could be modulated from the perspective of lncRNA-miRNA-mRNA regulation.

17.
Annu Rev Pharmacol Toxicol ; 59: 537-554, 2019 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-30625284

RESUMO

Metal exposure is pervasive and not limited to sporadic poisoning events or toxic waste sites. Hundreds of millions of people around the globe are affected by chronic metal exposure, which is associated with serious health concerns, including cancer, as demonstrated in a variety of studies at the molecular, systemic, and epidemiologic levels. Metal-induced toxicity and carcinogenicity are sophisticated and complex in nature. This review provides a broad context and holistic view of currently available studies on the mechanisms of metal-induced carcinogenesis. Specifically, we focus on the five most prevalent carcinogenic metals, arsenic, nickel, cadmium, chromium, and beryllium, and their potential to drive carcinogenesis in humans. A comprehensive understanding of the mechanisms behind the development of metal-induced cancer can provide valuable insights for therapeutic intervention involving molecular targets in metal-induced carcinogenesis.

18.
Chemosphere ; 214: 430-435, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30273876

RESUMO

Fluoride is becoming an ineluctable environmental pollutant and its longterm exposure would cause fluorosis and irreversible brain damage, but the molecular mechanisms remain far from fully understood. In the present study, we firstly evaluated the glycogen synthase kinase 3ß (GSK-3ß)/ß-catenin pathway in the hippocampus of rats exposed to fluoride, given the well-established role of GSK-3ß/ß-catenin pathway in neuronal death and survival. Our data showed that sustained exposure to 50 mg/L and 100 mg/L NaF in drinking water dose-dependently induced neuronal loss and apoptosis in rat hippocampus. Neurogenesis was also weakened by fluoride administration in the hippocampal dentate gyrus region. Additionally, the synaptic markers, synaptophysin (SYP) and post-synaptic density 95 (PSD95) protein levels, were decreased by 100 mg/L NaF treatment, whereas 50 mg/L NaF only reduced SYP expression, indicating a compromised synaptic function. We further demonstrated that NaF, especially the higher dose, induced GSK-3ß activity, with decreased inactive phosphorylated GSK-3ß levels and increased GSK-3ß, the active form of the kinase. Correspondingly, downstream ß-catenin signaling was undermined by NaF treatment as evidenced by the fact that both two doses of NaF decreased nucleus ß-catenin status and the higher dose of NaF also reduced cytoplasmic ß-catenin protein expression. Taken together, the present study firstly showed the aberrant changes of GSK-3ß/ß-catenin signaling in the fluoride-exposed brain, highlighting the involvement of GSK-3ß/ß-catenin signaling in the fluoride-induced neurotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Fluoretos/toxicidade , Glicogênio Sintase Quinase 3 beta/metabolismo , Neurogênese/efeitos dos fármacos , Plasticidade Neuronal , Neurônios/patologia , beta Catenina/metabolismo , Animais , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 40(5): 710-713, 2018 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-30404707

RESUMO

Lung cancer is mostly characterized by a pulmonary solid mass on CT. In rare cases,patients do not have these typical manifestation but present with diffusely-distributed small nodules and pulmonary bullae,which can easily be misdiagnosed. A special case of lung adenocarcinoma was managed in our hospital from September 24th to December 19th in 2016. Under high-resolution CT,multiple nodules were seen in both lungs,mostly in the upper lungs,involving the pleura and interlobular fissures. Some nodules had cystic changes. A large bulla was seen in the left upper lung. Its wall was thickened with multiple nodules. Lung adenocarcinoma was pathologically confirmed.

20.
Free Radic Biol Med ; 129: 440-445, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30336249

RESUMO

Doxorubicin (Dox) is an effective anti-cancer agent, whose clinical use is limited by the cytotoxicity in non-target tissues, especially the heart and brain. The drug-induced neuronal damage is primarily mediated by oxidative stress, in which autophagy plays a central role. Although numerous studies indicate the involvement of autophagy in neurodegenerative diseases and brain injury, the evidence concerning autophagic process in Dox-induced neuronal death is limited. We found that repeated Dox administration induced the protein expression of LC3II and P62 and impaired autophagic flux with enhanced autophagasome accumulation in rat hippocampus, whereas two weeks after the cessation of Dox treatment, the autophagic process was restored, even stimulated, with normalized protein levels of LC3II and P62 and enhanced expression of Becline-1, indicating a compensatory response in the recovery state. Likewise, while repeated Dox exposure inhibited the hippocampal expression of lysosomal-associated membrane protein 2 (LAMP2) and cathepsin D (CTSD), and suppressed CTSD activity, the Dox-induced impaired autophagy-lysosome pathway was also restored in rats following two weeks of recovery. To further verify the role of autophagy, the autophagy inhibitor, 3-methyladenine (3-MA), was administrated daily for the two weeks of recovery period. Our data demonstrated that while the animals in the recovery state showed a significant trend to decreased oxidative damage, normalized antioxidative system and ameliorated endoplasmic reticulum (ER) stress compared with Dox-induced toxic model, 3-MA treatment abrogated the recovering process, resulting in sustained oxidative and ER stress and neuronal apoptosis. Collectively, the present study firstly provided the evidence for the involvement of autophagy in both development and recovery of Dox-induced neurotoxicity, highlighting a novel target for mitigating the chemotherapy-induced neuronal damage.

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