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1.
Drug Des Devel Ther ; 15: 245-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519190

RESUMO

Background: Paeoniflorin (Pae) possesses anti-tumor activity in various malignancies. However, it is unclear whether Pae plays a sensitizer role in breast cancer (BC) and the molecular mechanisms involved in this process. Our oligonucleotide microarray revealed that microRNA (miR)-15b is the most significantly downregulated miRNA in MCF-7/4-hydroxytamoxifen (4-OHT) cells treated with Pae. This paper summarized the relevance of Pae in BC cell endocrine resistance to tamoxifen (Tam) and the molecular mechanisms involved miR-15b expression. Materials and Methods: 4-OHT-resistant BC cell lines were developed and treated with different concentrations of Pae. Flow cytometry, lactose dehydrogenase activity, caspase-3 activity, colony formation, and EdU assays were carried out to assess the impact of Pae on BC cells. Differentially expressed miRNAs in BC cells treated with Pae were analyzed by microarray. Targeting mRNAs of screened miR-15b as well as the binding of forkhead box O1 (FOXO1) to the cyclin D1 (CCND1) promoter sequence were predicted through bioinformatics analysis. Finally, the expression of ß-catenin signaling-related genes in cells was detected by Western blotting. Results: Pae (100 µg/mL) inhibited the clonality and viability of BC cells, while enhancing apoptosis in vitro. Pae also repressed miR-15b expression. Overexpression of miR-15b restored the growth and resistance of BC cells to 4-OHT. Moreover, Pae promoted FOXO1 expression by downregulating miR-15b, thereby transcriptionally inhibiting CCND1 and subsequently blocking ß-catenin signaling. Conclusion: Pae inhibits 4-OHT resistance in BC cells by regulating the miR-15b/FOXO1/CCND1/ß-catenin pathway.

2.
Eur J Pharmacol ; : 173962, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33610599

RESUMO

Reperfusion causes undesirable damage to the ischemic myocardium while restoring the blood flow. In this study, we evaluated the effects of dexpramipexole (DPX) on myocardial injury induced by ischemia/reperfusion (I/R) in-vivo and the hypoxia/reoxygenation (HR) in-vitro and examined the functional mechanisms of DPX. DPX protected cells against H/R-induced mitochondrial dysfunction and prevented H/R damage. Both myocardial infarct size and tissue damage due to I/R was reduced upon DPX treatment. We discovered that DPX enhanced mitophagy in-vivo and in-vitro, which was accompanied by enhanced expression of PINK1 and Parkin. Knock-down of PINK1 and Parkin by specific siRNAs reversed DPX-induced inhibition of myocardial I/R injury. These findings suggest that DPX might protect against myocardial injury via PINK1 and Parkin.

3.
Mol Cancer ; 20(1): 28, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33546704

RESUMO

The overlapping metabolic reprogramming of cancer and immune cells is a putative determinant of the antitumor immune response in cancer. Increased evidence suggests that cancer metabolism not only plays a crucial role in cancer signaling for sustaining tumorigenesis and survival, but also has wider implications in the regulation of antitumor immune response through both the release of metabolites and affecting the expression of immune molecules, such as lactate, PGE2, arginine, etc. Actually, this energetic interplay between tumor and immune cells leads to metabolic competition in the tumor ecosystem, limiting nutrient availability and leading to microenvironmental acidosis, which hinders immune cell function. More interestingly, metabolic reprogramming is also indispensable in the process of maintaining self and body homeostasis by various types of immune cells. At present, more and more studies pointed out that immune cell would undergo metabolic reprogramming during the process of proliferation, differentiation, and execution of effector functions, which is essential to the immune response. Herein, we discuss how metabolic reprogramming of cancer cells and immune cells regulate antitumor immune response and the possible approaches to targeting metabolic pathways in the context of anticancer immunotherapy. We also describe hypothetical combination treatments between immunotherapy and metabolic intervening that could be used to better unleash the potential of anticancer therapies.

4.
Health Commun ; : 1-8, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33601987

RESUMO

Patient satisfaction is an important intermediate outcome of patient-provider encounters, linking face-to-face interactions between patients and medical professionals with patients' well-being after consultations. Today, physician review websites provide a new venue for the study of patient satisfaction, as patients are utilizing such websites to evaluate their encounters with physicians. This study examined how parents of pediatric patients in China evaluated their pediatricians and factors associated with patient satisfaction through a qualitative content analysis of reviews (n = 7230) on the "Good Doctor Website" (haodf.com), China's largest physician review platform. Reviews were chosen from all reviews of pediatricians in eight top-tier hospitals in four major cities. Three dimensions of patient satisfaction were identified: pediatricians' interpersonal manners (including friendliness, listening to patients, heartfelt encouragement, and clear explanation), ethics (including rejecting red envelopes and kickbacks and cost awareness), and medical competence/overall health outcome. This study contributes to a culturally sensitive understanding of patient satisfaction and further explains the tense physician-patient relationship in China. Practically, our findings can inform the training of pediatricians in China.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33604715

RESUMO

PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.

6.
Pharmacol Res ; : 105464, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33515707

RESUMO

BACKGROUND: An individual's level of lower limb motor function is associated with his or her disability level after stroke, and motor improvement may lead to a better prognosis and quality of life. Data from animal models show that Qizhitongluo (QZTL) capsule facilitates recovery after focal brain injury. We aimed to validate the efficacy and safety of the QZTL capsule for promoting lower limb motor recovery in poststroke patients. METHODS: In this randomized, multicenter, double-blind, placebo- and active-controlled trial from 13 sites in China, participants with ischemic stroke and Fugl-Meyer motor scale (FMMS) scores of <95 were eligible for inclusion. Patients were randomly assigned in a 2:1:1 ratio to the QZTL group, Naoxintong (NXT) group or placebo group for 12 weeks at 15-28 days after the onset of stroke. The primary outcome was the change in the Lower Limb FMMS (FMMS-LL) score from baseline over the 12-week intervention period. RESULTS: 622 participants were randomly assigned to the QZTL group (309), NXT group (159), or placebo group (154). The FMMS-LL score increased by 4.81 points (95 % CI, 4.27-5.35) in the QZTL group, by 3.77 points (95 % CI, 3.03-4.51) in the NXT group and by 3.00 points (95 % CI, 3.03-4.51) in the placebo group at week 12. The QZTL group showed significantly larger improvements compared with the placebo group at each interview from weeks 4-12 (difference, 0.89 [0.30,1.49] at week 4, P = 0.0032; difference, 1.83[1.01,2.66] at 90 days poststroke, P < 0.0001; difference, 1.81[0.88,2.74] at week 12, P = 0.0001). CONCLUSION: The QZTL capsule is an effective treatment for lower limb motor impairment. The finding indicates that the QZTL capsule may be used as a potential new strategy for stroke rehabilitation.

7.
Int J Mol Med ; 47(2): 708-718, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33416098

RESUMO

A large human natural single­chain fragment variable (scFv) phage library was constructed based on Cre­LoxP recombination, and used to successfully identify antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). The library was derived from 400 blood samples, 30 bone marrow samples, and 10 cord blood samples from healthy donors. Lymphocytes were isolated from each sample and cDNA was synthesized using reverse transcription­quantitative PCR. Two­step overlap PCR was then used for scFv synthesis using a LoxP peptide as the linker. The scFv gene was inserted into the phagemid vector pDF by enzymatic digestion and ligation, and then transformed into Escherichia coli (E. coli) SS320 to establish a primary antibody library in the form of scFvs. A primary antibody library consisting of 5x107 peripheral blood and umbilical cord blood sources, as well as a primary antibody library of 5x107 bone marrow samples were obtained. By optimizing the recombination conditions, the primary phage library was used to infect E. coli BS1365 strain (which expresses the Cre enzyme), and a human scFv recombinant library with a size of 1x1011 was obtained through Cre­LoxP enzyme­mediated heavy and light chain replacement and recombination. This constructed recombinant library was employed to screen for antibodies against recombinant PCSK9. After four rounds of selection, a fully human antibody (3D2) was identified with a binding affinity of 1.96±1.56ⅹ10­10 M towards PCSK9. In vitro, the PCSK9/low­density lipoprotein receptor (LDLR) pathway of Hep­G2 cells was inhibited by 3D2 treatment, thereby increasing LDL uptake in these cells. In addition, combination treatment with 3D2 and statin was more effective at increasing LDLR levels than treatment with 3D2 or statin alone. Furthermore, 3D2 resulted in a 3­fold increase in hepatic LDLR levels, and lowered total serum cholesterol by up to 61.5% in vivo. Taken together, these results suggest that the constructed human Cre­LoxP scFv phage display library can be used to screen fully human scFv, and that 3D2 may serve as a candidate hypolipidemic therapy.

8.
J Med Internet Res ; 23(1): e23262, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399543

RESUMO

BACKGROUND: Social media platforms such as YouTube are hotbeds for the spread of misinformation about vaccines. OBJECTIVE: The aim of this study was to explore how individuals are exposed to antivaccine misinformation on YouTube based on whether they start their viewing from a keyword-based search or from antivaccine seed videos. METHODS: Four networks of videos based on YouTube recommendations were collected in November 2019. Two search networks were created from provaccine and antivaccine keywords to resemble goal-oriented browsing. Two seed networks were constructed from conspiracy and antivaccine expert seed videos to resemble direct navigation. Video contents and network structures were analyzed using the network exposure model. RESULTS: Viewers are more likely to encounter antivaccine videos through direct navigation starting from an antivaccine video than through goal-oriented browsing. In the two seed networks, provaccine videos, antivaccine videos, and videos containing health misinformation were all found to be more likely to lead to more antivaccine videos. CONCLUSIONS: YouTube has boosted the search rankings of provaccine videos to combat the influence of antivaccine information. However, when viewers are directed to antivaccine videos on YouTube from another site, the recommendation algorithm is still likely to expose them to additional antivaccine information.

9.
Health Commun ; 36(1): 74-80, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33167736

RESUMO

Emerging infectious disease (EID) outbreaks such as the ongoing COVID-19 pandemic create unknown risks, uncertainty, and anxiety around the world. Accurate and timely information can help the public understand the outbreak and manage their lives. Presented here is a study of how residents of Hubei Province, the epicenter of the COVID-19 outbreak in China, use media for information seeking, scanning, and sharing while under lockdown through in-depth interviews. We find that (1) individuals primarily acquire information through information scanning from official governmental sources, (2) information sharing is more frequent with family members through private channels than with one's extended social networks and the general public through pubic channels mostly due to concerns with censorship, and (3) individuals' information need and information use change substantially during different stages of the outbreak. These findings provide insights into how individuals in China use different media for information during an unprecedented public health crisis and make sense of the limited and often confusing and contradictory information that is available to them. Such findings can inform future health communication efforts during EID outbreaks.


Assuntos
/epidemiologia , Informação de Saúde ao Consumidor/métodos , Comunicação em Saúde/métodos , Adulto , China/epidemiologia , Feminino , Humanos , Comportamento de Busca de Informação , Relações Interpessoais , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Pandemias , Pesquisa Qualitativa , Mídias Sociais
10.
J Cell Physiol ; 236(2): 1418-1431, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32677057

RESUMO

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers, and long noncoding RNAs (lncRNAs) regulate gene expression or activities. This study investigated the role of lncRNA LINC00551 in ESCC development and progression. Three paired ESCC and normal tissues were subjected to next-generation sequencing and we identified 82 upregulated and 60 downregulated lncRNAs, including LINC00551, which was confirmed to markedly downregulated in 78 ESCC tissues and in the Gene Expression Profiling Interactive Analysis data set. Downregulated LINC00551 expression was associated with lymph node metastasis, advanced TNM stage, and tumor size. Moreover, downregulated LINC00551 expression was also associated with poor progression-free survival and overall survival of ESCC patients. In vitro and in vivo, LINC00551 overexpression inhibited ESCC cell proliferation and invasion, whereas knockdown of LINC00551 expression promoted ESCC cell proliferation and invasion. RNA pull-down and mass spectrometry assays identified the potential LINC00551 binding proteins, and HSP27 was a promising LINC00551 targeting proteins after RNA immunoprecipitation assay. At the protein level, LINC00551 bound to and decreased HSP27 phosphorylation, and in turn, downregulated ESCC cell proliferation and invasion. The current study demonstrated the functional significance of LINC00551 in ESCC development, progression, and prognosis. Further study will assess LINC00551 as a novel prognostic marker or therapeutic target for ESCC.

11.
Immun Inflamm Dis ; 9(1): 288-298, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332750

RESUMO

OBJECTIVE: Emerging articles have profiled the relations between microRNAs and viral myocarditis. This research was unearthed to explore the capacity of miR-425-3p on cardiomyocyte apoptosis in mice with viral myocarditis and its mechanism. METHODS: A total of 120 mice were classified into 4 groups in a random fashion (n = 30). The mice were intraperitoneally injected with coxsackievirus type B3 (CVB3) to induce myocarditis. On the 7th day after CVB3 infection, 10 mice in each group were euthanized to assess the heart function indices of mice, observe the pathological conditions, detect myocardial tissue apoptosis, and measure the inflammatory factor levels in myocardial tissues. Expression of miR-425-3p, transforming growth factor (TGF-ß1), and apoptosis-associated proteins in myocardial tissues was determined. The remaining 20 mice in each group were used for survival observation. The luciferase activity assay was implemented to validate the relationship between miR-425-3p and TGF-ß1. miR-425-3p mimic was transfected into mouse cardiomyocytes HL-1 and then infected with CVB3 to further verify the regulatory effect of miR-425-3p on the cardiomyocyte apoptosis in viral myocarditis. RESULTS: miR-425-3p was lowly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR-425-3p improved the cardiac function, alleviated pathological conditions, reduced cardiomyocyte apoptosis, decreased Bax and cleaved Caspase-3 expression, elevated Bcl-2 expression, decreased levels of inflammatory factors and improved survival rate of mice with viral myocarditis. Luciferase activity assay verified that miR-425-3p could bind to TGF-ß1, and overexpressed miR-425-3p suppressed TGF-ß1, p-smad2/smad2 and p-smad3/smad3 expression. In vitro experiments further verified that overexpression of miR-425-3p inhibited the apoptosis of CVB3-HL-1 cells, and the addition of TGF-ß1 would reverse this effect. CONCLUSION: Our research indicates that miR-425-3p is poorly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR-425-3p inhibits cardiomyocyte apoptosis and myocardial inflammation in mice with viral myocarditis as well as improves their survival rates through suppressing the TGF-ß1/smad axis.

12.
Public Underst Sci ; 30(2): 153-168, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33353491

RESUMO

The COVID-19 pandemic is called the first infodemic in history. Those first confronted by the enormous challenge of fighting this infodemic to save their lives were the people of Hubei Province in China. To understand how they defined and processed rumors, we conducted an interview study with Hubei residents when they were under lockdown. We found that they typically defined rumors in terms of one or two of three features: non-factual information, information unsanctioned by the government, and information causing panic. They reported low motivation in verifying the information and often either rejected any information they perceived as suspicious or waited for the government to debunk rumors. Even among those who tried to verify information, most relied exclusively on heuristic processing cues such as source credibility, linguistic and visual cues, and intuition. Systematic processing strategies such as fact-checking and discussing with family and friends were seldom used.


Assuntos
/epidemiologia , Controle de Doenças Transmissíveis/métodos , Confiabilidade dos Dados , Surtos de Doenças/prevenção & controle , Pandemias , Opinião Pública , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
J Hazard Mater ; 408: 124854, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33370696

RESUMO

The male pregnancy of seahorses is unique, but their reproductive response to environmental disturbances has not yet been clarified. Tributyltin (TBT) is known to have an endocrine disrupting effect on the reproductive system of coastal marine organisms. This study evaluated the potential effects of exposure to environmentally relevant concentrations of TBT on the development of gonads and brood pouch of the lined seahorse (Hippocampus erectus). Physiological, histological, and transcriptional analyses were conducted, and results showed that high levels of TBT bioaccumulation occurred in male and female seahorses. TBT led to ovarian follicular atresia and apoptosis with the elevation of androgen levels, accompanied by the induction of genes associated with lysosomes and autophagosomes. Comparative transcriptional analyses revealed the likely inhibition of spermatogenesis via the suppression of cyclic AMP and androgen synthesis. Notably, the transcriptional profiles showed that TBT potentially affects the immune system, angiogenesis, and embryo nourishment of the brood pouch, which indicates that it has negative effects on the male reproductive system of seahorses. In summary, this study reveals that environmental levels of TBT potentially affect the reproductive efficiency of seahorses, and may ultimately lead to a reduction in their populations in coastal environments.

14.
Biosci Rep ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300046

RESUMO

Wilson's disease (WD) is an autosomal recessive disease caused by mutation of the ATPase copper transporting beta (ATP7B) gene, resulting in abnormal copper metabolism. We aimed to investigate the protective effect of GanDouLing (GDL) on neural stem cell (NSC) function in a mouse model of WD. NSCs were treated with different concentrations of GDL alone or in combination with penicillamine, following which we evaluated cellular growth, apoptosis, and differentiation. Nuclear factor E2-related factor 2 (Nrf2) pathway and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation were analyzed via Western blotting. Treatment with GDL alone or in combination with penicillamine significantly increased proliferation and inhibited apoptosis of NSCs in a dose-dependent manner. In addition, GDL treatment remarkably promoted differentiation of NSCs. Consistently, levels of class III ß-tubulin (Tuj1) and microtubule-associated protein 2 (MAP2) were significantly elevated, whereas glial fibrillary acidic protein (GFAP) levels were obviously suppressed in the presence of GDL or penicillamine. In vivo assays confirmed that GDL increased the ratio of Ki67+, Tuj1+, and MAP2+ cells and suppressed apoptosis in the hippocampal region in WD mice. Behavioral assays revealed that both GDL and penicillamine improved memory ability in WD models. Mechanistically, GDL treatment led to activation of Nrf2 signaling and suppression of the NLRP3 inflammasome in WD mice. Notably, inhibition of Nrf2 signaling reversed the protective effects of GDL on hippocampal NSCs. Collectively, these findings demonstrate that GDL exerts a protective effect on NSCs and promotes neurogenesis by targeting Nrf2 signaling and the NLRP3 inflammasome in WD.

15.
J Mater Chem B ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33306079

RESUMO

rHDL is a synthesized drug delivery nanoplatform exhibiting excellent biocompatibility, which possesses most of the advantages of HDL. rHDL shows almost no toxicity and can be degraded to non-toxic substances in vivo. The severe limitation of the application of various antitumor agents is mainly due to their low bioavailability, high toxicity, poor stability, etc. Favorably, antitumor drug-loaded rHDL nanoparticles (NPs), which are known as an important drug delivery system (DDS), help to change the situation a lot. This DDS shows an outstanding active-targeting ability towards tumor cells and improves the therapeutic effect during antitumor treatment while overcoming the shortcomings mentioned above. In the following text, we will mainly focus on the various applications of rHDL in tumor targeted therapy by describing the properties, preparation, receptor active-targeting ability and antitumor effects of antineoplastic drug-loaded rHDL NPs.

16.
J Health Commun ; : 1-11, 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33372857

RESUMO

Social media health influencers play an increasingly important role in disseminating health-related information to the public. To explore how health influencers in China communicate with their followers, we conducted a content analysis of the top ten health influencers' posts (n = 1000) on Sina Weibo guided by the Extended Parallel Processing Model (EPPM) and the transportation theory. These posts were coded in terms of demographic information, topics, message properties (informative, persuasive, and interactive), EPPM variables, and types of evidence (statistical and narrative) used. Results showed that these influencers had a clear emphasis on women's health (OB/GYN diseases and risks related to pregnancy and childcare) and beauty and skincare (in terms of risks and benefits). Overall, they used low fear appeal and high efficacy messages. However, messages containing efficacy information were less likely to be liked. These influencers relied heavily on narrative evidence; however, there was no significant relationship between the use of either narrative or statistical evidence and the number of likes. Differences in the communication strategies in posts about different diseases did exist but were not prevalent.

17.
Front Immunol ; 11: 570993, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33329533

RESUMO

Corona virus disease 2019 (COVID-19) has caused a global outbreak and severely posed threat to people's health and social stability. Mounting evidence suggests that immunopathological changes, including diminished lymphocytes and elevated cytokines, are important drivers of disease progression and death in coronavirus infections. Cytokine storm not only limits further spread of virus in the body but also induces secondary tissue damage through the secretion of large amounts of active mediators and inflammatory factors. It has been determined that cytokine storm is a major cause of deaths in COVID-19; therefore, in order to reverse the deterioration of severe and critically ill patients from this disease, the cytokine storm has become a key therapeutic target. Although specific mechanisms of the occurrences of cytokine storms in COVID-19 have not been fully illuminated, hyper-activated innate immune responses, and dysregulation of ACE2 (angiotensin converting enzyme 2) expression and its downstream pathways might provide possibilities. Tailored immunoregulatory therapies have been applied to counteract cytokine storms, such as inhibition of cytokines, corticosteroids, blood purification therapy, and mesenchymal stem cell therapy. This review will summarize advances in the research of cytokine storms induced by COVID-19, as well as potential intervention strategies to control cytokine storms.


Assuntos
Síndrome da Liberação de Citocina , Surtos de Doenças , Imunoterapia , /imunologia , /imunologia , /epidemiologia , /terapia , Síndrome da Liberação de Citocina/epidemiologia , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/terapia , Humanos , Imunidade Inata/imunologia
18.
J Trace Elem Med Biol ; 64: 126677, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33246299

RESUMO

OBJECTIVES: Selenium (Se) was a potential anticancer micronutrient with proposed epigenetic effect. However, the Se-induced epigenome in breast cancer cells was yet to be studied. METHODS: The profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) in breast cancer cells treated with sodium selenite were examined by microarrays. We verified the epigenetic modifications by integrating their predicted target genes and differentially expressed mRNAs. The epigenetically regulated genes were further validated in a breast cancer cohort by associating with tumor progression. We conducted a series of bioinformatics analyses to assess the biological function of these validated genes and identified the critical genes. RESULTS: The Se-induced epigenome regulated the expression of 959 genes, and 349 of them were further validated in the breast cancer cohort. Biological function analyses suggested that these validated genes were enriched in several cancer-related pathways, such as PI3K/Akt and metabolic pathways. Based on the degrees of expression change, hazard ratio difference, and connectivity, NEDD4L and FMO5 were identified as the critical genes. CONCLUSIONS: These results confirmed the epigenetic effects of sodium selenite and revealed the epigenetic profiles in breast cancer cells, which would help understand the mechanisms of Se against breast cancer.

19.
Front Cell Dev Biol ; 8: 594112, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240891

RESUMO

Background: N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment played crucial roles in cancer development. However, their association in gliomas remains to be fully elucidated. Methods: A total of 2144 glioma patients from CGGA, TCGA, and Rembrandt databases were extracted in our study, in which 325 were set as the training cohort and 1819 were defined as the validation cohort. Survival differences evaluated by Kaplan-Meier analysis between groups. Patients were clustered into subgroups by consensus clustering. ESTIMATE algorithm was applied to calculate immune and stroma scores. The infiltration of immune cells was characterized by TIMER algorithm. The risk signature was constructed by multivariate Cox regression analysis. Results: Nineteen m6A regulators were highly expressed in glioma tissues. The expression of m6A regulators was associated with prognoses, grade, isocitrate dehydrogenase (IDH) status, and 1p19q status of gliomas. Two subgroups were identified by consensus clustering, in which cluster 1 was associated with favorable prognosis, high stroma and immune scores, and high immune infiltration. When the patients were divided into high risk and low risk groups based on their risk scores, we found that patients in the high risk group had poor prognoses. Besides, patients in the high risk group had a higher stroma and immune scores, and higher abundance of immune infiltration. These results were further verified in the validation cohort, which contained three independent datasets. Moreover, patients in the low risk group enjoyed better prognoses without chemoradiotherapy or single chemotherapy. Conclusion: Our study revealed that m6A regulators could predict the prognosis and therapeutic efficacy, and were also associated with the immune microenvironment in gliomas.

20.
Chemosphere ; 261: 128148, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33113665

RESUMO

Cadmium (Cd) has been confirmed to be associated with breast carcinogenesis, but the mechanism was not clarified yet. Given that epigenetic modification was speculated as underlying mechanism, we examined the differential epigenome caused by Cd in breast cancer cells. Profiles of DNA methylation, microRNA (miRNA), long non-coding RNA (lncRNA), and message RNA (mRNA) were derived from Cd-treated and untreated MCF-7 breast cancer cells by microarray. We identified 997 target genes epigenetically regulated by Cd through cross-verification with the differential epigenome and transcriptome, and 400 of them were further validated in a breast cancer cohort. Biological function analyses suggested that several pathways were involved in Cd-induced breast carcinogenesis, such as Wnt signaling, metabolism, and human papilloma virus (HPV) infection. TXNRD1 and CCT3 were further identified as the critical genes based on the degree of expression change, hazard ratio difference, and connectivity. The present study revealed that Cd epigenetically regulated several pathways involving in breast carcinogenesis, particularly the Wnt signaling and metabolic pathways, among which TXNRD1 and CCT3 might play critical roles. It was also suggested that Cd and HPV infection might jointly participate in breast tumorigenesis.


Assuntos
Neoplasias da Mama/genética , Cádmio/toxicidade , Carcinogênese/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Epigênese Genética/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Carcinogênese/genética , Metilação de DNA/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Análise Serial de Tecidos
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