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1.
Front Plant Sci ; 13: 860945, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548310

RESUMO

AtRsmD was recently demonstrated to be a chloroplast 16S rRNA methyltransferase (MTase) for the m2G915 modification in Arabidopsis. Here, its function of AtRsmD for chloroplast development and photosynthesis was further analyzed. The AtRsmD gene is highly expressed in green photosynthetic tissues. AtRsmD is associated with the thylakoid in chloroplasts. The atrsmd-2 mutant exhibited impaired photosynthetic efficiency in emerging leaves under normal growth conditions. A few thylakoid lamellas could be observed in the chloroplast from the atrsmd-2 mutant, and these thylakoids were loosely organized. Knockout of the AtRsmD gene had minor effects on chloroplast ribosome biogenesis and RNA loading on chloroplast ribosomes, but it reduced the amounts of chloroplast-encoded photosynthesis-related proteins in the emerging leaves, for example, D1, D2, CP43, and CP47, which reduced the accumulation of the photosynthetic complex. Nevertheless, knockout of the AtRsmD gene did not cause a general reduction in chloroplast-encoded proteins in Arabidopsis grown under normal growth conditions. Additionally, the atrsmd-2 mutant exhibited more sensitivity to lincomycin, which specifically inhibits the elongation of nascent polypeptide chains. Cold stress exacerbated the effect on chloroplast ribosome biogenesis in the atrsmd-2 mutant. All these data suggest that the AtRsmD protein plays distinct regulatory roles in chloroplast translation, which is required for chloroplast development and chloroplast function.

2.
J Hazard Mater ; 424(Pt A): 127268, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34583167

RESUMO

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.


Assuntos
Retardo do Crescimento Fetal , Placenta , Animais , Apoptose , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Proteína de Sequência 1 de Leucemia de Células Mieloides/genética , Gravidez , Ubiquitina-Proteína Ligases/genética
3.
J Integr Plant Biol ; 64(3): 717-730, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34958169

RESUMO

Photoperiod/temperature-sensitive genic male sterility (P/TGMS) is widely applied for improving crop production. Previous investigations using the reversible male sterile (rvms) mutant showed that slow development is a general mechanism for restoring fertility to P/TGMS lines in Arabidopsis. In this work, we isolated a restorer of rvms-2 (res3), as the male sterility of rvms-2 was rescued by res3. Phenotype analysis and molecular cloning show that a point mutation in UPEX1 l in res3 leads to delayed secretion of callase A6 from the tapetum to the locule and tetrad callose wall degradation. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis demonstrated that the tapetal transcription factor ABORTED MICROSPORES directly regulates UPEX1 expression, revealing a pathway for tapetum secretory function. Early degradation of the callose wall in the transgenic line eliminated the fertility restoration effect of res3. The fertility of multiple known P/TGMS lines with pollen wall defects was also restored by res3. We propose that the remnant callose wall may broadly compensate for the pollen wall defects of P/TGMS lines by providing protection for pollen formation. A cellular mechanism is proposed to explain how slow development restores the fertility of P/TGMS lines in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Infertilidade Masculina , Arabidopsis/fisiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fertilidade/genética , Glucanos , Infertilidade Masculina/metabolismo , Fotoperíodo , Infertilidade das Plantas/genética , Pólen/metabolismo , Temperatura
4.
Zhonghua Nan Ke Xue ; 27(8): 675-679, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34914237

RESUMO

OBJECTIVE: To analyze the effects of high-fat diet on the biological network regulation of gene expression microarray data and key proteins in mouse prostate tissue, and provide some new theoretical evidence for the mechanism of obesity inducing PCa. METHODS: From the Gene Expression Omnibus (GEO), we obtained RNAs in the prostate tissue from two groups of C57BL / 6J mice, the normal diet group (n = 5) and high-fat diet group (n = 4). Using the Gene Cloud, Gene-Cloud of Biotechnology Informs (GCBI), GenClip2.0, and Sytoscape 3.5.1, we screened differentially expressed genes, investigated protein interaction networks and biological pathways of differential genes and, from the perspective of transcriptome, explored the effects of high-fat diet on the changes of the molecular network of prostate tissue genes and the molecular biological functions possibly involved. RESULTS: A total of 134 differentially expressed genes were identified, 130 up-regulated and 4 down-regulated, mainly involved in biological functions such as chromosome organization, cell-cell signaling, small molecule biosynthesis and leukocyte activation. The Lck, Prkcb and Cd28 genes in the gene network were of high value, indicating an important relationship with protein synthesis and biological functions, the core node of the protein-protein network, and a high predictive ability of Lck and Cd28. CONCLUSIONS: The high-fat diet can induce changes in prostate tissue genes, leading to tumorigenesis.


Assuntos
Dieta Hiperlipídica , Próstata , Animais , Dieta Hiperlipídica/efeitos adversos , Redes Reguladoras de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transcriptoma
5.
Am J Mens Health ; 15(6): 15579883211067086, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34939514

RESUMO

The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Humanos , Masculino , Metanálise em Rede , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Ecotoxicol Environ Saf ; 230: 113109, 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34953275

RESUMO

Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases.

7.
Zhonghua Nan Ke Xue ; 27(10): 899-903, 2021 10 20.
Artigo em Chinês | MEDLINE | ID: mdl-34914268

RESUMO

Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method. METHODS: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. RESULTS: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. CONCLUSIONS: For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.


Assuntos
Hipogonadismo , Humanos , Hipogonadismo/diagnóstico , Hipogonadismo/genética , Masculino , Sequenciamento Completo do Exoma
8.
Mil Med Res ; 8(1): 60, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-34819142

RESUMO

BACKGROUND: The burden of kidney, bladder, and prostate cancers has changed in recent decades. This study aims to investigate the global and regional burden of, and attributable risk factors for genitourinary cancers during the past 30 years. METHODS: We extracted data of kidney, bladder, and prostate cancers from the Global Burden of Disease 2019 database, including incidence, mortality, disability-adjusted life-years (DALYs), and attributable risk factors from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to assess the changes in age-standardized incidence rate, age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). The associations between cancers burden and socio-demographic index (SDI) were also analyzed. RESULTS: Compared with 1990, the global incident cases in 2019 were higher by 154.78%, 123.34%, and 169.11% for kidney, bladder, and prostate cancers, respectively. During the 30-year study period, there was a downward trend in ASMR and ASDR for bladder cancer (EAPC = - 0.68 and - 0.83, respectively) and prostate cancer (EAPC = - 0.75 and - 0.71, respectively), but an upward trend for kidney cancer (EAPC = 0.35 and 0.12, respectively). Regions and countries with higher SDI had higher incidence, mortality, and DALYs for all three types of cancers. The burden of bladder and prostate cancers was mainly distributed among older men, whereas the burden of kidney cancer increased among middle-aged men. Smoking related mortality and DALYs decreased, but high body mass index (BMI) and high fasting plasma glucose (FPG) related mortality and DALYs increased among kidney, bladder, and prostate cancers during the study period. CONCLUSIONS: Kidney, bladder, and prostate cancers remain major global public health challenges, but with distinct trend for different disease entity across different regions and socioeconomic status. More proactive intervention strategies, at both the administrative and academic levels, based on the dynamic changes, are needed.


Assuntos
Neoplasias da Próstata , Bexiga Urinária , Idoso , Carga Global da Doença , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco
9.
Materials (Basel) ; 14(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771819

RESUMO

In this study, we measure the in-plane transport properties of high-quality Ba(Fe0.914Co0.086)2As2 single crystals. Signatures of vortex unbinding Berezinskii-Kosterlitz-Thouless (BKT) transition are shown from both the conventional approach and the Fisher-Fisher-Huse dynamic scaling analysis, in which a characteristic Nelson-Kosterlitz jump is demonstrated. We also observe a non-Hall transverse signal exactly at the superconducting transition, which is explained in terms of guided motion of unbound vortices.

10.
Future Microbiol ; 16: 1251-1259, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34674547

RESUMO

Aim: The purpose of our study was to assess the differences between HIV-negative cryptococcal meningitis (CM) patients with and without autoimmune diseases. Methods: A total of 43 CM patients with autoimmune diseases and 67 without autoimmune diseases were enrolled for analysis. Results: CM patients with autoimmune diseases had higher fever, modified Rankin Scale scores, C-reactive protein and erythrocyte sedimentation rate, but had lower rates of visual and hearing symptoms, ventriculoperitoneal shunts, MRI meningeal enhancement and amphotericin B treatment, as well as lower cerebrospinal fluid pressure and fungal counts. When divided according to gender, each group had lower intracranial pressure and higher inflammation indicators. No differences in outcomes, sequelae and mortality hazard were found. Fluconazole treatment was a prognostic factor for CM without autoimmune diseases. Conclusions: Both antifungal and anti-inflammatory therapy should be considered in CM patients with autoimmune diseases.


Assuntos
Doenças Autoimunes , Meningite Criptocócica , Antifúngicos/uso terapêutico , Doenças Autoimunes/complicações , Fluconazol/uso terapêutico , Infecções por HIV , Humanos , Meningite Criptocócica/diagnóstico , Meningite Criptocócica/tratamento farmacológico
11.
Pharmacol Res ; 174: 105955, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715330

RESUMO

Severe Coronavirus Disease 2019 (COVID-19) is characterized by numerous complications, complex disease, and high mortality, making its treatment a top priority in the treatment of COVID-19. Integrated traditional Chinese medicine (TCM) and western medicine played an important role in the prevention, treatment, and rehabilitation of COVID-19 during the epidemic. However, currently there are no evidence-based guidelines for the integrated treatment of severe COVID-19 with TCM and western medicine. Therefore, it is important to develop an evidence-based guideline on the treatment of severe COVID-19 with integrated TCM and western medicine, in order to provide clinical guidance and decision basis for healthcare professionals, public health personnel, and scientific researchers involved in the diagnosis, treatment, and care of COVID-19 patients. We developed and completed the guideline by referring to the standardization process of the "WHO handbook for guideline development", the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, and the Reporting Items for Practice Guidelines in Healthcare (RIGHT).


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Infectologia/tendências , Medicina Tradicional Chinesa/tendências , SARS-CoV-2/efeitos dos fármacos , Antivirais/efeitos adversos , COVID-19/diagnóstico , COVID-19/virologia , Consenso , Técnica Delfos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicina Baseada em Evidências/tendências , Interações Hospedeiro-Patógeno , Humanos , Gravidade do Paciente , SARS-CoV-2/patogenicidade , Resultado do Tratamento
12.
Ecotoxicol Environ Saf ; 224: 112632, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34411824

RESUMO

Gestational exposure to environmental Cd caused placental angiogenesis impairment and fetal growth restriction (FGR). However, its mechanism remained unclear. This study was to investigate the effects of Cd exposure during pregnancy on placental angiogenesis and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 8 with or without melatonin (MT) (5.0 mg/kg), an anti-endoplasmic reticulum stress agent, from GD7 to GD15. Human primary placental trophoblasts and JEG-3 cells were stimulated using CdCl2 (20 µM) after MT (1 mM) preprocessing. We firstly found MT treatment obviously mitigated environmental Cd-induced placental angiogenesis disorder and reduction of the VEGF-A level. Mechanistically, MT reversed environmental Cd-downregulated the protein expression of VEGF-A via inhibiting glucocorticoid receptor (GR) activation. Notably, our data showed MT treatment antagonized Cd-activated GC/GR signaling via blocking PERK signaling and thereby upregulated VEGF-A and 11ß-HSD2 protein expression. Based upon the population case-control study, the levels of VEGF-A and 11ß-HSD2 protein in small-for-gestational-age placentae were significantly reduced when compared to appropriate-for-gestational-age placentae. Overall, environmental Cd exposure during gestation impaired placental angiogenesis via PERK-regulated GC/GR signaling in placental trophoblasts. Our findings will provide a basis for prevention and treatment of placental impairments and fetal growth restriction caused by environment toxicants in future.

13.
Am J Mens Health ; 15(4): 15579883211036786, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34330182

RESUMO

The objective of this study is to provide comprehensive and up-to-date estimates on the disease burden of BPH in 204 countries and territories between 1990 and 2019. Data about incidence, year lived with disability (YLD), and their age-standardized rates (ASRs) for 21 regions, 5 Socio-demographic Index (SDI) quintiles, 204 countries and territories, and 12 age categories from 1990 to 2019 were obtained from the Global Burden of Disease 2019 study. Estimated annual percentage changes (EAPCs) of the ASRs and the associations between SDI and the ASRs were estimated. The effects of population growth, population aging, and age-specific rate on the changes in the absolute numbers of incidence and YLD were quantified. Globally, there were 11.26 million (95% uncertainty interval [UI]: 8.79, 14.46) new cases and 1.86 million (95%UI: 1.13, 2.78) YLD due to BPH in 2019. The global ASRs of incidence (EAPC: -0.031, 95% CI: -0.050, -0.012) and YLD (EAPC: -0.058, 95% CI: -0.084, -0.031) decreased slightly from 1990 to 2019, whereas the absolute numbers increased dramatically from 1990 (incidence by 105.7% and YLD by 110.6%), mainly driven by the population growth (53.5% for incidence and 54.4% for YLD) and population aging (55.7% for incidence and 63.2% for YLD). The burden of BPH varied markedly among different regions, socioeconomic status, and countries. As the population is growing and aging, great efforts are required to develop effective prevention, treatment and management strategies to meet the high and increasing burden of BPH worldwide.


Assuntos
Pessoas com Deficiência/estatística & dados numéricos , Carga Global da Doença/estatística & dados numéricos , Hiperplasia Prostática/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Incidência , Expectativa de Vida , Masculino , Pessoa de Meia-Idade , Prevalência , Anos de Vida Ajustados por Qualidade de Vida , Fatores Socioeconômicos
14.
Oncol Rep ; 46(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34278491

RESUMO

Serine proteinase inhibitor B9 (serpin B9) is a member of the serine protease inhibitor superfamily, which is widely found in animals, plants and microorganisms. Serpin B9 has been reported to protect cells from the immune­killing effect of granzyme B (GrB) released by lymphocytes. In recent years, an increasing number of studies have indicated that serpin B9 is involved in tumour apoptosis, immune evasion, tumorigenesis, progression, metastasis, drug resistance and even in maintaining the stemness of cancer stem cells (CSCs). Moreover, according to clinical studies, serpin B9 has been demonstrated to be significantly associated with the development of precancerous lesions, a poor prognosis and ineffective therapies, suggesting that serpin B9 may be a potential target for cancer treatment and an indicator of cancer diagnosis; thus, it has begun to attract increased attention from scholars. The present review concisely described the structure and biological functions of the serpin superfamily and serpin B9. In addition, related research on serpins in cancer is discussed in order to provide a comprehensive understanding of the role of serpin B9 in cancer, as well as its clinical significance for cancer diagnosis and prognosis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Inibidores de Serino Proteinase/fisiologia , Serpinas/metabolismo , Serpinas/fisiologia , Animais , Antineoplásicos/farmacologia , Apoptose , Granzimas/metabolismo , Humanos , Sistema Imunitário , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/terapia , Células-Tronco Neoplásicas/citologia , Prognóstico
15.
Oncol Rep ; 45(5)2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33760175

RESUMO

Hypoxia is a common phenomenon during tumorigenesis and tumour development. In recent years, studies have found that hypoxia­inducible factor (HIF)­2α, also referred to as endothelial PAS domain protein­1, plays an important role in tumours. HIF­2α is an important oncogene and a critical prognostic indicator in non­small cell lung cancer. However, no unified conclusion can be drawn concerning HIF­2α and small cell lung cancer, since few studies to date have focused on their association. An increasing number of studies have confirmed that HIF­2α is involved in tumorigenesis, cell proliferation, angiogenesis, metastasis, drug resistance and radiotherapy failure in lung cancer. Of note, HIF­2α plays a crucial role in lung cancer to maintain cancer cell stemness. Based on the importance of HIF­2α in lung cancer, HIF­2α­targeted therapy has been attracting increasing attention. Although this strategy currently appears to be promising in vitro, it has never been assessed as a therapy for lung cancer. The aim of the present review was to summarize the contribution of HIF­2α to various aspects of lung cancer, as well as its potential as targeted therapy.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neovascularização Patológica/genética , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Quimiorradioterapia/métodos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Terapia de Alvo Molecular/métodos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Prognóstico , Intervalo Livre de Progressão , Tolerância a Radiação/genética
16.
Redox Biol ; 40: 101854, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33454563

RESUMO

Gestational exposure to environmental stress induces fetal growth restriction (FGR), and thereby increasing the risk of infant death and chronic noncommunicable diseases in adults. However, the mechanism by which environmental stress induces FGR remains unclear. Based on case-control study, we found that the reduced level of melatonin (MT), a major secretory product from the pineal gland, was observed in placentae of FGR. This work was to investigate the protective effect of MT on environmental stress-caused FGR and its mechanisms. We used cadmium (Cd) as an environmental stressor to stimulate pregnant mice and thereby establishing a FGR model. The data showed that maternal Cd exposure lowered the P4 concentration in maternal sera, placentae and amniotic fluid, and caused FGR. Correspondingly, the expression of CYP11A1, a critical P4 synthase, was markedly downregulated in Cd-treated placentae. Simultaneously, Cd triggered BNIP3-dependent mitophagy in placental trophoblasts, as determined by the degradation of mitochondrial proteins, including HSP60 and COX IV, and the accumulation of puncta representing co-localization of TOM20 with LC3B or BNIP3 with LC3B. Based on our case-control study, we also found that activated BNIP3-dependent mitophagy and P4 synthesis inhibition occurred in SGA placentae. Most importantly, BNIP3 siRNA reversed Cd-induced P4 synthesis suppression in human placental trophoblasts. It is noteworthy that MT alleviated Cd-caused P4 synthesis suppression and FGR via antagonizing BNIP3-dependent mitophagy in placental trophoblasts. Further results confirmed that MT attenuated Cd-triggered BNIP3-dependent mitophagy via blocking GCN2/ATF4 signaling. Amusingly, Cd triggered oxidative stress and then activating GCN2/ATF4 signaling in placental trophoblasts. As expected, MT obviously suppressed Cd-caused reactive oxygen species (ROS) release. In the present study, we propose a neoteric mechanism by which MT protects against environmental stress-impaired P4 synthesis and fetal growth via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts. As above, MT is a potential therapeutic agent antagonizing environmental stress-induced developmental toxicity.


Assuntos
Melatonina , Trofoblastos , Fator 4 Ativador da Transcrição , Adulto , Animais , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal , Humanos , Proteínas de Membrana/genética , Camundongos , Proteínas Mitocondriais , Mitofagia , Placenta , Gravidez , Proteínas Proto-Oncogênicas/genética , Espécies Reativas de Oxigênio
18.
J Hazard Mater ; 401: 123438, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-32763717

RESUMO

Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress.


Assuntos
Cádmio , Fator A de Crescimento do Endotélio Vascular , Animais , Cádmio/toxicidade , Estudos de Casos e Controles , Exposição Ambiental , Feminino , Desenvolvimento Fetal , Camundongos , Placenta , Gravidez , Trofoblastos , Fator A de Crescimento do Endotélio Vascular/genética
19.
Environ Int ; 147: 106319, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33348103

RESUMO

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.


Assuntos
Retardo do Crescimento Fetal , Trofoblastos , Animais , Cádmio/toxicidade , Estudos de Casos e Controles , Feminino , Retardo do Crescimento Fetal/induzido quimicamente , Camundongos , Mitofagia , Placenta , Gravidez
20.
Front Oncol ; 11: 796975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35127507

RESUMO

OBJECTIVE: Limited attention has been paid to abnormal blood and urine test results for patients with bladder cancer. The present study aimed to identify whether blood and urine parameters are associated with bladder cancer. METHODS: We used a case-control design and matched each patient with bladder cancer with three healthy controls of the same age and sex. Univariate conditional logistic regression was used to calculate the crude and adjusted odds ratio (OR) and its 95% CI. Multivariate conditional logistic regression was performed for confounders adjustment, and Spearman's correlation coefficient was used to assess the correlation between tumor T stages and urine parameters. RESULTS: Patients with bladder cancer (n = 360) and controls (n = 1050) were recruited. In the univariate conditional logistic analysis, higher urine pH was associated with a decreased risk of bladder cancer (OR = 0.67, 95% CI = 0.57-0.78), while higher values of urine protein (OR = 4.55, 95% CI = 3.36-6.15), urine glucose (OR = 1.56, 95% CI = 1.18-2.05), and urine occult blood (OR = 4.27, 95% CI = 3.44-5.29) were associated with an increased risk of bladder cancer. After adjustment for body mass index, fasting blood glucose, hypertension, red blood cells, white blood cells, lymphocytes, neutrophils, and platelets, significance still remained for urine pH (OR = 0.68, 95% CI = 0.53-0.88), urine protein (OR = 1.97, 95% CI = 1.21-3.19), urine glucose (OR = 2.61, 95% CI = 1.39-4.89), and urine occult blood (OR = 3.54, 95% CI = 2.73-4.58). CONCLUSION: This study indicated that lower urine pH and higher values of urine protein, urine glucose, and urine occult blood might be risk factors for bladder cancer.

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