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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(3): 284-288, 2024 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-38448015

RESUMO

OBJECTIVE: To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Genetic epilepsy with febrile seizures plus (GEFS+). METHODS: Three GEFS+ probands and their pedigree members presented at the Children's Hospital of Zhengzhou University from January 2020 to December 2021 were selected as the study subjects. Clinical data of the pedigrees were collected. Whole exome sequencing was carried out for the probands, and Sanger sequencing was used to verify the candidate variants. RESULTS: Proband 1 was a 3-year-and-2-month-old male with febrile seizure plus. His father, two aunts, grandmother, aunt grandmother, uncle grandfather, and paternal great-grandmother also had onset of febrile seizures at 1 ~ 2 years of age with remission before 6 years old. Proband 2 was a 1-year-and-4-month-old male with complex febrile seizure. His mother, maternal uncle, and maternal grandmother also had febrile seizures before 5 ~ 6 years of age. Proband 3 was a 3-year-and-11-month-old male with febrile seizure plus. His father and grandfather also had febrile seizures plus with remission at 7 ~ 8 years of age. Genetic testing revealed that proband 1 had harbored a paternally derived heterozygous SCN1A: c.1613T>C variant, proband 2 had harbored a maternally derived heterozygous SCN1A: c.2804A>G variant, and proband 3 had harbored a paternally derived heterozygous SCN1A: c.1271T>C variant. All of the three variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (PM1+PM2_Supporting+PP1+PP3+PP4). CONCLUSION: The c.1613T>C, c.2804A>G and c.1271T>C variants probably underlay the pathogenesis of GEFS+ in these pedigrees.


Assuntos
Epilepsia , Convulsões Febris , Criança , Feminino , Humanos , Lactente , Masculino , China , Mães , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Linhagem , Convulsões Febris/genética , Pré-Escolar
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(3): 302-307, 2023 Mar 15.
Artigo em Chinês | MEDLINE | ID: mdl-36946167

RESUMO

OBJECTIVES: To study the clinical features of children with autoimmune encephalitis (AE) secondary to epidemic encephalitis B (EEB). METHODS: A retrospective analysis was performed on the medical data of five children with EEB with "bipolar course" who were treated in Children's Hospital Affiliated to Zhengzhou University from January 2020 to June 2022. RESULTS: Among the five children, there were three boys and two girls, with a median age of onset of 7 years (range 3 years 9 months to 12 years) and a median time of 32 (range 25-37) days from the onset of EEB to the appearance of AE symptoms. The main symptoms in the AE stage included dyskinesia (5/5), low-grade fever (4/5), mental and behavioral disorders (4/5), convulsion (2/5), severe disturbance of consciousness (2/5), and limb weakness (1/5). Compared with the results of cranial MRI in the acute phase of EEB, the lesions were enlarged in 3 children and unchanged in 2 children showed on cranial MRI in the AE stage. In the AE stage, four children were positive for anti-N-methyl-D-aspartate receptor antibody (one was also positive for anti-γ-aminobutyric acid type B receptor antibody), and one was negative for all AE antibodies. All five children in the AE stage responded to immunotherapy and were followed up for 3 months, among whom one almost recovered and four still had neurological dysfunction. CONCLUSIONS: EEB can induce AE, with anti-N-methyl-D-aspartate receptor encephalitis as the most common disease. The symptoms in the AE stage are similar to those of classical anti-N-methyl-D-aspartate receptor encephalitis. Immunotherapy is effective for children with AE secondary to EEB, and the prognosis might be related to neurological dysfunction in the acute phase of EEB.


Assuntos
Encefalite Antirreceptor de N-Metil-D-Aspartato , Encefalite por Arbovirus , Doença de Hashimoto , Masculino , Feminino , Humanos , Criança , Recém-Nascido , Estudos Retrospectivos , Doença de Hashimoto/complicações , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/terapia
3.
J Sci Food Agric ; 102(15): 6868-6876, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35642942

RESUMO

BACKGROUND: As a potential selenium-enriched crop, it is of great significance to study the selenium application of Tartary buckwheat. Therefore, to study the effects of selenium application concentration, variety, selenium application period and method on the grain selenium content and yield of Tartary buckwheat, an orthogonal experimental design was used to carry out field experiments in the Jinzhong and Northwest Shanxi ecological regions at the same time. Heifeng 1 and Jinqiao 2 were applied at the branching stage and flowering stage in the Jinzhong, and Heifeng 1 and Jinqiao 6 were applied at the early flowering stage and peak flowering stage in the Northwest Shanxi with different concentrations of sodium selenite (0, 1.37, 2.74, 5.48, 8.22, 12.33, 18.495, 27.7425 g hm-2 ) by foliar spraying and soil application. RESULTS: The results showed that the selenium content in Tartary buckwheat grains was positively correlated with the selenium application concentration and increased with increasing selenium application concentration, while the yield of Tartary buckwheat first increased and then decreased with the selenium application concentration. The grain selenium content and yield of Tartary buckwheat were affected by the selenium application concentration, variety and application method. CONCLUSION: The most effective selenium biofortification program was spraying 2.32 g hm-2 sodium selenite on the leaves of Heifeng 1 at the early flowering stage in the Jinzhong. In the Northwest Shanxi, spraying 11.01 g hm-2 sodium selenite on the leaves of Jinqiao 6 at the flowering stage was the most effective selenium biofortification program. © 2022 Society of Chemical Industry.


Assuntos
Fagopyrum , Selênio , Selênio/análise , Fagopyrum/química , Selenito de Sódio/análise , Projetos de Pesquisa , Folhas de Planta/química , Grão Comestível
4.
Ecotoxicology ; 26(7): 1002-1009, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28685415

RESUMO

Beta-cypermethrin has long been recommended as an effective pesticide to control the soybean aphid, Aphis glycines Matsumura, a serious pest in soybean crops. Besides acute toxicity, it leads to changes in life history traits of A. glycines, notably its reproductive potential. This study has assessed the effects of five sublethal concentrations (0.625, 1.25, 2.5, 5 and 10 µg/L) of beta-cypermethrin on different life history traits of A. glycines. Exposure to these concentrations caused shorter oviposition period and reduced adult longevity. The strongest stimulatory effect on aphid reproduction was achieved when exposed to a higher sublethal beta-cypermethrin concentration (5 µg/L). Net reproduction rate (R 0 ), intrinsic rate of increase (r m ) and finite rate of increase (λ) were significantly higher than that of the control, increasing by 20.58, 4.89 and 2.06%, respectively. We found no significant difference in mean generation time (T) between the treatment of 5 µg/L beta-cypermethrin and the control. However, when the concentration increased to 10 µg/L, the reproduction behavior was restrained and the mean generation time (T) was shortened, resulting in significant decrease in R 0 and T by 16.58 and 3.83%, respectively. In conclusion, a sublethal concentration (5 µg/L) of beta-cypermethrin triggered the strongest hormesis on A.glycines, thus providing valuable knowledge on the sublethal effects of this insecticide on soybean aphids. Hormesis may be one of the mechanisms underlying pest resurgences, and better knowledge would enable a more effective use of insecticides in Integrated Pest Management programs.


Assuntos
Afídeos/fisiologia , Inseticidas/toxicidade , Piretrinas/toxicidade , Testes de Toxicidade , Animais , Afídeos/efeitos dos fármacos , Hormese/efeitos dos fármacos , Reprodução/efeitos dos fármacos , Glycine max
5.
Mol Cell Neurosci ; 52: 38-50, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23026563

RESUMO

Many neuropsychiatric conditions have a common set of neurological substrates associated with the integration of sensorimotor processing. The teneurins are a recently described family of proteins that play a significant role in visual and auditory development. Encoded on the terminal exon of the teneurin genes is a family of bioactive peptides, termed teneurin C-terminal associated peptides (TCAP), which regulate mood-disorder associated behaviors. Thus, the teneurin-TCAP system could represent a novel neurological system underlying the origins of a number of complex neuropsychiatric conditions. However, it is not known if TCAP-1 exerts its effects as part of a direct teneurin function, whereby TCAP represents a functional region of the larger teneurin protein, or if it has an independent role, either as a splice variant or post-translational proteolytic cleavage product of teneurin. In this study, we show that TCAP-1 can be transcribed as a smaller mRNA transcript. After translation, further processing yields a smaller 15 kDa protein containing the TCAP-1 region. In the mouse hippocampus, immunoreactive (ir) TCAP-1 is exclusively localized to the pyramidal layers of the CA1, CA2 and CA3 regions. Although the localization of TCAP and teneurin in hippocampal regions is similar, they are distinct within the cell as most ir-teneurin is found at the plasma membrane, whereas ir-TCAP-1 is predominantly found in the cytosol. Moreover, in mouse embryonic hippocampal cell culture, FITC-labeled TCAP-1 binds to the plasma membrane and is taken up into the cytosol via dynamin-dependent caveolae-mediated endocytosis. Our data provides novel evidence that TCAP-1 is structurally and functionally distinct from the larger teneurins.


Assuntos
Hipocampo/metabolismo , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/metabolismo , Células Piramidais/metabolismo , Sequência de Aminoácidos , Animais , Northern Blotting , Western Blotting , Imunofluorescência , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Biossíntese de Proteínas , Tenascina/química , Tenascina/metabolismo , Transcrição Gênica
6.
Luminescence ; 29(8): 1066-73, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24851824

RESUMO

By taking advantage of microflow injection chemiluminescence analysis, we developed a distinctive microfluidic bioassay method based on G-Quadruplex DNAzyme-enhanced chemiluminescence for the determination of K(+) in human serum. AGRO100, the G-rich oligonucleotide with high hemin binding affinity was primarily selected as a K(+) recognition element. In the presence of K(+), AGRO100 folded into G-quadruplex and bound hemin to form DNAzyme, which catalyzed the oxidation of luminol by H2 O2 to produce chemiluminescence. The intensity of chemiluminescence increased with the K(+) concentration. In the study, the DNAzyme showed both long-term stability and high catalytic activity; other common cations at their physiological concentration did not cause notable interference. With only 6.7 × 10(-13) mol of AGRO100 consumption per sample, a linear response of K(+) ranged from 1 to 300 µmol/L, the concentration detection limit 0.69 µmol/L (S/N = 3) and the absolute detection limit 1.38 × 10(-12) mol were obtained. The precision of 10 replicate measurements of 60 µmol/L K(+) was found to be 1.72% (relative standard deviation). The accuracy of the method was demonstrated by analyzing real human serum samples.


Assuntos
Análise de Injeção de Fluxo/métodos , Quadruplex G , Medições Luminescentes/métodos , Técnicas Analíticas Microfluídicas/métodos , Potássio/sangue , Aptâmeros de Nucleotídeos , DNA Catalítico/química , DNA Catalítico/metabolismo , Desenho de Equipamento , Análise de Injeção de Fluxo/instrumentação , Hemina/química , Humanos , Peróxido de Hidrogênio/metabolismo , Limite de Detecção , Medições Luminescentes/instrumentação , Luminol/química , Luminol/metabolismo , Técnicas Analíticas Microfluídicas/instrumentação , Oligodesoxirribonucleotídeos/metabolismo , Reprodutibilidade dos Testes
7.
Mol Genet Genomic Med ; 12(4): e2432, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38588043

RESUMO

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with Polyglucosan body myopathy 1 (PGBM1) caused by a novel compound heterozygous variant in the RBCK1 gene. METHODS: The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing. RESULTS: Through whole-exome sequencing, we found that there were c.919G>T; p. (Glu307*) and c.723_730dup; p. (Glu244fs) variants of the RBCK1 gene in the patient, inherited from his parents, constituting a compound heterozygous variation. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), the two variants were rated as pathogenic, but there were no comparable cases. Previous literature reported 24 patients with RBCK1 gene variants, involving a total of 20 myocardial and 18 skeletal muscle cases. CONCLUSIONS: The patient was twice diagnosed with cardiac insufficiency, neglecting the usual manifestations of muscle weakness, resulting in misdiagnosis. Later, novel variants in the RBCK1 gene were discovered through whole-exome sequencing, and symptomatic treatment was given after diagnosis. The importance of whole-exome sequencing technology in disease diagnosis and genetic counseling was emphasized.


Assuntos
Doenças Musculares , Humanos , Doenças Musculares/genética , Glucanos , Músculo Esquelético , Miocárdio , Fatores de Transcrição , Ubiquitina-Proteína Ligases
8.
Int J Cardiol ; 411: 132270, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880423

RESUMO

BACKGROUND: The purpose of this study was to analyse the association between stannum exposure during pregnancy and congenital heart diseases in offspring. METHODS: Based on a prospective birth cohort study conducted in Gansu Maternal and Child Health Hospital from 2010 to 2012, 14,359 pregnant women were followed up using a nested case-control study method. 97 pregnant women whose offspring were diagnosed with CHDs were used as the case group, and 194 pregnant women whose offspring did not suffer from congenital heart diseases were used as the control group in a ratio of 1:2 according to their age and place of birth. Inductively coupled plasma mass spectrometry was used to determine elemental stannum in blood samples from pregnant women hospitalized for delivery and in fetal cord blood samples. Multifactorial logistic regression analysis was used to assess the association between stannum and offspring CHDs. RESULTS: There was a moderate positive correlation between the concentration of stannum in pregnant women's blood and that in umbilical cord blood. A higher concentrations of maternal blood stannum level was associated with a greater risk of CHDs (aOR 3.409, 95%CI 1.785-6.826), isolated CHDs (aOR 4.044, 95%CI 1.803-9.070), multiple CHDs (aOR 2.625, 95%CI 1.137-6.061), patent ductus arteriosus (aOR 2.882, 95%CI 1.443-5.756), atrial septal defects (aOR 3.067, 95%CI 1.406-6.690), ventricular septal defects (aOR 7.414, 95%CI 1.414-38.874). There was a correlation between the maternal and cord blood sample suggesting stannum crosses the placenta.

9.
BMJ Open ; 14(3): e076127, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485488

RESUMO

INTRODUCTION: Breast cancer-related lymphedema (BCRL) is a common postoperative complication of breast cancer. It develops in a chronic and vicious cycle. Once lymphedema occurs, it cannot be cured and bring serious physiological, psychological, social and economic burden to patients. Upper limb functional exercises are an effective and convenient intervention for managing lymphedema. However, the optimal exercise sequence remains unclear. Therefore, we aim to compare the effects of exercise sequences under the guidance of commonly used exercise sequences and lymphatic flow theory. METHODS: An exploratory randomised controlled cross-over trial will be conducted. 32 patients with BCRL are randomly allocated into two groups (group A and group B). Group A patients will perform functional exercise from wrist joint to shoulder joint, and the exercise direction of group B is opposite to that of group A, that is, from shoulder joint to wrist joint end. Exercise time is once a day, each 20-30 min, for 2 weeks. After 2 weeks of washout period, A and B groups of exchange exercise sequences (exercise frequency and duration unchanged). The primary outcome is upper limb circumference, and secondary outcomes are upper limb function and lymphedema symptoms. ETHICS AND DISSEMINATION: This study protocol is presented in accordance with the Standard Protocol Items: Recommendations for Interventional Trials guidelines. All participants will sign a written informed consent. The research ethics regional committee of Shanghai Seventh People's Hospital has approved the study. Regardless of the outcome of this study, the results will be published in open-access journals to ensure public access. TRIAL REGISTRATION NUMBER: ChiCTR2200066463.


Assuntos
Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Linfedema , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Estudos Cross-Over , China , Linfedema/etiologia , Linfedema/terapia , Linfedema Relacionado a Câncer de Mama/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
Int J Radiat Oncol Biol Phys ; 118(5): 1308-1314, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38104868

RESUMO

PURPOSE: Small cell lung cancer (SCLC) is an aggressive and lethal form of lung cancer and the overall 5-year survival (OS) for patients is a dismal 7%. Radiation therapy (RT) provides some benefit for selected patients with SCLC but could be improved with radiosensitizing agents. In this study, we identified novel radiosensitizers for SCLC by a CRISPR-Cas9 screen and evaluated the efficacy of ATM inhibitor AZD1390 as a radiosensitizer of SCLC. METHODS AND MATERIALS: We transduced the SCLC cell line SBC5 with a custom CRISPR sgRNA library focused on druggable gene targets and treated cells with RT. Cells collected at multiple timepoints were subjected to next-generation sequencing. We determined radiosensitization both in vitro with cell lines assessed by short-term viability and clonogenic assays, and in vivo mouse models by tumor growth delay. Pharmacodynamic effects of AZD1390 were quantified by ATM-Ser1981 phosphorylation, and RT-induced DNA damage by comet assay. RESULTS: Using a CRISPR dropout screen, we identified multiple radiosensitizing genes for SCLC at various timepoints with ATM as a top determinant gene for radiosensitivity. Validation by ATM knockout (KO) demonstrated increased radiosensitivity by short-term viability assay (dose modification factor [DMF]50 = 3.25-3.73 in SBC5 ATM-KO) and clonogenic assays (DMF37 1.25-1.65 in SBC5 ATM-KO). ATM inhibition by AZD1390 effectively abrogated ATM Ser1981 phosphorylation in SCLC cell lines and increased RT-induced DNA damage. AZD1390 synergistically increased the radiosensitivity of SCLC cell lines (cell viability assay: SBC5 DMF37 = 2.19, SHP77 DMF37 = 1.56, H446 DMF37 = 3.27, KP1 DMF37 = 1.65 at 100nM; clonogenic assay: SBC5 DMF37 = 4.23, H1048 DMF37 = 1.91), and in vivo murine syngeneic, KP1, and patient-derived xenograft (PDX) models, JHU-LX108 and JHU-LX33. CONCLUSIONS: In this study, we demonstrated that genetically and pharmacologically (AZD1390) inhibiting ATM markedly enhanced RT against SCLC, providing a novel pharmacologically tractable radiosensitizing strategy for patients with SCLC.


Assuntos
Neoplasias Pulmonares , Piridinas , Quinolonas , Radiossensibilizantes , Carcinoma de Pequenas Células do Pulmão , Humanos , Animais , Camundongos , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/radioterapia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , RNA Guia de Sistemas CRISPR-Cas , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Linhagem Celular Tumoral , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo
11.
Environ Sci Pollut Res Int ; 30(21): 60777-60804, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37039920

RESUMO

To achieve low-carbon development of industrial land in China, it is important to coordinate the conflicts of interest among stakeholders in the process of land expropriation and utilization. However, the complex interaction mechanism and influencing factors among stakeholders make it difficult to achieve the goal under the Chinese decentralization and unique land development pattern. To solve these problems, this paper first analyzes the four main stakeholders' conflicts of interest in the process of land expropriation and utilization, that is, the central government, local government, peasant, and enterprise. Then, we construct two evolutionary game models to examine the dynamic changes of stakeholders' different strategies and take the Beijing-Tianjin-Hebei region as an example to compare the impacts of factors on strategies under different conditions using simulation analysis. The research shows that under the Chinese decentralization, adjusting the action strengths of different stakeholders can have different effects on system equilibrium. In terms of the central government's reward and penalty, increasing the reward and penalty for local government will shorten the time of system equilibrium to a different degree, and there is little difference between the effects of political and economic penalties. Interestingly, increasing the incentives for peasants cannot promote the system equilibrium in advance. In addition, the key to local governments' decision on illegal land expropriation lies in benefits rather than costs, and investment in low-carbon technology reform with positive externalities is easier to control than investment in economic production with negative externalities associated with pollution emissions.


Assuntos
Carbono , Desenvolvimento Econômico , Pequim , Carbono/análise , China , Política
12.
Foods ; 12(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37048175

RESUMO

Tartary buckwheat is a common functional food. Its grains are rich in flavonoids and phenols. The rapid measurement of flavonoids and phenols in buckwheat grains is of great significance in promoting the development of the buckwheat industry. This study, based on multiple scattering correction (MSC), standardized normal variate (SNV), reciprocal logarithm (Lg), first-order derivative (FD), second-order derivative (SD), and fractional-order derivative (FOD) preprocessing spectra, constructed hyperspectral monitoring models of total flavonoids content and total phenols content in tartary buckwheat grains. The results showed that SNV, Lg, FD, SD, and FOD preprocessing had different effects on the original spectral reflectance and that FOD can also reflect the change process from the original spectrum to the integer-order derivative spectrum. Compared with the original spectrum, MSC, SNV, Lg, FD, and SD transformation spectra can improve the correlation between spectral data and total flavonoids and total phenols in varying degrees, while the correlation between FOD spectra of different orders and total flavonoids and total phenols in grains was different. The monitoring models of total flavonoids and total phenols in grains based on MSC, SNV, Lg, FD, and SD transformation spectra achieved the best accuracy under SD and FD transformation, respectively. Therefore, this study further constructed monitoring models of total flavonoids and total phenols content in grains based on the FOD spectrum and achieved the best accuracy under 1.6 and 0.6 order derivative preprocessing, respectively. The R2c, RMSEc, R2v, RMSEv, and RPD were 0.8731, 0.1332, 0.8384, 0.1448, and 2.4475 for the total flavonoids model, and 0.8296, 0.2025, 0.6535, 0.1740, and 1.6713 for the total phenols model. The model can realize the rapid measurement of total flavonoids content and total phenols content in tartary buckwheat grains, respectively.

13.
Emerg Microbes Infect ; 12(1): e2143283, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36377297

RESUMO

Over one billion people have received 2-3 dosages of an inactivated COVID-19 vaccine for basic immunization. Whether a booster dose should be delivered to protect against the Omicron variant and its sub-lineages, remains controversial. Here, we tested different vaccine platforms targeting the ancestral or Omicron strain as a secondary booster of the ancestral inactivated vaccine in mice. We found that the Omicron-adapted inactivated viral vaccine promoted a neutralizing antibody response against Omicron in mice. Furthermore, heterologous immunization with COVID-19 vaccines based on different platforms remarkably elevated the levels of cross- neutralizing antibody against Omicron and its sub-lineages. Omicron-adapted vaccines based on heterologous platforms should be prioritized in future vaccination strategies to control COVID-19.


Assuntos
COVID-19 , Vacinas , Camundongos , Animais , Humanos , Anticorpos Neutralizantes , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Amplamente Neutralizantes , Anticorpos Antivirais
14.
Signal Transduct Target Ther ; 8(1): 366, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37743418

RESUMO

With the continuous in-depth study of the interaction mechanism between viruses and hosts, the virus has become a promising tool in cancer treatment. In fact, many oncolytic viruses with selectivity and effectiveness have been used in cancer therapy. Human enterovirus is one of the most convenient sources to generate oncolytic viruses, however, the high seroprevalence of some enteroviruses limits its application which urges to exploit more oncolytic enteroviruses. In this study, coxsackievirus B5/Faulkner (CV-B5/F) was screened for its potential oncolytic effect against non-small cell lung cancers (NSCLCs) through inducing apoptosis and autophagy. For refractory NSCLCs, DNA-dependent protein kinase (DNA-PK) or ataxia telangiectasia mutated protein (ATM) inhibitors can synergize with CV-B5/F to promote refractory cell death. Here, we showed that viral infection triggered endoplasmic reticulum (ER) stress-related pro-apoptosis and autophagy signals, whereas repair for double-stranded DNA breaks (DSBs) contributed to cell survival which can be antagonized by inhibitor-induced cell death, manifesting exacerbated DSBs, apoptosis, and autophagy. Mechanistically, PERK pathway was activated by the combination of CV-B5/F and inhibitor, and the irreversible ER stress-induced exacerbated cell death. Furthermore, the degradation of activated STING by ERphagy promoted viral replication. Meanwhile, no treatment-related deaths due to CV-B5/F and/or inhibitors occurred. Conclusively, our study identifies an oncolytic CV-B5/F and the synergistic effects of inhibitors of DNA-PK or ATM, which is a potential therapy for NSCLCs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Vírus Oncolíticos , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Estudos Soroepidemiológicos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Apoptose/genética , Vírus Oncolíticos/genética , DNA
15.
Am J Physiol Endocrinol Metab ; 303(6): E740-51, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22811470

RESUMO

Insulin therapy using insulin detemir (d-INS) has demonstrated weight-sparing effects compared with other insulin formulations. Mechanisms underlying these effects, however, remain largely unknown. Here we postulate that the intestinal tissues' selective preference allows d-INS to exert enhanced action on proglucagon (Gcg) expression and the production of glucagon-like peptide (GLP)-1, an incretin hormone possessing both glycemia-lowering and weight loss effects. To test this hypothesis, we used obese type 2 diabetic db/db mice and conducted a 14-day intervention with daily injection of a therapeutic dose of d-INS or human insulin (h-INS) in these mice. The body weight of the mice after 14-day daily injection of d-INS (5 IU/kg) was decreased significantly compared with those injected with the same dose of h-INS or saline. The weight-sparing effect of d-INS was associated with significantly elevated circulating levels of total GLP-1 and reduced food intake. Histochemistry analysis demonstrated that d-INS induced rapid phosphorylation of protein kinase B (Akt) in the gut L cells of normal mice. Western blotting showed that d-INS stimulated Akt activation in a more rapid and enhanced fashion in the mouse distal ileum compared with those by h-INS. In vitro investigation in primary fetal rat intestinal cell (FRIC) cultures showed that d-INS increased Gcg mRNA expression as determined by Northern blotting and real-time RT-PCR. Consistent with these in vivo investigations, d-INS significantly increased GLP-1 secretion in FRIC cultures. Consistently, d-INS was also shown to induce rapid phosphorylation of Akt in the clonal gut cell line GLUTag. Furthermore, d-INS increased ß-catenin phosphorylation, its nuclear translocation, and enhanced cAMP response element-binding protein (CREB) phosphorylation in a phosphatidylinositol 3-kinase and/or mitogen-activated protein kinase kinase/extracellular signal-regulated kinase-sensitive manner. We suggest that the weight-sparing benefit of d-INS in mice is related to its intestinal tissues preference that leads to profound stimulation of Gcg expression and enhanced GLP-1 secretion in intestinal L cells, potentially involving the activation of insulin/ß-catenin/CREB signaling pathways.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Mucosa Intestinal/efeitos dos fármacos , Proglucagon/metabolismo , beta Catenina/metabolismo , Animais , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/agonistas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feto/citologia , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hipoglicemiantes/farmacologia , Insulina Detemir , Insulina de Ação Prolongada/farmacologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Células L , Camundongos , Camundongos Mutantes , Obesidade/complicações , Obesidade/prevenção & controle , Especificidade de Órgãos , Fosforilação/efeitos dos fármacos , Proglucagon/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , beta Catenina/agonistas
16.
Materials (Basel) ; 15(7)2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35408009

RESUMO

In order to improve the initial color and the long-term heat stability of super-transparent polyvinyl chloride (PVC), a series of composite heat stabilizers consisting of unsaturated Zn oleate and uracil derivatives have been designed in this paper. The uracil derivatives are 1,3-dimethyl-6-amino-uracil (DAU) and 6,6'-diamino-1,1',3,3'-tetramethyl-5,5'-(ethylidene)bisuracil (OSU). The static thermal stability, dynamic thermal stability, and transparency were used to evaluate the properties of the stabilized transparent PVC sheets. The results indicate that the compatibility between the stabilizer and PVC was greatly enhanced by introducing an unsaturated long-chain Zn oleate and a long alkyl chain bisuracil derivative. Through the thermal discoloration test, the best ratio of DAU/zinc oleate (DAU/Zn) and OSU/zinc oleate (OSU/Zn) was determined to be 4:1, with a total amount of 3 phr in 100 phr PVC. It was verified that the combination of zinc oleate with uracil derivatives could improve the long-term thermal stability of PVC, and the DAU/Zn was better than that of the OSU/Zn. In addition, through the transmission/haze verification, adding a proper amount of epoxidized soybean oil (ESBO) and phosphite ester to the OSU/Zn system has a certain synergistic effect. The thermal stability and transparency of PVC can be remarkably enhanced.

17.
Environ Sci Pollut Res Int ; 29(35): 53420-53432, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35288852

RESUMO

Due to the semi-closed structure of the tunnel, serious air pollution in tunnels from vehicle exhaust becomes an issue which needed to be addressed. Among the exhaust, nitric oxide (NO) is typically considered as one of the main pollutants. In this paper, a superhydrophobic photocatalytic coating was fabricated by a spraying method by airbrush with a WO3/TiO2 photocatalysis for NO degradation. The water advanced contact angle (WACA) of the coating reached 166.32°, and the WACA was still above 145° after the 30 times abrasion test. The coating exhibited an excellent ability to remove inorganic and organic pollutants. Also, the NO degradation efficiency of this superhydrophobic coating under ultraviolet and visible light sources and humid environments was tested. When the relative humidity reached 98%, the NO degradation efficiency of the coating remained unchanged under visible light irradiation compared with the relative humidity of 45%. In addition, the coating exhibited prominent stability of NO degradation during the cyclic test. Furthermore, the WT coating showed stability and synergy of self-cleaning and photocatalysis toward NO degradation, which ensured the long-term use of the coating. Finally, a synergistic mechanism for self-cleaning and photocatalysis was proposed. This may provide a new idea and support for the application of photocatalytic technology in the degradation of NO in the tunnel.

18.
Plants (Basel) ; 11(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35890444

RESUMO

(1) Background: With the increase in people's consumption of processed oat products, the production of selenium (Se)-enriched oat has become a possibility to supplement the human body with Se. Therefore, the effects of various factors on the Se-enriched ability and yield of different oat varieties were comprehensively studied. (2) Methods: cv."Pinyan 5" and cv."Bayou 18" were applied at the stem-elongation stage and heading stage in the Jinzhong (JZ), and cv."Bayou 1" and cv."Jinyan 18" were applied at the heading stage and flowering stage in the northwestern Shanxi (JXB) with different doses of Na2SeO3 (0, 5.48, 10.96, 21.92, 43.84, 65.76, 98.64, 0, 5.48, 10.96, 21.92, 43.84, 65.76, 98.64, 147.96 g hm-2) by soil application and foliar spraying. (3) Results: The grain Se content and yield of oat were affected by the variety, Se application dose, stage and method of Se supplementation. Additionally, the Se content in oat grain was positively correlated with the Se application dose while the yield of oat first increased and then decreased with the Se application dose. (4) Conclusions: In the JZ and JXB, 21.92 g hm-2 and 43.84 g hm-2 Se was sprayed on the leaves of cv."Bayou 18" and cv."Bayou 1" at the heading stage, respectively, was the most effective Se biofortification program.

19.
Signal Transduct Target Ther ; 7(1): 94, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35322018

RESUMO

To date, the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined 399,600,607 cases and 5,757,562 deaths worldwide. COVID-19 is a serious threat to human health globally. The World Health Organization (WHO) has declared COVID-19 pandemic a major public health emergency. Vaccination is the most effective and economical intervention for controlling the spread of epidemics, and consequently saving lives and protecting the health of the population. Various techniques have been employed in the development of COVID-19 vaccines. Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response. This review summarizes current knowledge on the structural characteristics, antigen design strategies, delivery systems, industrialization potential, quality control, latest clinical trials and real-world data of COVID-19 mRNA vaccines as well as mRNA technology. Current challenges and future directions in the development of preventive mRNA vaccines for major infectious diseases are also discussed.


Assuntos
Vacinas contra COVID-19 , COVID-19 , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Humanos , Pandemias/prevenção & controle , RNA Mensageiro/genética , SARS-CoV-2/genética , Vacinas Sintéticas , Vacinas de mRNA
20.
Cell Stem Cell ; 29(1): 70-85.e6, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34624205

RESUMO

In aging, androgenic alopecia, and genetic hypotrichosis disorders, hair shaft miniaturization is often associated with hair follicle stem cell (HFSC) loss. However, the mechanism causing this stem cell depletion in vivo remains elusive. Here we show that hair shaft loss or a reduction in diameter shrinks the physical niche size, which results in mechanical compression of HFSCs and their apoptotic loss. Mechanistically, cell compression activates the mechanosensitive channel Piezo1, which triggers calcium influx. This confers tumor necrosis factor alpha (TNF-α) sensitivity in a hair-cycle-dependent manner in otherwise resistant HFSCs and induces ectopic apoptosis. Persistent hair shaft miniaturization during aging and genetic hypotrichosis disorders causes long-term HFSC loss by inducing continuous ectopic apoptosis through Piezo1. Our results identify an unconventional role of the inert hair shaft structure as a functional niche component governing HFSC survival and reveal a mechanosensory axis that regulates physical-niche-atrophy-induced stem cell depletion in vivo.


Assuntos
Cálcio , Fator de Necrose Tumoral alfa , Folículo Piloso , Miniaturização , Células-Tronco
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