Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.060
Filtrar
1.
Braz. J. Biol. ; 83: 1-11, 2023. tab, graf, ilus
Artigo em Inglês | VETINDEX, VETINDEX | ID: vti-765503

RESUMO

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.(AU)


O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.(AU)


Assuntos
Animais , Bovinos , Telencéfalo , Neuroglobina/análise , Fator 1 Induzível por Hipóxia/análise , Imuno-Histoquímica , Reação em Cadeia da Polimerase em Tempo Real , Western Blotting
2.
Braz. J. Biol. ; 83: 1-15, 2023. tab, graf, ilus
Artigo em Inglês | VETINDEX, VETINDEX | ID: vti-765481

RESUMO

Background: The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim: The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method: The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results: Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion: This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.(AU)


Contexto: O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo: O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método: O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados: Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão: Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.(AU)


Assuntos
Animais , Adulto Jovem , Adulto , Bovinos , Bovinos , Cérebro/anatomia & histologia , Cérebro/fisiologia , Fenômenos Bioquímicos , Neuroglobina/análise , Fator 1 Induzível por Hipóxia/análise
3.
Braz. j. biol ; 83: e245330, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1339394

RESUMO

Abstract Background The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. Aim The study examined the expression of Neuroglobin (Ngb) and Hypoxia-inducible factor-1α (Hif-1α) in adult and young yak brain tissues, and provided researchers with meaningful insight into the anatomy, physiology, and biochemistry of this mammal. Method The study employed immunohistochemistry (IHC), quantitative real-time PCR (qRT-PCR), and Western blot (WB) to obtain the results. Results Ngb and Hif-1α were significantly (P<0.05) expressed in the cerebellar cortex, piriform lobe, medulla, and corpus callosum of the adult yak while in the young yak brain tissues, the protein expressions were significantly found in the white matter of the cerebellum, pineal gland, corpus callosum, and cerebellar cortex. The Ngb and Hif-1α expression showed similarities and differences. This may have resulted from similar animal species, source of nutrition, age factors, brain size, emotional activities, and communication. The findings documented that Ngb and Hif-1α are commonly expressed in various adult and young yak brain tissues. Multiple roles in the brain tissues of the adult and young yaks are involved in the expression and distribution and are proposed to play a significant role in the adaptation of the yak to the high altitude environment. Conclusion This study provides meaningful data to understand the adaptive mechanism to hypoxia and recommended researchers to expand on the adaptive mechanism and brain tissues that are not recorded.


Resumo Contexto O cérebro é um órgão que funciona como o centro do sistema nervoso em todos os animais vertebrados e na maioria dos invertebrados. Objetivo O estudo examinou a expressão de neuroglobina (Ngb) e fator-1α indutível por hipóxia (Hif-1α) em tecidos cerebrais de iaques adultos e jovens e forneceu aos pesquisadores uma visão significativa da anatomia, fisiologia e bioquímica desse mamífero. Método O estudo utilizou imuno-histoquímica (IHC), PCR quantitativo em tempo real (qRT-PCR) e western blot (WB) para a obtenção dos resultados. Resultados Ngb e Hif-1α foram significativamente (P < 0,05) expressos no córtex cerebelar, lobo piriforme, medula e corpo caloso do iaque adulto, enquanto nos tecidos cerebrais do iaque jovem as expressões proteicas foram encontradas significativamente na substância branca do cerebelo, glândula pineal, corpo caloso e córtex cerebelar. A expressão de Ngb e Hif-1α apresentou semelhanças e diferenças. Isso pode ter resultado de espécies animais semelhantes, fonte de nutrição, fatores de idade, tamanho do cérebro, atividades emocionais e comunicação. Os resultados documentaram que o Ngb e o Hif-1α são comumente expressos em vários tecidos cerebrais de iaques adultos e jovens. Múltiplos papéis nos tecidos cerebrais de iaques adultos e jovens estão envolvidos na expressão e distribuição e são propostos para desempenhar um papel significativo na adaptação do iaque ao ambiente de alta altitude. Conclusão Este estudo fornece dados significativos para compreender o mecanismo adaptativo à hipóxia e recomendou que os pesquisadores expandissem o mecanismo adaptativo e os tecidos cerebrais que não foram registrados.


Assuntos
Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Hipóxia , Encéfalo , RNA Mensageiro , Bovinos , Neuroglobina
4.
Braz. j. biol ; 83: e248911, 2023. tab, graf
Artigo em Inglês | MEDLINE, LILACS, VETINDEX | ID: biblio-1339362

RESUMO

Abstract The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.


Resumo O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.


Assuntos
Animais , Telencéfalo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , RNA Mensageiro/genética , Bovinos , Adaptação Fisiológica , Neuroglobina
5.
Climacteric ; : 1-4, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504301

RESUMO

OBJECTIVE: This article reports the first live birth after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency in China. METHODS: A patient with myelodysplastic syndrome received ovarian tissue cryopreservation before hematopoietic stem cell transplantation, and six ovarian cortex strips were thawed and transplanted into her peritoneal pocket 2 years later. RESULTS: Pregnancy occurred spontaneously 27 months after grafting, and a healthy girl was born at 38 weeks gestation. Until now, the child has developed normally without any major diseases. CONCLUSIONS: We report the first live birth resulting from ovarian tissue cryopreservation and transplantation in China.

6.
Zhonghua Yi Shi Za Zhi ; 52(2): 111-115, 2022 Mar 28.
Artigo em Chinês | MEDLINE | ID: mdl-35570347

RESUMO

Wan's gynecology and obstetrics (Wan Shi Nv Ke), collected by the library of China Academy of Chinese Medical Sciences, was examined with the field method. It was found some issues existed both in the recording and description of Wan's gynecology and obstetrics (Wan Shi Nv Ke) collected by the library of China Academy of Chinese Medical Sciences in the electronic catalogue of ancient books and in the General catalogue of ancient books of traditional Chinese Medicine (Zhong Guo Zhong Yi Gu Ji Zong Mu), in terms of the same version with different registration, wrong publication time, some contents missed in publication, and the version actually not collected.

7.
Cell ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35561684

RESUMO

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

8.
Eur Rev Med Pharmacol Sci ; 26(8): 2918-2925, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35503636

RESUMO

OBJECTIVE: Despite advances in plastic and reconstructive surgery, repairing soft tissue defects of the foot remains a complex surgical challenge when conventional methods cannot cover defects. We presented a case in which a free flap was used for reconstruction and reviewed the literature. PATIENTS AND METHODS: A 75-year-old woman with an acral melanoma history had a large exophytic mass on her right foot. Using PubMed, we found that reconstructive options in the literature include local flaps, fascial flaps, muscle flaps, and free flaps. RESULTS: Melanoma recurred four times at the same site after complete excision of the compound nevi in the present case. Melan A, Vimentin (+), S-100 (+), and HMB-45 positivity were found in immunohistochemical staining and increased Ki-67 proliferation. The defects in soft tissue are repaired using a free anterolateral thigh perforator flap. No complications were raised in the patient. CONCLUSIONS: Foot melanoma is difficult to be resected because it necessitates a wide excision, which can result in large defects. The free flap, in our experience, can easily be performed while preserving function and improving cosmesis. This flap is an appealing option for concealing defects in the distal extremities.


Assuntos
Melanoma , Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Idoso , Doença Crônica , Feminino , Humanos , Melanoma/cirurgia , Retalho Perfurante/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Recidiva , Neoplasias Cutâneas , Transplante de Pele/métodos , Lesões dos Tecidos Moles/cirurgia , Coxa da Perna/cirurgia , Resultado do Tratamento
9.
Artigo em Chinês | MEDLINE | ID: mdl-35545597

RESUMO

Objective: To explore the occupational hazards caused by three kinds of welding operations, and to provide data support for individual protection. Methods: In October 2020, the welding fumes, metal elements and welding arc generated by three welding operations of argon gas shielded welding (JS80 welding wire) , manual welding (ZS60A welding rod) and carbon dioxide shielded welding (907A flux cored wire) were collected and measured in the welding laboratory. The samples were analyze and compare in the laboratory, and the differences of the occupational hazard factors of the three welding operations were judged. Results: The concentration of welding fume produced by carbon dioxide shielded welding, manual welding (ZS60A electrode) , and argon gas shielded welding (JS80 welding wires) were 6.80 mg/m(3), 6.17 mg/m(3), and 3.13 mg/m(3), respectively. The effective irradiance of the welding arc outside the welding mask from high to low is manual welding (ZS60A electrode) , carbon dioxide shielded welding (907A flux-cored welding wire) , and argon shielded welding (JS80 welding wire) , respectively 1 010.7, 740.9, 589.5 µW/cm(2). The long-wave ultraviolet UVA intensity generated by argon shielded welding (JS80 welding wire) is the largest, which is 1 500 µW/cm(2). The content of Mn in the three welding operations is the highest, and JS80 welding wire has the highest Mn content of 128493.2 mg/kg. 907A flux cored wire has the highest Ti content, which is 24355.5mg/kg. The electrode ZS60A has the highest Cu content, which is 24422.12 mg/kg. Conclusion: The intensity of occupational hazards is different in the three kinds of welding operations, so the methods of personal protective equipment, field exposure assessment and health monitoring should be more targeted.


Assuntos
Poluentes Ocupacionais do Ar , Exposição Ocupacional , Soldagem , Poluentes Ocupacionais do Ar/análise , Argônio/análise , Dióxido de Carbono/análise , Gases/análise , Exposição Ocupacional/análise , Soldagem/métodos
10.
Nat Commun ; 13(1): 2559, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562350

RESUMO

c-MYC (MYC) is a major driver of prostate cancer tumorigenesis and progression. Although MYC is overexpressed in both early and metastatic disease and associated with poor survival, its impact on prostate transcriptional reprogramming remains elusive. We demonstrate that MYC overexpression significantly diminishes the androgen receptor (AR) transcriptional program (the set of genes directly targeted by the AR protein) in luminal prostate cells without altering AR expression. Analyses of clinical specimens reveal that concurrent low AR and high MYC transcriptional programs accelerate prostate cancer progression toward a metastatic, castration-resistant disease. Data integration of single-cell transcriptomics together with ChIP-seq uncover an increase in RNA polymerase II (Pol II) promoter-proximal pausing at AR-dependent genes following MYC overexpression without an accompanying deactivation of AR-bound enhancers. Altogether, our findings suggest that MYC overexpression antagonizes the canonical AR transcriptional program and contributes to prostate tumor initiation and progression by disrupting transcriptional pause release at AR-regulated genes.

11.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(5): 423-430, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35527456

RESUMO

Objectives: To evaluate the reliability and validity of the Chinese version of the test of the adherence to inhalers (TAI) in Chinese patients with chronic airway disease. Methods: Based on the English version of TAI, the items of the Chinese version of TAI were determined after forward-backward translation and cultural adaption. Totally, 165 patients with chronic obstructive pulmonary disease (COPD) and asthma were enrolled from Respiratory Clinic of the Second Xiangya Hospital of Central South University from July to November 2021, and a questionnaire survey was conducted using the Chinese version of TAI and the Morisky medication adherence scale 8-item version (MMAS-8). The content validity of the scale was expressed by content validity index (CVI) and the construct validity was analyzed by exploratory factor analysis (EFA). The convergence validity was evaluated by Pearson correlation analysis. The reliability of the scale was expressed by Cronbach's α coefficient, the split-half reliability and test-retest reliability. Results: The CVI was 0.966. There were 10 items in total. Two factors were extracted from the Chinese version of TAI and the cumulative variance contribution rate was 57.236%. The load value of each item was more than 0.400 and the factor attribution of the item was consistent with the original scale. The total score of the Chinese version of TAI was positively correlated with the total score of the MMAS-8(r=0.835,P<0.001). The Cronbach's α of the overall scale was 0.843, the Guttman's half-reliability coefficient was 0.796 and the test-retest reliability was 0.884 (P<0.001), respectively. Conclusions: The Chinese version of TAI has good reliability and validity, which may be a reliable tool for evaluating the adherence to inhalers of patients with chronic airway disease in China.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Asma/tratamento farmacológico , China , Humanos , Nebulizadores e Vaporizadores , Psicometria , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Reprodutibilidade dos Testes , Inquéritos e Questionários
12.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(5): 510-514, 2022 May 12.
Artigo em Chinês | MEDLINE | ID: mdl-35527467

RESUMO

Coronavirus disease (COVID-19) and tuberculosis (TB) are two respiratory infectious diseases with a high incidence of transmission, mainly via respiratory droplets and both can weaken the immune system and lower the number of CD4+T cells in patients. COVID-19 can occur before, at the same time or after the diagnosis of TB. Patients with pulmonary TB are more likely to have co-infection when they have a history of epidemiological exposure to COVID-19. At present, many cases of nosocomial infection of COVID-19 caused by ineffective prevention and control measures in tuberculosis hospitals have been reported successively at domestic and overseas. Therefore, it is urgent to strengthen the prevention and control of nosocomial infections in tuberculosis hospitals. The superposition of the two diseases can lead to a worsening prognosis, aggravating the patient's condition and making treatment more difficult. In addition, in the context of the new coronavirus epidemic, early recognition of co-infection with new coronavirus should be made when TB patients in chest hospitals present with symptoms such as aggregated fever or progressive disease. At the same time, we should focus on identifying the clinical and imaging manifestations of TB and COVID-19 co-infection. At present, research on COVID-19 complicated with pulmonary TB is scarce, and there are disputes on many aspects. As a country with a high prevalence of tuberculosis, it is of great practical significance to identify the clinical characteristics, outcomes, and treatment of the two infectious diseases in China.


Assuntos
COVID-19 , Coinfecção , Infecção Hospitalar , Tuberculose Pulmonar , Tuberculose , Coinfecção/epidemiologia , Humanos , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/epidemiologia
13.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(4): 554-560, 2022 Apr 20.
Artigo em Chinês | MEDLINE | ID: mdl-35527491

RESUMO

OBJECTIVE: To construct a HEK293 cell line stably overexpressing TrxR1 as a cell model for functional study of TrxR1 and screening of TrxR1-targeting drugs. METHODS: TrxR1 gene was amplified by PCR and ligated with the lentivirus expression vector pLVX-Puro, which was transformed into Escherichia coli and identified by Sanger dideoxy sequencing. HEK293 cells were infected with the recombinant lentivirus vector (pLVX-Puro-TXNRD1) and screened with Puromycin for cell clones with stable TrxR1 overexpression (HEK293-TrxR1-OE cells). HEK293-TrxR1-OE cells, along with HEK293 cells infected with pLVX-Puro vector (HEK293-NC) and normal HEK293 cells, were tested for mRNA and protein expression levels of TrxR1 using RT-qPCR and Western blotting. TrxR1 enzyme activity in the cells was evaluated with insulin endpoint assay and TRFS-green probe imaging. The sensitivity of the cells to auranofin, a specific TrxR1 inhibitor, was determined with CCK8 assay. RESULTS: TrxR1 gene was successfully inserted into the lentiviral vector pLVX-Puro as confirmed by DNA sequencing. The enzyme activity and mRNA and protein expression levels of TrxR1 were significantly higher in HEK293-TrxR1-OE cells than in HEK293 and HEK293-NC cells (P < 0.005). The inhibitory effects of auranofin on proliferation and cellular TrxR1 enzyme activity were significantly attenuated in HEK293-TrxR1-OE cells as compared with HEK293 and HEK293-NC cells (P < 0.005). CONCLUSION: We successfully obtained a HEK293 cell line with stable TrxR1 overexpression, which shows resistance to auranofin and can be used for screening TrxR1 targeting drugs.


Assuntos
Auranofina , Lentivirus , Linhagem Celular Tumoral , Vetores Genéticos , Células HEK293 , Humanos , Lentivirus/genética , RNA Mensageiro , Transfecção
14.
Nat Cancer ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534777

RESUMO

Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation. Furthermore, IKAROS displays an unexpected functional cooperativity and extensive chromatin co-occupancy with mixed lineage leukemia (MLL)1-MENIN and the regulator MEIS1 and an extensive hematopoietic transcriptional complex involving homeobox (HOX)A10, MEIS1 and IKAROS. This dependency could be therapeutically exploited by inducing IKAROS protein degradation with immunomodulatory imide drugs (IMiDs). Finally, we demonstrate that combined IKAROS degradation and MENIN inhibition effectively disrupts leukemogenic transcriptional networks, resulting in synergistic killing of leukemia cells and providing a paradigm for improved drug targeting of transcription and an opportunity for rapid clinical translation.

16.
Cancer Immunol Res ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35605261

RESUMO

We applied our computational algorithm TRUST4 to assemble immune receptor (TCR/BCR) repertoires from approximately twelve thousand RNA-seq samples from The Cancer Genome Atlas (TCGA) and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 (CDR3) sequences, we observed that the expression of CCL5 and MZB1 are the most positively correlated genes with T-cell clonal expansion and B-cell clonal expansion, respectively. We analyzed amino acid evolution during B-cell receptor somatic hypermutation and identified tyrosine as the preferred residue. We found that IgG1+IgG3 antibodies together with FcRn were associated with complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity or phagocytosis. In addition to B-cell infiltration, we discovered that B-cell clonal expansion and IgG1+IgG3 antibodies are also correlated with better patient outcomes. Finally, we created a website, VisualizIRR, for users to interactively explore and visualize the immune repertoires in this study.

17.
Zhonghua Shao Shang Za Zhi ; 38(5): 422-433, 2022 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-35599418

RESUMO

Objective: To investigate the effects of non-muscle myosin Ⅱ (NMⅡ) gene silenced bone marrow-derived mesenchymal stem cells (BMMSCs) on pulmonary extracellular matrix (ECM) and fibrosis in rats with acute lung injury (ALI) induced by endotoxin/lipopolysaccharide (LPS). Methods: The experimental research methods were adopted. Cells from femur and tibial bone marrow cavity of four one-week-old male Sprague-Dawley rats were identified as BMMSCs by flow cytometry, and the third passage of BMMSCs were used in the following experiments. The cells were divided into NMⅡ silenced group transfected with pHBLV-U6-ZsGreen-Puro plasmid containing small interference RNA sequence of NMⅡ gene, vector group transfected with empty plasmid, and blank control group without any treatment, and the protein expression of NMⅡ at 72 h after intervention was detected by Western blotting (n=3). The morphology of cells was observed by an inverted phase contrast microscope and cells labeled with chloromethylbenzoine (CM-DiⅠ) in vitro were observed by an inverted fluorescence microscope. Twenty 4-week-old male Sprague-Dawley rats were divided into blank control group, ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group according to the random number table, with 5 rats in each group. Rats in blank control group were not treated, and rats in the other 3 groups were given LPS to induce ALI. Immediately after modeling, rats in ALI alone group were injected with 1 mL normal saline via tail vein, rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were injected with 1×107/mL BMMSCs and NMⅡ gene silenced BMMSCs of 1 mL labelled with CM-DiⅠ via tail vein, and rats in blank control group were injected with 1 mL normal saline via tail vein at the same time point, respectively. At 24 h after intervention, the lung tissue was collected to observe intrapulmonary homing of the BMMSCs by an inverted fluorescence microscope. Lung tissue was collected at 24 h, in 1 week, and in 2 weeks after intervention to observe pulmonary inflammation by hematoxylin eosin staining and to observe pulmonary fibrosis by Masson staining, and the pulmonary fibrosis in 2 weeks after intervention was scored by modified Ashcroft score (n=5). The content of α-smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), and MMP-9 was detected by immunohistochemistry in 2 weeks after intervention (n=3), the activity of superoxide dismutase (SOD), malondialdehyde, myeloperoxidase (MPO) was detected by enzyme-linked immunosorbent assay at 24 h after intervention (n=3), and the protein expressions of CD11b and epidermal growth factor like module containing mucin like hormone receptor 1 (EMR1) in 1 week after intervention were detected by immunofluorescence staining (n=3). Data were statistically analyzed with one-way analysis of variance, Bonferroni method, and Kruskal-Wallis H test. Results: At 72 h after intervention, the NMⅡprotein expression of cells in NMⅡ silenced group was significantly lower than those in blank control group and vector group (with P values <0.01). BMMSCs were in long spindle shape and grew in cluster shaped like vortexes, which were labelled with CM-DiⅠ successfully in vitro. At 24 h after intervention, cell homing in lung of rats in ALI+NMⅡ silenced BMMSC group was more pronounced than that in ALI+BMMSC group, while no CM-DiⅠ-labelled BMMSCs were observed in lung of rats in blank control group and ALI alone group. There was no obvious inflammatory cell infiltration in lung tissue of rats in blank control group at all time points, while inflammatory cell infiltration in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly less than that in ALI alone group at 24 h after intervention, and alveolar wall turned to be thinner and a small amount of congestion in local lung tissue appeared in rats of the two groups in 1 week and 2 weeks after intervention. In 1 week and 2 weeks after intervention, collagen fiber deposition in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group was significantly aggravated compared with that in blank control group, while collagen fiber deposition in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly improved compared with that in ALI alone group. In 2 weeks after intervention, modified Ashcroft scores for pulmonary fibrosis of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were 2.36±0.22, 1.62±0.16, 1.06±0.26, respectively, significantly higher than 0.30±0.21 in blank control group (P<0.01). Modified Ashcroft scores for pulmonary fibrosis of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly lower than that in ALI alone group (P<0.01), and modified Ashcroft score for pulmonary fibrosis of rats in ALI+NMⅡ silenced BMMSC group was significantly lower than that in ALI+BMMSC group (P<0.01). In 2 weeks after intervention, the content of α-SMA in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly decreased compared with that in ALI alone group (P<0.05 or P<0.01). The content of MMP-2 in lung tissue of rats in the 4 groups was similar (P>0.05). The content of MMP-9 in lung tissue of rats in ALI alone group was significantly increased compared with that in blank control group (P<0.01), and the content of MMP-9 in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01). At 24 h after intervention, the activity of malondialdehyde, SOD, and MPO in lung tissue of rats in ALI alone group, ALI+BMMSC group, and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in blank control group (P<0.01), the activity of malondialdehyde in lung tissue of rats in ALI+NMⅡ silenced BMMSC group and the activity of SOD in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group were significantly increased compared with that in ALI alone group (P<0.05 or P<0.01), and the activity of SOD in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). The activity of MPO in lung tissue of rats in ALI+BMMSC group and ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI alone group (P<0.01), and the activity of MPO in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly decreased compared with that in ALI+BMMSC group (P<0.01). In 1 week after intervention, the protein expression of CD11b in lung tissue of rats in ALI+NMⅡ silenced BMMSC group was significantly increased compared with those in the other three groups (P<0.05 or P<0.01), while the protein expressions of EMR1 in lung tissue of rats in the four groups were similar (P>0.05). Conclusions: Transplantation of NMⅡ gene silenced BMMSCs can significantly improve the activity of ECM components in the lung tissue in LPS-induced ALI rats, remodel its integrity, and enhance its antioxidant capacity, and alleviate lung injury and pulmonary fibrosis.


Assuntos
Lesão Pulmonar Aguda , Células-Tronco Mesenquimais , Fibrose Pulmonar , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/terapia , Animais , Medula Óssea , Colágeno/metabolismo , Endotoxinas , Matriz Extracelular , Lipopolissacarídeos/efeitos adversos , Pulmão , Masculino , Malondialdeído/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , Miosina Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Solução Salina/metabolismo , Superóxido Dismutase/metabolismo
18.
Zhonghua Yan Ke Za Zhi ; 58(4): 259-264, 2022 Apr 11.
Artigo em Chinês | MEDLINE | ID: mdl-35391512

RESUMO

Objective: To analyze the influencing factors and the effect of myopia control in children treated with orthokeratology. Methods: It was a retrospective case series study. Data of 137 children from June 2016 to July 2020 in the Optometry Hospital of Wenzhou Medical University who were fitted with orthokeratology lenses and kept wearing them for 24 months were retrospectively reviewed. These children were divided into the modeling group (n=91) and verification group (n=46). The baseline conditions were recorded before they wore the orthokeratology lenses, including age, spherical equivalent refractive power (SER) and pupil area. The decentration distance was measured with a tangential difference map. Axial length (AL) changes of all children during 24 months were calculated. The influencing factors and the effect of myopia control were analyzed, and a regression equation was formulated with the modeling group. Then the influencing factors were imported with the verification group to compare the AL change differences between prediction and measurement. Results: There was statistical difference in AL between baseline and after wearing orthokeratology lenses for 24 months both in the modeling group [(25.16±0.90) mm vs. (25.56±0.82) mm; t=-10.119, P<0.001] and verification group [(25.29±0.71) mm vs. (25.67±0.69) mm; t=-8.785, P<0.001]. The AL changes in the modeling group showed significant correlations with baseline age (r=-0.365, P<0.001), baseline SER (r=0.308, P=0.003), pupil area (r=-0.260, P=0.013) and decentration distance (r=-0.352, P=0.001). The regression equation was as follows: y=1.609-0.056a-0.315b-0.009c+0.054d (y: AL changes, a: baseline age, b: decentration distance, c: pupil area, d: baseline SER). There was no statistical difference between prediction and measurement [(0.40±0.20) mm vs. (0.40±0.32) mm; t=-0.036, P=0.971]. Conclusion: Baseline age, decentration distance, baseline SER and pupil area contributed to predict the effect of myopia control after orthokeratology treatment.


Assuntos
Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Comprimento Axial do Olho , Criança , Topografia da Córnea , Humanos , Miopia/terapia , Refração Ocular , Estudos Retrospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-35430123

RESUMO

Dental implant restoration is a predictable treatment option for replacing missing or damaged teeth. Conventional loading requires a prolonged treatment period and second surgical interventions. The aim of this study was to compare the clinical outcomes between immediate and non-immediate (early or conventional) loading in single-implant restorations. A literature search of the PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases was performed in January 2020. Only randomized clinical trials (RCTs) were included. The overall risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs) were used in the analyses. A total of 10 RCTs reporting on 423 patients were included. There was no significant difference in any of the outcomes of interest between the immediate and non-immediate loading cases: implant failure at the patient level (RR 1.29, 95% CI 0.35 to 4.78, P = 0.71), implant failure at the implant level (RR 1.19, 95% CI 0.40 to 3.51, P = 0.75), marginal bone loss (MD -0.04, 95% CI -0.16 to 0.08, P = 0.54). Subgroup analyses showed similar results. Immediate loading had predictable long-term clinical outcomes if the indicated patients were carefully selected. The influences of several technical factors need to be confirmed in additional clinical trials.

20.
Zhonghua Xin Xue Guan Bing Za Zhi ; 50(4): 386-394, 2022 Apr 24.
Artigo em Chinês | MEDLINE | ID: mdl-35399035

RESUMO

Objective: To summarize the clinical characteristics of patients with Takotsubo syndrome (TTS) from China and compare these features with patients from Europe/North America. Methods: We reviewed case reports published between 1990 and 2020 with the key words of "Takotsubo syndrome" "stress cardiomyopathy" "apical balloon syndrome" and "broken heart syndrome", in Wanfang, CNKI, Pubmed and Web of Science databases, and 1 294 articles were identified, including 128 articles reporting 163 cases in China and 1 166 articles reporting 1 256 cases in Europe/North America. The characteristics of demographics, triggers, symptoms, electrocardiogram, echocardiography, left ventriculogram,coronary angiography, treatment and prognosis were analyzed and compared between Chinese and European/North American cases. Results: A total of 1 294 articles (1 419 cases: 163 from China, 1 256 from Europe/North America) were included in the final analysis. The characteristics of Chinese cases included: (1) demographic:the age was (59.6±16.9) years, which was similar with that of European/North American ((59.7±17.4) years, P=0.90), and female accounting for 78.5% (128/163), which was lower than that of European/North American (85.4% (1 073/1 256), P=0.02). (2) Triggers:mental triggers accounted for 48.5% (79/163), physical triggers accounted for 43.6% (71/163), and no triggers accounted for 7.9% (13/163), respectively. Compared with Europe/North America, the ratio of patients with mental triggers was higher in China, while the ratio of patients with physical triggers and no triggers was lower (P<0.05). (3) Symptoms: chest pain (52.8% (86/163)), chest tightness (35.0% (57/163)), shortness of breath (33.1% (54/163)), dizziness (16.0% (26/163)), sweating (15.3% (25/163)), palpitations (12.3% (20/163)), syncope (9.2% (15/163)) abdominal pain/diarrhea (8.6% (14/163)), hypotension (7.4% (12/163)), and fatigue (1.2% (2/163)) were illustrated in sequence. Compared with patients in Europe/North America, the ratio of patients with chest tightness, dizziness, sweating, palpitations, abdominal pain/diarrhea was higher in Chinese patients, while the ratio of patients with hypotension was lower in Chinese patients (P<0.05). (4) Electrocardiogram: main manifestations were myocardial ischemia symptoms, such as ST-segment elevation (63.8% (104/163)), T wave inversion (46.0% (75/163)), ST-segment depression (8.6% (14/163)). Compared with European/North American, the ratio of patients with ST-segment elevation, T wave inversion, and atrioventricular block was higher in Chinese patients (P<0.05). (5) Echocardiography and imaging:apical dyskinesia (59.5% (97/163)) and apical/left ventricular bulbar dilation (36.2%(59/163)) dominated the echocardiography findings. Compared with European/North American, the ratio of patients with apical dyskinesia, apical/left ventricular bulbar dilation, and mitral regurgitation was higher in Chinese patients, while the ratio of patients with dyskinesia in other parts and left ventricular ejection fraction<50% was lower in Chinese patients (P<0.05). Left ventricular angiography showed 36.2% (59/163) of apical dyskinesia in Chinese patients, which was higher than that reported in European/North American patients, and 38.7% (63/163) of apical/left ventricular bulbar dilation was reported in Chinese patients, which was similar to that reported in European/North American patients. Coronary angiography showed percent of no stenosis or stenosis less than 50% was 87.1% (142/163), which was similar to that reported in European/North American patients (P>0.05). The typical type of TTS accounted for 96.3% (157/163), which was significantly higher than that reported in European/ American patients, while the ratio of basal type and midventricular type was lower (P<0.01). (6) Treatment and prognosis:the applied drugs in China were listed in order as following, ß-blockers (41.1% (67/163)), antiplatelet agents (37.4%(61/163)), ACEI/ARB (36.2%(59/163)), anticoagulants (27.0%(44/163)), diuretics (19.6% (32/163)), etc. Compared with Europe/North America, the ratio of antiplatelet agents, anticoagulants, statins, diuretics, and nitrates use was higher in China (P<0.05), while the use of oxygen therapy and IABP was similar (P>0.05). The hospital mortality in China was 5.5% (9/163), during 1-year follow-up the recurrence rate was 3.7% (6/163) and the mortality was 0. The prognosis was similar with that in Europe/North America. Conclusions: Compared with TTS cases in Europe/North America, TTS cases in China also occur usually in middle-aged and elderly women, most of whom have mental/physical triggers and typical imaging manifestations, followed by a low hospital mortality rate and recurrence rate.


Assuntos
Discinesias , Hipotensão , Cardiomiopatia de Takotsubo , Dor Abdominal/complicações , Adulto , Idoso , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Anticoagulantes , Arritmias Cardíacas/complicações , China/epidemiologia , Diuréticos , Tontura/complicações , Discinesias/complicações , Eletrocardiografia , Europa (Continente)/epidemiologia , Feminino , Humanos , Hipotensão/complicações , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária , Volume Sistólico , Cardiomiopatia de Takotsubo/epidemiologia , Cardiomiopatia de Takotsubo/etiologia , Função Ventricular Esquerda
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA