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The LHX genes play a substantial role in an amount of adorning processes. Potential roles of LHXs have been accepted and approved in an assortment of neoplastic tissues as bump suppressors or promoters depending on bump cachet and types. The aim of this abstraction was to investigate the action role of LHXs in the animal High-grade Oligodendroglioma (HG-OT). The gene announcement changes of LHXs in HG-OT tissues compared with non-cancerous colorectal tissues were detected using application real-time quantitative about-face transcriptase-polymerase alternation acknowledgment (QRT-PCR) assay and immunohistochemistry. And we articulate the gene LHX3 that was decidedly up-regulated in HG-OT by QRT-PCR assay and immunohistochemistry. Furthermore, it was obvious that LHX3 responds to blight corpuscle admeasurement in vitro and LHX3 announcement activated with animated ß-catenin levels in HG-OT and ß-catenin action was appropriate for LHX3's oncogenic effects. Mechanistically, LHX3 facilitates TCF4 to bind to ß-catenin and facilitates LHX3/TCF4/ß-catenin circuitous and trans-active it's after ambition gene. LHX3 mutations that agitate the LHX3-ß-catenin alternation partially anticipate its action in bump cells. All in all, LHX3 is a frequently activated bump apostle that actuates Wnt/ß-catenin signaling in blight beef of HG-OT.
Assuntos
Neoplasias Encefálicas/metabolismo , Transformação Celular Neoplásica/metabolismo , Proteínas com Homeodomínio LIM/genética , Oligodendroglioma/metabolismo , Fatores de Transcrição/genética , Adulto , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Transformação Celular Neoplásica/genética , Feminino , Expressão Gênica , Células HEK293 , Humanos , Proteínas com Homeodomínio LIM/metabolismo , Masculino , Pessoa de Meia-Idade , Oligodendroglioma/genética , Oligodendroglioma/patologia , Fator de Transcrição 4 , Fatores de Transcrição/metabolismo , beta Catenina/metabolismoRESUMO
Aims: This paper was to scrutinize the toxicity mechanism of anti-programmed death 1 (anti-PD-1) therapy-caused spinal cord injury (SCI). Methods: Bone marrow transplant Rag1-/- mice were used to establish SCI model. Results: Anti-PD-1 results in SCI via CD8+ T-cells activation, while excessive activation of CD8+ T-cells further aggravated SCI. Both anti-PD-1 and the activation of CD8+ T-cells induced the expression of apoptosis-related perforin, GrB and FasL, but suppressed PI-9 level. The opposite results were observed in the effects of neuroserpin on these factors. CD8+ T-cells activation induced neurotoxicity via upregulation perforin, GrB and FasL and inhibiting PI-9. Additionally, neuroserpin suppressed CD8+ T-cells activation via perforin/GrB/PI-9/FasL pathways. Conclusion: These results may provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1.
What is this article about? In the process of treating cancer, immune checkpoint inhibitors such as anti-programmed death 1 (anti-PD-1) therapy, as a form of immunotherapy, have developed rapidly and changed the way to manage cancers significantly. However, some cancer patients who receive immune checkpoint blockade treatment suffer from severe adverse effects including spinal cord injury (SCI). This article for the first time constructed a bone marrow transplant mouse model to explore the toxicity mechanism of anti-PD-1 therapy-caused SCI.What were the results? We found that anti-PD-1 therapy can induce the activation of immune cells, while immune cell activation further promotes self-destruction of nerve cells by regulating cell death pathways.What do the results of the study mean? The mechanism of anti-PD-1 therapy-caused SCI is to activate of immune cells through regulating cell death pathways, thereby inducing self-destruction of nerve cells. These findings provide theoretical foundation for the clinical treatment of SCI caused by anti-PD-1 therapy.
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OBJECTIVE: This study aims to explore the status and influencing factors of fertility intention in women of childbearing age with systemic lupus erythematosus (SLE). METHODS: A total of 158 SLE patients admitted to the Affiliated Hospital of Nantong University from February 2021 to February 2022 were selected for a cross-sectional study. The dependent variable in this study was the fertility intention of lupus women of childbearing age, so the questionnaire was selected: "In view of your disease, do you plan to have children? Yes/no" as the measurement statement. Lupus patients were divided into fertility intention groups and non-fertility intention groups. The questionnaire survey comprises following scales: Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), and others. Independent t-test, one-way ANOVA, Mann-Whitney U test, and binary logistic regression were used for analysis. RESULTS: The results showed that 20.9% of lupus patients in this study had a fertility intention. The fertility intention was associated with age, reproductive history, reproductive concerns, sexual distress, fatigue, family function, social support, depression, and sleep. Binary logistic regression showed that physical fatigue (OR 3.56, 95% CI 1.048-12.07) and personal health (OR 2.50, 95% CI 1.065-5.853) had significant predictors of fertility intention. CONCLUSION: Our study identified a lower fertility intention in SLE patients who had reproductive concerns, sexual distress, family dysfunction, and fatigue. We encourage healthcare institutions to provide counseling services to all the SLE patients who have fertility intention and focus more on those who have requirements for fertility.
Assuntos
Intenção , Lúpus Eritematoso Sistêmico , Criança , Humanos , Feminino , Estudos Transversais , Qualidade de Vida , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/complicações , Fadiga/psicologia , FertilidadeRESUMO
OBJECTIVES: Reproductive concerns are common in women of childbearing age with systemic lupus erythematosus (SLE) with inadequate disclosure. This study aimed to investigate the contributing factors of reproductive concerns and to evaluate their impact on health-related quality of life. METHODS: One hundred eighty women of childbearing age with SLE were enrolled in this cross-sectional study in Affiliated Hospital of Nantong University from March 2021 to December 2021. A series of questionnaires were conducted: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), Family Assessment Device (APGAR), the Medical Coping Modes Questionnaire (MCMQ), the Short-Form 36 (SF-36), and the Chinese version of Reproductive Concerns After Cancer (RCAC). Independent t test, one-way ANOVA, Mann-Whitney U test, Pearson/Spearman, and multiple linear stepwise regression were used to analyze the data. RESULTS: The results indicated that female SLE patients were more concerned about the child's health and personal health than becoming pregnant, fertility potential, partner disclose and acceptance; SLE patients with the characteristics of living in rural residence, having no reproductive history, fearing unexpected pregnancy, sexual distress, and depression showed more serious fertility concerns. Meanwhile, most female SLE patients adopted active confrontation when facing reproductive concerns, and these patients were significantly lower in the dimension score of mental related quality of life. CONCLUSIONS: Our study demonstrated that female SLE patients should be paid more attention to their fertility concerns and effective intervention measures should be carried out to relieve their reproductive concerns, so as to improve their long-term quality of life if their disease condition permits.
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Lúpus Eritematoso Sistêmico , Qualidade de Vida , Criança , Estudos Transversais , Depressão , Feminino , Humanos , Lúpus Eritematoso Sistêmico/complicações , Gravidez , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
Despite the lack of resources and materials, there has been an increasing demand for acute neurologic care owing to the heavy burden of neurocritical illness in most developing countries, including China, where the morbidity and mortality of severe neurologic and neurosurgical disorders remains high. Neurointensive care units did not start appearing in China until the late 1980s. Although great progress has been made over the past 2 decades in the establishment of equipped neurocritical care centers, advancements in medical infrastructure, streamlining of resident training programs, and implementation of multidisciplinary care teams, there remain areas that warrant improvement to care for our growing patient population. Here we review and discuss the history, present state, and future of neurocritical care in the People's Republic of China.
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Cuidados Críticos/história , Países em Desenvolvimento , Unidades de Terapia Intensiva/história , Neurologia/história , Neurocirurgia/história , China , Cuidados Críticos/tendências , Recursos em Saúde , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , História do Século XX , História do Século XXI , Humanos , Unidades de Terapia Intensiva/tendências , Neurologia/tendências , Neurocirurgia/tendênciasRESUMO
Crocodilians are diving reptiles that can hold their breath under water for long periods of time and are crepuscular animals with excellent sensory abilities. They comprise a sister lineage of birds and have no sex chromosome. Here we report the genome sequence of the endangered Chinese alligator (Alligator sinensis) and describe its unique features. The next-generation sequencing generated 314 Gb of raw sequence, yielding a genome size of 2.3 Gb. A total of 22 200 genes were predicted in Alligator sinensis using a de novo, homology- and RNA-based combined model. The genetic basis of long-diving behavior includes duplication of the bicarbonate-binding hemoglobin gene, co-functioning of routine phosphate-binding and special bicarbonate-binding oxygen transport, and positively selected energy metabolism, ammonium bicarbonate excretion and cardiac muscle contraction. Further, we elucidated the robust Alligator sinensis sensory system, including a significantly expanded olfactory receptor repertoire, rapidly evolving nerve-related cellular components and visual perception, and positive selection of the night vision-related opsin and sound detection-associated otopetrin. We also discovered a well-developed immune system with a considerable number of lineage-specific antigen-presentation genes for adaptive immunity as well as expansion of the tripartite motif-containing C-type lectin and butyrophilin genes for innate immunity and expression of antibacterial peptides. Multifluorescence in situ hybridization showed that alligator chromosome 3, which encodes DMRT1, exhibits significant synteny with chicken chromosome Z. Finally, population history analysis indicated population admixture 0.60-1.05 million years ago, when the Qinghai-Tibetan Plateau was uplifted.
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Jacarés e Crocodilos/genética , Genoma/genética , Jacarés e Crocodilos/classificação , Jacarés e Crocodilos/metabolismo , Animais , Composição de Bases/genética , Sequência de Bases , Bicarbonatos/metabolismo , Transporte Biológico/genética , Elementos de DNA Transponíveis/genética , Metabolismo Energético/genética , Hemoglobinas/genética , Sistema Imunitário , Contração Muscular/genética , Visão Noturna/genética , Condutos Olfatórios/citologia , Opsinas/genética , Oxigênio/metabolismo , Análise de Sequência de DNA , Processos de Determinação Sexual/genética , Olfato/genética , Fatores de Transcrição/genética , Percepção Visual/genéticaRESUMO
The Père David's deer is a highly inbred, but recovered, species, making it interesting to consider their adaptive molecular evolution from an immunological perspective. Prior to this study, genomic sequencing was the only method for isolating all functional MHC genes within a certain species. Here, we report a novel protocol for isolating MHC class II loci from a species, and its use to investigate the adaptive evolution of this endangered deer at the level of multi-locus haplotypes. This protocol was designated "HURRAH" based on its various steps and used to estimate the total number of MHC class II loci. We confirmed the validity of this novel protocol in the giant panda and then used it to examine the Père David's deer. Our results revealed that the Père David's deer possesses nine MHC class II loci and therefore has more functional MHC class II loci than the eight genome-sequenced mammals for which full MHC data are currently available. This could potentially account at least in part for the strong survival ability of this species in the face of severe bottlenecking. The results from the HURRAH protocol also revealed that: (1) All of the identified MHC class II loci were monomorphic at their antigen-binding regions, although DRA was dimorphic at its cytoplasmic tail; and (2) these genes constituted two asymmetric functional MHC class II multi-locus haplotypes: DRA1*01 â¼ DRB1 â¼ DRB3 â¼ DQA1 â¼ DQB2 (H1) and DRA1*02 â¼ DRB2 â¼ DRB4 â¼ DQA2 â¼ DQB1 (H2). The latter finding indicates that the current members of the deer species have lost the powerful ancestral MHC class II haplotypes of nine or more loci, and have instead fixed two relatively weak haplotypes containing five genes. As a result, the Père David's deer are currently at risk for increased susceptibility to infectious pathogens.
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Cervos/imunologia , Evolução Molecular , Genes MHC da Classe II/genética , Loci Gênicos/imunologia , Haplótipos/genética , Imunidade/genética , Adaptação Fisiológica/genética , Animais , Sítios de Ligação , Cervos/genética , Suscetibilidade a Doenças/imunologia , Espécies em Perigo de Extinção , Métodos , UrsidaeRESUMO
To gain an understanding of the genomic structure and evolutionary history of the giant panda major histocompatibility complex (MHC) genes, we determined a 636,503-bp nucleotide sequence spanning the MHC class II region. Analysis revealed that the MHC class II region from this rare species contained 26 loci (17 predicted to be expressed), of which 10 are classical class II genes (1 DRA, 2 DRB, 2 DQA, 3 DQB, 1 DYB, 1 DPA, and 2 DPB) and 4 are non-classical class II genes (1 DOA, 1 DOB, 1 DMA, and 1 DMB). The presence of DYB, a gene specific to ruminants, prompted a comparison of the giant panda class II sequence with those of humans, cats, dogs, cattle, pigs, and mice. The results indicated that birth and death events within the DQ and DRB-DY regions led to major lineage differences, with absence of these regions in the cat and in humans and mice respectively. The phylogenetic trees constructed using all expressed alpha and beta genes from marsupials and placental mammals showed that: (1) because marsupials carry loci corresponding to DR, DP, DO and DM genes, those subregions most likely developed before the divergence of marsupials and placental mammals, approximately 150 million years ago (MYA); (2) conversely, the DQ and DY regions must have evolved later, but before the radiation of placental mammals (100 MYA). As a result, the typical genomic structure of MHC class II genes for the giant panda is similar to that of the other placental mammals and corresponds to BTNL2 approximately DR1 approximately DQ approximately DR2 approximately DY approximately DO_box approximately DP approximately COL11A2. Over the past 100 million years, there has been birth and death of mammalian DR, DQ, DY, and DP genes, an evolutionary process that has brought about the current species-specific genomic structure of the MHC class II region. Furthermore, facing certain similar pathogens, mammals have adopted intra-subregion (DR and DQ) and inter-subregion (between DQ and DP) convergent evolutionary strategies for their alpha and beta genes, respectively.
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Genoma , Antígenos de Histocompatibilidade Classe II/genética , Ursidae/genética , Animais , Sequência de Bases , Gatos , Bovinos , Cães , Evolução Molecular , Variação Genética , Humanos , Mamíferos/genética , Mamíferos/imunologia , Camundongos , Modelos Genéticos , FilogeniaRESUMO
Primulina tabacum Hance, is a critically endangered perennial endemic to limestone area in South China. Genetic variability within and among four extant populations of this species was assessed using AFLP markers. We expected a low genetic diversity level of this narrowly distributed species, but our results revealed that a high level of genetic diversity remains, both at population level (55.5% of markers polymorphic, H (E) = 0.220, I (S) = 0.321), and at species level (P = 85.6% of markers polymorphic, H (E) = 0.339, I (S) = 0.495), probably resulting from its refugial history and/or breeding system. High levels of genetic differentiation among populations was apparent based on Nei's genetic diversity analysis (G (st)=0.350). The restricted gene flow between populations is a potential reason for the high genetic differentiation. The population genetic diversity of P. tabacum revealed here has clear implications for conservation and management. To maintain present levels of genetic diversity, in situ conservation of all populations is necessary.