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1.
Med Sci Monit ; 27: e932318, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34663780

RESUMO

BACKGROUND The partial pressure of arterial oxygen (PaO2) is critical to the outcome of patients with traumatic brain injury (TBI). However, it is not clear what range of PaO2 should be maintained to improve patient outcome. The aim of this study was to explore the PaO2 value needed in the acute phase of TBI and provide new evidence for clinical practice. MATERIAL AND METHODS A total of 153 patients with TBI were enrolled retrospectively. Univariate and multivariate logistic regression analyses were conducted on sex, Glasgow Coma Scale (GCS) score on admission, PaO2 within 6 h of admission, oxygenation index, and other factors. The Glasgow Outcome Score (GOS) of the patient at discharge was used as an indicator of outcome. The good outcome group had GOS ≥4, and the poor outcome group had GOS <4. RESULTS The 153 patients were divided into a good outcome group (n=62) and poor outcome group (n=91). There was a significant difference in sex, admission GCS, surgery, airway status, PaO2, and oxygen index within 6 h of admission between the 2 groups. Logistic regression analysis showed that PaO2 <60 mmHg, male sex, and admission GCS score of 3 to 12 were independent risk factors for a poor outcome. CONCLUSIONS Patients with TBI having PaO2 <60 mmHg within 6 h after admission were more likely to have poor outcomes. The upper limit value of PaO2 that affects the outcome of TBI in patients has not been found.

2.
Elife ; 102021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569930

RESUMO

Transient receptor potential melastatin 7 (TRPM7) contributes to a variety of physiological and pathological processes in many tissues and cells. With a widespread distribution in the nervous system, TRPM7 is involved in animal behaviors and neuronal death induced by ischemia. However, the physiological role of TRPM7 in central nervous system (CNS) neuron remains unclear. Here, we identify endocytic defects in neuroendocrine cells and neurons from TRPM7 knockout (KO) mice, indicating a role of TRPM7 in synaptic vesicle endocytosis. Our experiments further pinpoint the importance of TRPM7 as an ion channel in synaptic vesicle endocytosis. Ca2+ imaging detects a defect in presynaptic Ca2+ dynamics in TRPM7 KO neuron, suggesting an importance of Ca2+ influx via TRPM7 in synaptic vesicle endocytosis. Moreover, the short-term depression is enhanced in both excitatory and inhibitory synaptic transmissions from TRPM7 KO mice. Taken together, our data suggests that Ca2+ influx via TRPM7 may be critical for short-term plasticity of synaptic strength by regulating synaptic vesicle endocytosis in neurons.

3.
Int J Gen Med ; 14: 5333-5343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522130

RESUMO

Background: The early symptoms of patients with elevated intracranial pressure (ICP) after intracerebral hemorrhage (ICH) are easily overlooked, which will result in missing the optimal opportunity for clinical intervention. However, it is difficult for ICH patients admitted to the neurology department to receive invasive ICP monitoring, although it is crucial for the early identification of neurologic deterioration (ND). Objective: The aim of this study is to investigate the association between the changes of transcranial Doppler (TCD) variables and ND after onset and establish a nomogram for predicting the short-term outcome of ICH. Methods: A total of 297 patients were recruited and their clinical characteristics and the changes of TCD variables were recorded. The independent prognostic factors for the ND after onset in the ICH patients were screened from multivariate Logistic regression analysis, which were served as inputs for the nomogram construction. Discrimination and calibration validations were performed to assess the performance of the nomogram [concordance index (C-index) for discrimination and Hosmer-Lemeshow (HL) test for calibration] and the decision curve analysis was applied to assess the clinical suitability. Results: ΔaPI [defined as the change of pulsatility index (PI) between the 1st and 3rd day after onset for affected hemisphere] was independently associated with the ND after onset. Moreover, hematoma volume, presence of intraventricular hemorrhage, and Glasgow coma scale were also the independent prognostic factors of ND. The developed nomogram incorporating ΔaPI showed good discrimination (C-index: 0.916 after 1000 bootstrapping) and calibration (P=0.412, HL test) and yielded net benefits. Conclusion: The nomogram incorporating ΔaPI might be useful in predicting the risk of ND within 14 days after onset, which might help identify patients in the neurology department in need of further care.

4.
J Thorac Dis ; 13(7): 4033-4042, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34422333

RESUMO

Background: Lymph node metastasis (LNM) status can be a critical decisive factor for clinical management of lung cancer. Accurately evaluating the risk of LNM during or after the surgery can be helpful for making clinical decisions. This study aims to incorporate clinicopathological characteristics to develop reliable machine learning (ML)-based models for predicting LNM in patients with early-stage lung adenocarcinoma. Methods: A total of 709 lung adenocarcinoma patients with tumor size ≤2 cm were enrolled for analysis and modeling by multiple ML algorithms. The receiver operating characteristic (ROC) curve and decision curve were used for evaluating model's predictive performance and clinical usefulness. Feature selection based on potential models was performed to identify most-contributed predictive factors. Results: LNM occurred in 11.3% (80/709) of patients with lung adenocarcinoma. Most models reached high areas under the ROC curve (AUCs) >0.9. In the decision curve, all models performed better than the treat-all and treat-none lines. The random forest classifier (RFC) model, with a minimal number of five variables introduced (including carcinoembryonic antigen, solid component, micropapillary component, lymphovascular invasion and pleural invasion), was identified as the optimal model for predicting LNM, because of its excellent performance in both ROC and decision curves. Conclusions: The cost-efficient application of RFC model could precisely predict LNM during or after the operation of early-stage adenocarcinomas (sensitivity: 87.5%; specificity: 82.2%). Incorporating clinicopathological characteristics, it is feasible to predict LNM intraoperatively or postoperatively by ML algorithms.

5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(3): 225-229, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34374231

RESUMO

Objective: To investigate the relationship between mitochondrial DNA (mtDNA) variation and high altitude essential hypertension(HAEH) in the Chinese Tajik population. Methods: Fifty-three patients with HAEH and 46 healthy subjects were enrolled from the Chinese Tajik population. The mtDNA fragments were amplificated by polymerase chain reaction, and products were sequenced to acquire full sequence of mtDNA. The mtDNA sequences of all subjects were compared to the Cambridge sequence to explore mtDNA variations and analyze difference between HAEH and healthy controls. Online softwares were applied to predict function changes caused by positive associated mtDNA variations. Results: Compared to the control group, the frequency of haplogroup U4b was significant higher in HAEH group(P=0.023,OR=7.062,CI(95%)=1.306-38.182), and the frequencies of 8 mutations from haplogroup U4b showed a significant difference between the HAEH group and control group (all with P values below 0.05). The mt DNA15693T>C mutation was the only missense mutation, which affected amino acid 316 in mitochondrial cytochrome b (MTCYB) by changing it from methionine to threonine. Bioinformatics analysis indicated that the mutation in MTCYB may play a biological role through affecting the second structure of protein. Conclusion: MtDNA subhaplogroup U4b is a genetic factor for HAEH in the Chinese Tajik population, and mtDNA15693T>C mutation may be an important molecular mechanism of HAEH.


Assuntos
DNA Mitocondrial , Predisposição Genética para Doença , Altitude , Grupo com Ancestrais do Continente Asiático/genética , China , DNA Mitocondrial/genética , Hipertensão Essencial/genética , Haplótipos , Humanos , Mutação
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(4): 343-348, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34374251

RESUMO

Objective: To analyze the long non-coding RNA (lncRNA) and messenger RNA (mRNA) co-expression network changes induced by mtDNA3010A/G mutation in acute hypoxia, and to investigate the role of key lncRNA and mRNA in the regulation of gene expression induced by hypoxia. Methods: The genotype combinations A-C-C and G-C-C of mitochondrial DNA 3010-5178-10400 were screened, and genotypes of mtDNA3010A and mtDNA3010G fusion cells were constructed by using osteosarcoma cell treated by ethidium bromide without mitochondrion (ρ0206 cell) as donors. After treatment with 1% O2 24 h, the lncRNA - mRNA expression chip was applied to detect the differently expressed lncRNA and mRNA in two kinds of fusing cells, and fluorescence quantitative polymerase chain method was used to verify differently expressed mRNA. Bioinformatics methods were applied to build co-expression network of lncRNA-mRNA, predict target genes of differently expressed lncRNA, and the functions of differently expressed mRNA and target genes predicted by lncRNA were also analyzed based on gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) forecast analysis. Results: After treatment with 1% O2 for 24 h, compared with mtDNA3010G fusion cells: 688 lncRNAs were up-regulated, 21 were more than 2 times; 1098 were down-regulated, and 4 were more than 2 times. There were 1151 mRNA expressions up-regulated, 14 were more than 2 times, 539 mRNA expressions were down-regulated, and 3 were more than 2 times. Conclusion: MtDNA3010A/G genotype mutation under hypoxia is able to affect the lncRNA-mRNA regulatory network, and the differentially expressed lncRNA and mRNA may play an important role in regulation network of gene expression induced by hypoxia, which is expected to be a target for the regulation of hypoxia reaction from the perspective of mitochondria.


Assuntos
RNA Longo não Codificante , Perfilação da Expressão Gênica , Genótipo , Humanos , Hipóxia/genética , Mutação , RNA Longo não Codificante/genética , RNA Mensageiro/genética
7.
ChemMedChem ; 16(19): 2960-2968, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34235861

RESUMO

Multivalent antibody-recruiting glycopolymers (MARGs) composed of hyaluronic acid (HA) grafted with multiple copies of dinitrophenol (DNP) were developed for targeted cancer immunotherapy. Structure-activity studies demonstrated that the MARGs were able to specifically recognize CD44-positive cancer cells and displayed remarkable antibody-recruiting capacities and tumor cell killing activities dependent on the introduced multivalent effect and the length of PEG linker. One of the MARGs, HA-[PEG3 -DNP]8 , showed the best capacity for clustering anti-DNP antibodies onto CD44-positive cancer cells and displayed potent in vitro anti-cancer activity by triggering complement dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, we found that HA-[PEG3 -DNP]8 significantly inhibited the xenograft tumor growth of Babl/c nude mice bearing triple negative breast cancer cells, while it did not cause detectable histological cytotoxicity. Given the easy access of this type of natural glycopolymer and the practical synthesis approach, these MARGs provide promising immunotherapeutics for cancer immunotherapy.

8.
Food Chem ; 365: 130534, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34256224

RESUMO

Active food packaging materials containing procyanidins (PC) exhibits outstanding antimicrobial activity, but PC is easy to be hydrolyzed by acid. A novel water-soluble chitosan (CS)-based copolymer was prepared to be used as a carrier to provide a pH-stable environment for loading PC. CS was copolymerized with polyvinyl alcohol (PVA) via a coupling reagent-mediated approach. The CS-graft-PVA film exhibited a desirable PC encapsulation efficiency of over 95% and excellent long-term release sustainability, which was better than the conventional CS and CS-blend-PVA films. Moreover, CS-graft-PVA film had satisfactory mechanical properties and barrier properties, as well possessed a desirable antibacterial activity and biofilm inhibition against foodborne pathogenic microbes and spoilage bacteria. The film was also applied in the salmon muscle perseveration and showed a potential ability to prevent microorganism contamination and texture deterioration in 10 days. These results suggested that the CS-graft-PVA film has an excellent promise for future food packaging applications.


Assuntos
Anti-Infecciosos , Quitosana , Proantocianidinas , Antibacterianos/farmacologia , Embalagem de Alimentos , Álcool de Polivinil
9.
Phytomedicine ; 90: 153641, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34281775

RESUMO

BACKGROUND: Neurodegenerative diseases are becoming increasingly prevalent over the world. Therefore, drug development in this field is urgently required. Neuron impairment leads to the pathogenesis of neurodegenerative diseases, while amelioration of oxidative stress can inhibit the impairment. As a traditional Chinese medicine, mulberry leaf exhibits various pharmacological properties, including neuroprotective activity. But the major components responsible for the neuroprotective activity of mulberry leaf remained unknown. Phytochemicals were potent candidates of neuroprotective drug. Prenylated phenolics are the leading phytochemicals present in mulberry leaf. PURPOSE: The aim of this study was to investigate the neuroprotective activities and mechanisms of prenylated phenolics. METHODS: The chemical structure of isolated compounds were elucidated by MS and NMR. UPLC-MS/MS was used to determine the contents of prenylated phenolics in fresh mulberry leaf. Neurotoxicity was induced by erastin in HT22 cells. CCK-8 assay was performed to assess cell viability. ROS production, GSH level and iron release were monitored by using DCFH-DA, monobromobimane, and FeRhoNox™-1, respectively. qRT-PCR and Western blotting assays were performed to assess gene and protein expression, respectively. RESULTS: Four prenylated phenolics, including isobavachalcone, morachalcone B, moracin N and morachalcone A were isolated and identified from mulberry leaf. Their levels in fresh mulberry leaf were in a decreasing order, moracin N > morachalcone A > morachalcone B > isobavachalcone. Moreover, moracin N showed a good neuroprotective activity with an EC50 < 0.50 µM. The neuroprotective mechanisms of moracin N included inhibition of glutathione depletion, glutathione peroxidase 4 (GPx4) inactivation, reactive oxygen species (ROS) overproduction and iron accumulation, as well as improvement of intracellular antioxidant enzyme activities. Moracin N augmented the transcriptional levels of genes involved in antioxidant defense and glutathione biosynthesis in the early state of ferroptosis induction, and downregulated expression of genes related to iron accumulation and lipid peroxidation. CONCLUSION: The results confirmed that moracin N was a good ferroptosis inhibitor, which exerted neuroprotective activity through preventing from oxidative stress.


Assuntos
Morus , Fármacos Neuroprotetores/farmacologia , Fenóis , Animais , Linhagem Celular , Cromatografia Líquida , Camundongos , Morus/química , Fenóis/farmacologia , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Espectrometria de Massas em Tandem
10.
Front Oncol ; 11: 704067, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34222028

RESUMO

Although integrin subunit genes (ITGs) have been reported to be associated with some human cancer types, a systematic assessment of ITGs across human cancers is lacking. Hence, we performed comprehensive analyses to investigate mRNA expression, copy number variation (CNV), DNA methylation, mutation, and clinical landscapes of ITGs in more than 8000 cancer patients from The Cancer Genome Atlas (TCGA) dataset. Landscapes of ITGs were established across 20 human cancer types. We observed that ITGs are extensively dysregulated with heterogeneity in different system cancer types, part of which are driven by CNV, DNA hypomethylation or mutation. Furthermore, dysregulated prognosis-related ITGs were systematically identified in each cancer type, including ITGA11 in stomach adenocarcinoma (STAD). The models based on dysregulated ITGs with clinical relevance and TNM staging indexes are good indicators in STAD and head and neck squamous cell carcinoma. Finally, ITGA11 is overexpressed and associated with poor survival in STAD cases from the TCGA and additionally Gene Expression Omnibus cohorts. Functionally, ITGA11 knockdown inhibits malignant phenotypes in STAD cell lines AGS and MKN45, demonstrating the oncogenic role of ITGA11 in STAD. Together, this study highlights the important roles of ITGs in tumorigenesis as potential prognostic biomarkers, and provide an effective resource that identifies cancer-related genes of ITGs in human cancers.

11.
Biomolecules ; 11(5)2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066441

RESUMO

Hypertriglyceridemia-associated acute pancreatitis (HTGAP) is linked with increased severity and morbidity. Intestinal flora plays an important role in the progression of acute pancreatitis (AP). However, pathogenetic association between gut microbiota and HTGAP remains unknown. In this study, we enrolled 30 HTGAP patients and 30 patients with AP that is evoked by other causes. The V3-V4 regions of 16S rRNA sequences of the gut microbiota were analyzed. Clinical characteristics, microbial diversity, taxonomic profile, microbiome composition, microbiological phenotype, and functional pathways were compared between the two groups. Our results showed that the HTGAP group had a higher proportion of severe AP (46.7% vs. 20.0%), organ failure (56.7% vs. 30.0%), and a longer hospital stay (18.0 days vs. 6.5 days). HTGAP group also had poorer microbial diversity, higher abundances of Escherichia/Shigella and Enterococcus, but lower abundances of Dorea longicatena, Blautia wexlerae, and Bacteroides ovatus as compared with non-HTGAP group. Correlation analysis revealed that gut bacterial taxonomic and functional changes were linked with local and systemic complications, ICU admission, and mortality. This study revealed that alterations of gut microbiota were associated with disease severity and poor prognosis in HTGAP patients, indicating a potential pathophysiological link between gut microbiota and hypertriglyceridemia related acute pancreatitis.


Assuntos
Bactérias/classificação , Hipertrigliceridemia/microbiologia , Pancreatite/mortalidade , RNA Ribossômico 16S/genética , Análise de Sequência de DNA/métodos , Adulto , Idoso , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/genética , DNA Ribossômico/genética , Feminino , Microbioma Gastrointestinal , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pancreatite/microbiologia , Filogenia , Prognóstico , Estudos Prospectivos , Índice de Gravidade de Doença
12.
Front Neurosci ; 15: 678465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093121

RESUMO

Background: Mental syndromes such as anxiety and depression are common comorbidities in patients with chronic insomnia disorder (CID). The locus coeruleus noradrenergic (LC-NE) system is considered to be crucial for modulation of emotion and sleep/wake cycle. LC-NE system is also a critical mediator of the stress-induced anxiety. However, whether the LC-NE system contributes to the underlying mechanism linking insomnia and these comorbidities remain unclear. This study aimed to investigate the LC-NE system alterations in patients with insomnia and its relationship with depression and anxiety symptoms. Materials and Methods: Seventy patients with CID and 63 matched good sleep control (GSC) subjects were recruited and underwent resting-state functional MRI scan. LC-NE functional network was constructed by using seed-based functional connectivity (FC) analysis. The alterations in LC-NE FC network in patients with CID and their clinical significance was explored. Results: Compared with GSC group, the CID group showed decreased left LC-NE FC in the left inferior frontal gyrus, while they had increased LC-NE FC in the left supramarginal gyrus and the left middle occipital gyrus (MOG). For the right LC-NE FC network, decreased FC was found in left dorsal anterior cingulate cortex (dACC). Interesting, the increased LC-NE FC was located in sensory cortex, while decreased LC-NE FC was located in frontal control cortex. In addition, the FC between the left LC and left MOG was associated with the duration of the disease, while abnormal FC between right LC and left dACC was associated with the anxiety scores in patients with CID. Conclusion: The present study found abnormal LC-NE functional network in patients with CID, and the altered LC-NE function in dACC was associated with anxiety symptoms in CID. The present study substantially extended our understanding of the neuropathological basis of CID and provided the potential treatment target for CID patients who also had anxiety.

13.
Trials ; 22(1): 386, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34098994

RESUMO

BACKGROUND: Many patients with chronic insomnia disorder (CID) have gastrointestinal (GI) symptoms. First-line insomnia medications do not treat GI problems. Acupuncture has a comprehensive regulative action on both CID and GI disorder and is receiving increasing attention. Recent studies indicate that both CID and GI diseases may cause abnormal brain activity. However, the neurological mechanism underlying the effect of acupuncture on such diseases is still unclear. The aim of this study is to explore the pathological mechanisms of CID with GI discomfort, as well as the main response characteristics of acupuncture treatment from multiple perspectives using multimodal magnetic resonance imaging (MRI). METHODS: A total of 60 participants with CID and GI disorders will be randomly divided into two groups (real acupuncture group and sham acupuncture group; ratio of 1:1). Patients will receive 20 sessions (five sessions per week) of real acupuncture treatment or sham acupuncture treatment. The primary outcome is the aggregate score on the Pittsburgh Sleep Quality Index. Secondary outcomes are scores on the Gastrointestinal Symptom Rating Scale, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. Multimodal MRI scans and clinical assessments will be performed both at baseline and post-treatment. Another 30 age-, sex-, and education-matched healthy subjects will be recruited as controls and will receive MRI scans and clinical evaluations. DISCUSSION: This study aims to provide scientific evidence for the mechanism of acupuncture in treating CID with GI disorder using multimodal MRI imaging data on brain structure, function, and metabolism. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800017092 (URL: http://www.chictr.org.cn/showproj.aspx?proj=27173 ). Registered on July 11, 2018.


Assuntos
Terapia por Acupuntura , Gastroenteropatias , Distúrbios do Início e da Manutenção do Sono , Encéfalo/diagnóstico por imagem , Gastroenteropatias/diagnóstico por imagem , Gastroenteropatias/terapia , Humanos , Imageamento por Ressonância Magnética , Ensaios Clínicos Controlados Aleatórios como Assunto , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do Tratamento
14.
Ann Clin Lab Sci ; 51(3): 368-375, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34162567

RESUMO

OBJECTIVE: The WNT pathway might be the primary pathway for the regulation of renal development by PAX2. In this study, we aimed to observe the migration and invasion abilities of human tubular epithelial cells stably transfected with PAX2 upon the WNT pathway blockade and to investigate whether the WNT pathway is involved in the regulation of cellular biological activity by PAX2. METHODS: 1. Control cells-PAX2 and control cells+PAX2 groups were formed for monitoring the expression of PAX2 and ß-catenin mRNA using RT-qPCR. 2. The PAX2-expressing cells were treated with WIF-1 (5 µg/ml), WIF-1 (10 µg/ml), or WIF-1 (15 µg/ml), and the effect was analyzed by Western blotting analysis after the WNT pathway blockade. 3. The migration and invasion abilities of the PAX2-expressing cells were evaluated using cell-scratch and transwell assays after blocking the WNT pathway. RESULTS: 1. RT-qPCR: The expression of PAX2 and ß-catenin increased significantly in the PAX2-expressing cells (P<0.05). 2. Upon treatment with WIF-1, the expression of ß-catenin in the PAX2 cells+WIF-1 5 µg/ml group, PAX2 cells+WIF-1 10µg/ml group, and PAX2 cells+WIF-1 15 µg/ml group decreased significantly compared to in the PAX2 cells-WIF-1 group (P<0.05), especially the WIF-1 (15 µg/ml) group (P<0.05). 3. The cell migration rate in the PAX2 cells + WIF-1 (15 µg/ml) group at 18 h was significantly lower than that in the PAX2 cells-WIF-1 group (P<0.05). 3. Transwell assay: the invasion ability in the PAX2 cells+WIF-1 (15 µg/ml) group was lower than that in the PAX2 cells-WIF-1 group (P<0.05). CONCLUSION: WNT pathway blockade can weaken the migration and invasion abilities of PAX2-expressing cells. Moreover, the WNT pathway was observed to be associated with the regulation of cellular biological activity by PAX2.

15.
Chem Sci ; 12(12): 4623-4630, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-34163726

RESUMO

Developing monoclonal antibodies (mAbs) for cancer immunotherapy is expensive and complicated. Nanobodies are small antibodies possessing favorable pharmacological properties compared with mAbs, but have limited anticancer efficacy due to the lack of an Fc region and poor pharmacokinetics. In this context, engineered universal endogenous antibody-recruiting nanobodies (UEAR Nbs), as a general and cost-effective approach, were developed to generate functional antibody-like nanobodies that could recapitulate the Fc biological functions for cancer immunotherapy. The UEAR Nbs, composed of the IgG binding domain and nanobody, were recombinantly expressed in E. coli and could recruit endogenous IgGs onto the cancer cell surface and trigger potent immune responses to kill cancer cells in vitro. Moreover, it was proved that UEAR Nbs displayed significantly improved half-lives in vivo. The in vivo antitumor efficacy of UEAR Nbs was demonstrated in a murine model using EGFR positive triple-negative breast cancer (TNBC).

16.
Exp Cell Res ; 404(2): 112593, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33961841

RESUMO

AIMS: Acute lung injury (ALI) is a leading cause of mortality as a result of inflammatory cytokine overexpression and increased rates of apoptosis. Therapies for ALI are yet to be thoroughly investigated. Recent evidence has shown that irisin exerts protective effects against many types of pathologies. The present study aimed to determine the function of irisin in an ALI mouse model induced by lipopolysaccharide (LPS) and the corresponding underlying mechanisms at the tissue, cellular, and molecular levels. MAIN METHODS: We assessed irisin function in A549 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays. The cell apoptosis was evaluated by flow cytometry. Western blotting and RT-PCR were used to test expression level. Animal models of ALI was established. KEY FINDINGS: We found that irisin treatment maintained lung weight, significantly reduced inflammatory cytokine expression, and alleviated lung injury by downregulating miR-199a. In LPS-stimulated cells, forced miR-199a expression downregulated Rad23b expression by targeting its 3' untranslated region, indicating that Rad23b is a direct target of miR-199a. SIGNIFICANCE: These findings reveal that irisin can alleviate ALI by inhibiting miR-199a and upregulating Rad23b expression, suggesting that irisin has clinical potential for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fibronectinas/farmacologia , MicroRNAs/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Proteínas de Ligação a DNA/efeitos dos fármacos , Modelos Animais de Doenças , Fibronectinas/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
17.
Ann Palliat Med ; 10(5): 5425-5432, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33977755

RESUMO

BACKGROUND: Acute atelectasis is common after traumatic brain injury (TBI), but the related factors and treatment are still unclear. This study is to analyze the independent risk factors for acute atelectasis after TBI and propose an interventional nursing strategy, in order to correct respiratory function and improve the prognosis of patients. METHODS: The clinical data of 93 patients with TBI admitted to our hospital from April 2015 to October 2019 were retrospectively analyzed. Clinical data were analyzed by single factor analysis, the cutoff value of influencing factors was obtained by receiver operating characteristic (ROC) curve analysis, and the influencing factors for acute atelectasis after TBI were examined by multi-factor logistic regression. RESULTS: Twenty-two patients (23.66%) were complicated with acute atelectasis during the observation period, while the remaining 71 patients (76.34%) did not have acute atelectasis. Univariate analysis showed that there were significant differences in the Glasgow Coma Scale (GCS), history of vomiting and aspiration, mannitol use, mechanical ventilation, hypoalbuminemia, and serum hypoxia-inducible factor-1α (HIF-1α) between the acute atelectasis group and the non-acute atelectasis group (P<0.05). The AUC area of HIF-1α level predicting acute atelectasis was 0.896 [95% confidence interval (CI): 0.814-0.978, P=0.042], and the cut-off value was 2.12 mmol/L, with a sensitivity of 76.9% and a specificity of 93.3%. Logistic regression analysis showed that a history of vomiting and aspiration [odds ratio (OR) 3.908, 95% confidence interval (CI): 1.201-12.712], mechanical ventilation (OR 3.250, 95% CI: 1.139-9.271), hypoalbuminemia (OR 5.741, 95% Cl: 1.926-17.113), and HIF-1α ≥2.12 mmol/L (OR 6.623, 95% CI: 2.364-16.346) were independent risk factors for acute atelectasis after TBI. CONCLUSIONS: A history of vomiting and aspiration, mechanical ventilation, hypoalbuminemia, and high expression of HIF-1α are all independent risk factors for postoperative acute atelectasis in patients with TBI. In clinical practice, patients should be guided to swallow properly, breathe smoothly, eat well, and regularly check the relevant indexes.


Assuntos
Lesões Encefálicas Traumáticas , Atelectasia Pulmonar , Lesões Encefálicas Traumáticas/complicações , Humanos , Prognóstico , Atelectasia Pulmonar/etiologia , Estudos Retrospectivos , Fatores de Risco
18.
Cancer Cell ; 39(5): 694-707.e7, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33836152

RESUMO

Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.

19.
ChemMedChem ; 16(16): 2426-2440, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-33780139

RESUMO

With the advantage of inherent responsiveness that can change the spectroscopic signals from "off" to "on" state in responding to targets (e. g. biological analytes/microenvironmental factors), activatable fluorescent probes have attracted extensive attention and made significant progress in the field of bioimaging and biosensing. Due to the high depth of tissue penetration, minimal tissue damage and negligible background signal at longer wavelengths, the development of second near-infrared window (NIR-II) fluorescent materials provides a new opportunity to develop activable fluorescent probes. Here, we summarized properties, advantages and disadvantages of mainly NIR-II fluorophores (such as rare earth-doped nanoparticles, quantum dots, single-walled carbon nanotubes, small molecule dyes, conjugated polymers and gold nanoclusters), then overviewed current role and development of activatable NIR-II fluorescent probes (AFPs) for biomedical applications including biosensing, bioimaging and therapeutic. The potential challenges and perspectives of AFPs in deep-tissue imaging and clinical application are also discussed.

20.
Future Oncol ; 17(16): 2005-2013, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33784826

RESUMO

Background: Previous researches had not proposed any prediction models for occult lymph node metastasis (OLNM). Considering the occurrence of OLNM and the importance of OLNM management, we aimed to develop a nomogram to predict OLNM of patients with lung adenocarcinoma ≤2 cm. Methods: Characteristics of patients with lung adenocarcinoma of ≤2 cm diameter at the Peking Union Medical College Hospital were retrospectively reviewed. Univariate and multivariate logistic regressions were performed. A nomogram model was developed. The concordance index (C-index) and calibration and decision curves were used to evaluate the predictive ability. Results: A total of 473 patients were enrolled, with an OLNM incidence of 7.4%. Four factors were selected as risk factors. The model had a C-index of 0.932. Calibration and decision curves were determined. Conclusion: Patients with pure ground-glass opacity (pGGO) or noninvasive adenocarcinoma have significantly lower risk of OLNM. SUVmax, CEA, micropapillary and solid component were identified as independent risk factors. The nomogram model was effective in predicting OLNM preoperatively.

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