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Cardiac hypertrophy is an adaptive response to stressors such as high cardiac workload, which might lead to abnormal cardiac function and heart failure. Previous studies have indicated that macrophage migration inhibitory factor (MIF) might play a protective role in cardiac hypertrophy. Here, we aimed to illustrate the mechanism of MIF in protecting against pressure overload-induced cardiac hypertrophy. Transverse aortic constriction (TAC) mouse model was established and we found that overexpression of MIF protected against pressure overload-induced cardiac hypotrophy in TAC treated mice, as evidenced by significantly decreased the heart weight. In addition, transthoracic echocardiography showed that overexpression of MIF restored ejection fraction in TAC-treated mice. While TAC treatment resulted in a much larger cardiomyocyte size in mice, MIF overexpression notably decreased the cardiomyocyte size. Next, we demonstrated that MIF overexpression promoted the expression of miR-29b-3p which further downregulated the expression of its downstream target HMG box protein 1 (HBP1). Overexpression of HBP1 reversed the effect of MIF in alleviating Ang-II induced oxidative stress in cardiomyocytes. In conclusion, our findings suggest that MIF could attenuate pressure overload-induced cardiac hypertrophy through regulating the miR-29b-3p/HBP1 axis.
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Cardiomegalia , Fatores Inibidores da Migração de Macrófagos , Camundongos Endogâmicos C57BL , MicroRNAs , Miócitos Cardíacos , Animais , Masculino , Camundongos , Cardiomegalia/metabolismo , Cardiomegalia/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Oxirredutases Intramoleculares , Fatores Inibidores da Migração de Macrófagos/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Miócitos Cardíacos/metabolismo , Estresse OxidativoRESUMO
Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.
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Acne Vulgar , Lasers de Gás , Masculino , Feminino , Humanos , Cicatriz/patologia , Dióxido de Carbono , Resultado do Tratamento , Acne Vulgar/complicações , Eritema/etiologia , Lasers de Gás/uso terapêutico , Atrofia/complicaçõesRESUMO
Diabetes mellitus (DM) is a metabolic disease with multiple complications, including diabetic cutaneous wounds, which lacks effective treating strategies and severely influences the patients' life. Endothelial progenitor cells (EPCs) are reported to participate in maintaining the normal function of blood vessels, which plays a critical role in diabetic wound healing. TLQP-21 is a VGF-derived peptide with promising therapeutic functions on DM. Herein, the protective effects of TLQP-21 on diabetic cutaneous wound and the underlying mechanism will be investigated. Cutaneous wound model was established in T2DM mice, followed by administering 120 nmol/kg and 240 nmol/kg TLQP-21 once a day for 12 days. Decreased wound closure, reduced number of capillaries and EPCs, declined tube formation function of EPCs, and inactivated PI3K/AKT/eNOS signaling in EPCs were observed in T2DM mice, which were sharply alleviated by TLQP-21. Normal EPCs were extracted from mice and stimulated by high glucose (HG), followed by incubated with TLQP-21 in the presence or absence of LY294002, an inhibitor of PI3K. The declined cell viability, increased apoptotic rate, reduced number of migrated cells, declined migration distance, repressed tube formation function, and inactivated PI3K/AKT/eNOS signaling observed in HG-treated EPCs were markedly reversed by TLQP-21, which were dramatically abolished by the co-culture of LY294002. Collectively, TLQP-21 facilitated diabetic wound healing by inducing angiogenesis through alleviating HG-induced injuries on EPCs.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Glucose , Neovascularização Fisiológica , Proteínas Proto-Oncogênicas c-akt , Cicatrização , Animais , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Cicatrização/efeitos dos fármacos , Masculino , Neovascularização Fisiológica/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Óxido Nítrico Sintase Tipo III/metabolismo , Transdução de Sinais/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Fosfatidilinositol 3-Quinases/metabolismo , Fragmentos de Peptídeos/farmacologia , Células Cultivadas , AngiogêneseRESUMO
Oil exploitation may pose adverse effects on marine ecosystems, but its impacts on surface carbonate dynamics remain unknown. In a carbonate system with low air-sea ∆pCO2, such as the South China Sea (SCS), human activities may affect the pCO2 distribution patterns and potentially alter CO2 sink or source at the surface. This study investigates the surface carbonate system in two oil fields, namely the Wenchang Oil Feld and Enping Oil Feld, located on the northwestern SCS (NWSCS) shelf. In Enping Oil Field, although there is a slight increase in surface pCO2 due to probable total alkalinity (TA) consumption from CaCO3 precipitation, strong biological production makes the plume water a strong CO2 sink. Similarly, the biological processes dominated the pCO2 variability in Wenchang Oil Feld, exhibiting high values in its central area. In NWSCS, the influence of shelf water was observed during both cruises. And the pCO2 drawdown caused by the decreased sea surface temperature (SST) and CO2 outgassing outweighed their increases via enhanced vertical mixing, leading to a pCO2 drawdown from September to October within this water mass. More importantly, there were no significant disparities observed in carbonate parameters at stations along transects with and without wells, and the observed parameter values in this study fell within the range reported previously on the nSCS shelf with similar controlling processes. Thus the impact of oil exploitation on carbonate dynamics is negligible, and the characteristics of the carbonate system in oil field are primarily governed by natural processes such as the mixing of plume water and basin water, CaCO3 precipitation and the changes in SST. The provided data establish a crucial baseline for detecting future alterations in carbonate chemistry within oil fields, and the rapid fluctuations in sea surface pCO2 highlight the need for higher spatiotemporal resolution observation.
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The mammary gland is an adipose tissue containing not only adipocytes but also epithelial, endothelial, and immune cells. Epithelial cells and macrophages, as the integral components of the immune system, are on the front line of defense against infection. Our preliminary work proved that caffeic acid (CA) can effectively inhibit the inflammatory cascade of bovine mammary epithelial cells (BMEC) induced by lipopolysaccharide (LPS) and maintain cellular integrity and viability. Here, we investigated the therapeutic effect of CA on LPS-induced mice mastitis and explored its regulatory mechanism on macrophage inflammatory response induced by LPS in vitro. Firstly, the mice mastitis model was established by intramammary injection with 10 µg LPS, after which different CA doses (5, 10, 15 mg/kg) were administered. Then, the pathological section, myeloperoxidase (MPO) activity, proinflammatory factors and chemokines releasement, and redox state of mammary tissues were assessed, confirming CA's effectiveness on mice mastitis. In vitro, we validated the therapeutic relevance of CA in relieving LPS-induced RAW264.7 inflammatory and oxidative stress responses. Moreover, we further provided evidence that CA significantly reduced LPS-induced reactive oxygen species (ROS) generation via NADPH oxidase (NOX), which improved the imbalance relationship between nuclear factor kappa-B (NF-κB) and NF-E2 p45-related factor 2 (Nrf2) and led to a marked weakening of M1 polarization. The NOX-ROS signal inhibited by CA weakened the oxidative burst and neutrophil chemotaxis of macrophages, thus alleviating the immune cascade in mammary gland tissue and reducing the LPS-induced inflammatory damage. Collectively, CA would be a potential candidate or antibacterial synergist for curbing mastitis.
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Lipopolissacarídeos , Mastite , Humanos , Feminino , Animais , Bovinos , Camundongos , Lipopolissacarídeos/efeitos adversos , Espécies Reativas de Oxigênio , NADPH Oxidases , Mastite/induzido quimicamente , Mastite/tratamento farmacológico , NF-kappa B , Modelos Animais de Doenças , Macrófagos , Células EpiteliaisRESUMO
BACKGROUND: Although several procedures of subclavian venipuncture have been reported, no standard method has been established yet. The purpose of this study was to investigate some more accurate and improved blind puncture tips. METHODS: A prospective study was conducted on patients who underwent cardiac radio-frequency ablation with the blind technique of subclavian venipuncture from August 2018 to June 2022. All patients were randomly assigned to an intrathoracic approach group or extrathoracic approach group. Each group of patients followed their own specific puncture scheme and tips. RESULTS: About 371 punctures were included. Blind subclavian venipunctures were performed with 98.9% technical success and without complications in all patients. The over-all success rate with an intrathoracic and extrathoracic approach was equivalent (96.7% vs. 98.3%, P =.23). The intrathoracic group showed a higher first-pass success compared with the extrathoracic group (91.9% vs. 80.2%, P = 0.003, respectively). CONCLUSION: We localized the landmark/reference and skin puncture site of an intrathoracic and extrathoracic subclavian venipuncture individually and quantitatively. These experiences make blind techniques more accurate and faster.
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Punções , Veia Subclávia , Humanos , Veia Subclávia/diagnóstico por imagem , Veia Subclávia/cirurgia , Estudos Prospectivos , Punções/métodos , Flebotomia/métodosRESUMO
Regulated pyroptosis is critical for pathogen elimination by inducing infected cell rupture and pro-inflammatory cytokines secretion, while overwhelmed pyroptosis contributes to organ dysfunction and pathological inflammatory response. Caffeic acid (CA) and ferulic acid (FA) are both well-known antioxidant and anti-inflammatory phenolic acids, which resemble in chemical structure. Here we found that CA, but not FA, protects macrophages from both Nigericin-induced canonical and cytosolic lipopolysaccharide (LPS)-induced non-canonical pyroptosis and alleviates LPS-induced mice sepsis. It significantly improved the survival of pyroptotic cells and LPS-challenged mice and blocked proinflammatory cytokine secretion. The anti-pyroptotic effect of CA is independent of its regulations in cellular lipid peroxidation, mitochondrial function, or pyroptosis-associated gene transcription. Instead, CA arrests pyroptosis by directly associating with gasdermin D (GSDMD) and blocking its processing, resulting in reduced N-GSDMD pore construction and less cellular content release. In LPS-induced septic mice, CA inhibits GSDMD activation in peritoneal macrophages and reduces the serum levels of interleukin-1ß and tumor necrosis factor-α as the known pyroptosis inhibitors, disulfiram and dimethyl fumarate. Collectively, these findings suggest that CA inhibits pyroptosis by targeting GSDMD and is a potential candidate for curbing the pyroptosis-associated disease.
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BACKGROUND: The study aimed to investigate the diagnostic efficiency of human neutrophil lipocalin (HNL) in bacterial infections in children. METHODS: This study included 49 pediatric patients with bacterial infections, 37 patients with viral infections, 30 patients with autoimmune diseases (AID) and 41 healthy controls (HCs). HNL, procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC) and neutrophil counts were detected in the initial diagnosis and the following days. RESULTS: In the patients with bacterial infections, the levels of HNL, PCT, CRP, WBC and neutrophils were significantly increased than that of disease controls and HCs. The dynamic of these markers was monitored during antibiotic treatment. The level of HNL was decreased rapidly in patients with effective treatment, but maintained at high levels in deteriorated patients according to the clinical progression. CONCLUSIONS: HNL detection is an effective biomarker to identify bacterial infections from viral infections and other AIDs, and has potential value to evaluate the effect of antibiotic treatment in pediatric patients.
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Infecções Bacterianas , Viroses , Humanos , Criança , Lipocalinas/metabolismo , Neutrófilos/metabolismo , Biomarcadores , Proteína C-Reativa , Infecções Bacterianas/microbiologia , Viroses/diagnóstico , Pró-CalcitoninaRESUMO
OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.
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The evaluation of island carrying capacity is the premise for conducting the island spatial planning and can contributes to guiding island ecological conservation and socioeconomic developments. In this study, the island carrying capacities were evaluated for the three major development types, namely, ecological resource, agricultural production, and urban construction, based on the quantity and quality. The occupancy and vacancy rates of island carrying capacity were measured in different scenarios. Miaodao Archipelago and Dongtou Archipelago in China were selected as the study area to demonstrate the evaluation. The former is constituted all by spatially isolated rocky islands, while the latter is featured by the coexistence of the sandy and rocky islands and the connection with the mainland by bridges. The results indicated the high variances of occupancy and vacancy rates of island carrying capacity at multiple spatial scales. Across the two archipelagos, climate conditions, island composition, and spatial connections with the mainland controlled the spatial variance at this scale. For different types of islands, the sandy island presented distinctly higher occupancy and vacancy rates for agricultural production than the rocky islands. At the single island scale within the same archipelago, the developments of agricultural production and urban construction distinctly increased with the increase in the island area. The dependency of island constructions on the external world in Dongtou Archipelago was higher than that in Miaodao Archipelago. Meanwhile, the difference in traffic conditions between the two archipelagos did not distinctly influence the food dependency on the external world. Then, practical suggestions in terms of quantity control and quality promotion were proposed to improve the island carrying capacity.
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Background: The accurate detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the key to control Coronavirus Disease-2019 (COVID-19). The performance of different antibody detection methods for diagnosis of COVID-19 is inconclusive. Methods: Between 16 February and 28 February 2020, 384 confirmed COVID-19 patients and 142 healthy controls were recruited. 24 different serological tests, including 4 enzyme-linked immunosorbent assays (EIAs), 10 chemiluminescent immunoassays (CLIAs), and 10 lateral flow immunoassays (LFIAs), were simultaneously performed. Results: The sensitivities of anti-SARS-CoV-2 IgG and IgM antibodies with different reagents ranged from 75 to 95.83% and 46.09 to 92.45%, respectively. The specificities of both anti-SARS-CoV-2 IgG and IgM were relatively high and comparable among different reagents, ranged from 88.03 to 100%. The area under the curves (AUCs) of different tests ranged from 0.733 to 0.984, and the AUCs of EIAs or CLIAs were significantly higher than those of LFIAs. The sensitivities of both IgG and IgM gradually increased with increase of onset time. After 3-4 weeks, the sensitivities of anti-SARS-CoV-2 IgG were maintained at a certain level but the sensitivities of IgM were gradually decreased. Six COVID-19 patients who displayed negative anti-SARS-CoV-2 results were associated with the factors such as older age, having underlying diseases, and using immunosuppressant. Conclusion: Besides the purpose of assessing the impact of the SARS-CoV-2 pandemic in the population, SARS-CoV-2 antibody assays may have an adjunct role in the diagnosis and exclusion of COVID-19, especially by using high-throughput technologies (EIAs or CLIAs).
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BACKGROUND: Targeted therapy has revolutionized the treatment of patients with malignancies harboring mutations in driver genes and has brought a favorable survival benefit to the population with actionable oncogenic mutations. In recent years, the MET exon14 skipping mutation has been recognized as a potentially promising therapeutic target in non-small cell lung cancer (NSCLC). These changes are mutually exclusive with molecular drivers such as EGFR, KRAS, HER-2, BRAF, ALK and ROS1. The prevalence rate of coexisting MET exon 14 mutations and EGFR sensitive mutations (L858R, exon 19 deletions) in Chinese population was reported to be 0.2% (3/1590). However, the coexistence of MET exon 14 mutations with EGFR exon 20 insertion mutations has never been reported and the management of this subtype is not identified. CASE PRESENTATION: A 69-year-old male with a right lung adenocarcinoma (T4N2M0, IIIB) was confirmed to be positive for MET exon 14 skipping (c.3028_3028+1delGGinsTT, 44.4%), MET amplification (copy number 4.4), and EGFR exon 20 insertion (p. N771_H773dup, 22.1%) mutations. After the progression of one cycle of chemotherapy (Pemetrexed 0.8 g d1), the patient was subsequently accepted treatment with Crizotinib (250 mg twice a day) and achieved an important clinical remission for six months until the development of brain metastases. Then, he was submitted to a cycle of anti-programmed cell death-1 (PD-1) therapy after failure of Crizotinib and eventually acquired resistance despite of the high expression of programmed death ligand-1 (PD-L1) and tumor mutational burden (TMB) status. CONCLUSION: This case report provides treatment strategies for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)-untreated lung adenocarcinoma patients simultaneously carrying MET alterations and EGFR exon 20 insertion mutations. In addition, the signatures of PD-L1 or TMB expression were not the candidate for predicting the efficacy of immunotherapy in this context.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Idoso , Quinase do Linfoma Anaplásico/genética , Antígeno B7-H1/genética , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas/genéticaRESUMO
In the current research, two coordination polymers (CPs) have been produced solvothermally on the basis of a semi-rigid multifunctional tricarboxylate, i.e., 5-(3,4-dicarboxylphenoxy) nicotic acid (H3L), and the chemical compositions of the two compounds are [Zn(H2L)2(H2O)2] 1 and [Zn(HL)(2,2'-bpy)] (2, 2,2'-bpy = 2,2'-bipyridine), respectively. The structures and CHN analysis of both complexes were researched. The structural analysis results show that complex 1 features a 2D layered network with sql-type topology and complex 2 demonstrates a 2D layered network with uninodal hcb topology. The therapeutic activity and nursing application values of compounds against coronary heart disease were explored, and their relevant mechanism was assessed in meantime. The endothelin (ET) and prostacyclin (PGI2) contents released by the arterial endothelial cells into plasma were determined with ELISA assay. In addition to this, the alpha granule membrane protein 140 (GMP140) on the platelet was determined with real-time RT-PCR assay.
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Background: With the development of gene-sequencing technology, genome biomarkers, including Erb-B2 receptor tyrosine kinase 2 (ERBB2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (pIK3CA), BReast CAncer gene 1 (BRCA1), and BReast CAncer gene 2 (BRCA2), and immunomarkers, including the tumor mutational burden (TMB) and programmed death-ligand 1 (PD-L1), have become important in the selection of treatment. Methods: Twenty patients with early stage breast cancer who underwent surgery were enrolled in this study. Tissue samples and paired postoperative peripheral blood samples were collected and subjected to the targeted-capture sequencing of 1,021 cancer-associated genes. Results: The most frequently altered genes were tumor protein 53 (TP53; 70%), PIK3CA (40%), protooncogene MYC (35%), ERBB2 (30%), and cyclin-dependent kinase 12 (CDK12; 20%). Six (30%) patients presented with ERBB2 amplification of NGS and simultaneously were positive for human epidermal growth factor receptor 2 (HER2) of IHC. ERBB2 amplification and being HER2 positive were common in breast cancer patients without lymph node metastasis (5/6, 83.3%) and those in stages IA-IIA. Most of the somatic mutations clustered in the TP53 pathway, followed by the PI3K pathway. The TMB was lower than metastatic breast cancer in our cohort, and ranged from 0 to 9.6 mut/Mb (median: 1.92 mut/Mb). Interestingly, more patients had the ERBB2 mutation in the non-lymph node metastasis group than the lymph node metastasis group (55.6% vs. 9.1%; P=0.049). Similarly, more patients had the CDK12 mutation in the non-lymph node metastasis group than the lymph node metastasis group (44.4% vs. 0%; P=0.026). Circulating tumor deoxyribonucleic acid (ctDNA) was detected in 7 of the 20 patients (35%). Of these patients, 71.4% (5/7) were in stage I/II. In addition, no correlation was found between ctDNA detection and clinicopathological features or the driver gene mutations (e.g., PIK3CA and ERBB2). However, patients positive for ctDNA had a higher TMB than those negative for ctDNA when grouped according to the median TMB (1.92 mut/Mb; 85.7% vs. 38.5%; P=0.043). Conclusions: This study described that genomic characteristics of Chinese early stage breast cancer, and the results showed that TMB was related to the detection of ctDNA in postoperative blood.
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Background: This study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM). Methods: Twenty-eight pediatric patients with IM aged 3-8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected. Results: The percentages and absolute numbers of CD3+ and CD8+ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve CD4+ and CD8+ T cells were decreased but with increased percentages of memory CD4+ and CD8+ T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-αß, and inhibitory receptors PD-1, TIGIT in CD8+ T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-γ, IL-2, and TNF-α) secretion capability of CD4+ and CD8+ T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8+ T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8+ T cells was significantly correlated with high viral load and abnormal liver function results. Conclusion: Robust expansion and upregulation of HLA-DR in CD8+ T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8+ T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.
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Linfócitos T CD8-Positivos/metabolismo , Antígenos HLA-DR/biossíntese , Mononucleose Infecciosa/imunologia , Subpopulações de Linfócitos/metabolismo , Subpopulações de Linfócitos B/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Citocinas/metabolismo , Diagnóstico Precoce , Feminino , Regulação da Expressão Gênica/imunologia , Genes MHC da Classe II , Antígenos HLA-DR/genética , Humanos , Memória Imunológica , Imunofenotipagem , Mononucleose Infecciosa/diagnóstico , Ativação Linfocitária , Contagem de Linfócitos , Masculino , Monócitos/imunologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: This study aimed to investigate the efficiency of combining tumor-associated antigens (TAAs) and autoantibodies in the diagnosis of lung cancer. METHODS: The serum levels of TAAs and seven autoantibodies (7-AABs) were detected from patients with lung cancer, benign lung disease and healthy controls. The performance of a new panel by combing TAAs and 7-AABs was evaluated for the early diagnosis of lung cancer. RESULTS: The positive rate of 7-AABs was higher than the single detection of antibody. The positive rate of the combined detection of 7-AABs in lung cancer group (30.2%) was significantly higher than that of healthy controls (16.8%), but had no statistical difference compared with that of benign lung disease group (20.8%). The positive rate of 7-AABs showed a tendency to increase in lung cancer patients with higher tumor-node-metastasis (TNM) stages. For the pathological subtype analysis, the positive rate of 7-AABs was higher in patients with squamous cell carcinoma and small cell lung cancer than that of adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragment 211 (CYFRA 21-1) were significantly higher than that of benign lung disease and healthy control groups. An optimal model was established (including 7-AABs, CEA and CYFRA21-1) to distinguish lung cancer from control groups. The performance of this model was superior than that of single markers, with a sensitivity of 52.26% and specificity of 77.46% in the training group. Further assessment was studied in another validation group, with a sensitivity of 44.02% and specificity of 83%. CONCLUSIONS: The diagnostic performance was enhanced by combining 7-AABs, CEA and CYFRA21-1, which has critical value for the screening and early detection of lung cancer.
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Autoanticorpos/imunologia , Molécula de Adesão da Célula Epitelial/imunologia , Neoplasias Pulmonares/diagnóstico , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Diabetic nephropathy (DN) remains the major cause of end-stage renal disease. MicroRNAs (miRNAs) have been reported to perform biological functions in many diseases. This investigation elucidated the biological role of miR-17-5p in DN. In this study, high glucose-cultured human mesangial cells (HMCs) were used as a cell model of DN. The miR-17-5p and KIF23 expression was measured by RT-qPCR. Cell apoptosis was detected by flow cytometry. The protein levels of apoptosis markers, fibrosis markers, and Wnt/ß-catenin signaling-related genes were assessed using western blotting. The interaction of miR-17-5p with KIF23 was tested by a luciferase reporter assay. We found that miR-17-5p was upregulated in both DN patients and high glucose-treated HMCs. Silencing miR-17-5p attenuated the apoptosis and fibrosis in high glucose-treated HMCs. MiR-17-5p binds to KIF23 3'UTR and negatively regulates KIF23 expression. KIF23 knockdown could suppress the role of miR-17-5p inhibition in high glucose-treated HMCs. Additionally, inhibition of miR-17-5p activated Wnt/ß-catenin signaling in HMCs through upregulating KIF23 expression. Suppression of Wnt/ß-catenin signaling antagonized the effect of miR-17-5p in HMCs. In conclusion, miR-17-5p inhibition alleviates the apoptosis and fibrosis in high glucose-treated HMCs by targeting KIF23 activating Wnt/ß-catenin signaling.
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MicroRNAs , beta Catenina , Apoptose , Proliferação de Células , Regulação para Baixo , Fibrose , Glucose , Humanos , Células Mesangiais/metabolismo , Proteínas Associadas aos Microtúbulos , beta Catenina/metabolismoRESUMO
The present study was designed to fabricate a new chitosan-collagen sponge (CCS) for potential wound dressing applications. CCS was fabricated by a 3.0% chitosan mixture with a 1.0% type I collagen (7:3(w/w)) through freeze-drying. Then the dressing was prepared to evaluate its properties through a series of tests. The new-made dressing demonstrated its safety toward NIH3T3 cells. Furthermore, the CCS showed the significant surround inhibition zone than empty controls inoculated by E. coli and S. aureus. Moreover, the moisture rates of CCS were increased more rapidly than the collagen and blank sponge groups. The results revealed that the CCS had the characteristics of nontoxicity, biocompatibility, good antibacterial activity, and water retention. We used a full-thickness excisional wound healing model to evaluate the in vivo efficacy of the new dressing. The results showed remarkable healing at 14th day post-operation compared with injuries treated with collagen only as a negative control in addition to chitosan only. Our results suggest that the chitosan-collagen wound dressing were identified as a new promising candidate for further wound application.
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Quitosana , Animais , Bandagens , Quitosana/farmacologia , Colágeno , Escherichia coli , Camundongos , Células NIH 3T3 , Staphylococcus aureus , CicatrizaçãoRESUMO
NS gene is generally considered to be related to the virulence of highly pathogenic avian influenza virus (AIV). In recent years, the strains with five amino acids added to the 80-84 positions of the NS1 protein have become prevalent in H5N1 subtype AIVs isolated from mammals. However, the pathogenicity and mechanism of this pattern in mammals remain unclear. In this study, H5N1 subtype AIVs without 80-84 amino acids of the NS1 protein (rNSΔ5aa ) and a mutant virus (rNS5aa-R ) with no deletion of 80-84 amino acids of the NS1 protein were used to determine the pathogenicity in mice. Our results showed that rNS5aa-R possessed an enhanced pathogenicity compared with rNSΔ5aa in vivo and in vitro, which was accompanied by high expression of IL-6, MX1 and CXCL10 in murine lungs. Furthermore, we found that rNS5aa-R increased the infection ability to dendritic cells (DCs). Besides, rNS5aa-R enhanced the expression of phenotypic markers (CD80, CD86, CD40 and MHCII), activation marker CD69, inflammatory cytokines (IL-6, TNF-α and IL-10) and antagonized interferon (IFN-α) of DCs, in comparison to rNSΔ5aa . Moreover, rNS5aa-R induced DCs to quickly migrate into nearby cervical lymph nodes by highly upregulating CCR7, and CD86 showed a high expression on the migrated DCs. We also found that rNS5aa-R -infected DCs significantly promoted the allogeneic CD4+ T-cell proliferation. These findings suggested that rNS5aa-R strongly induced the innate immune response compared with the rNSΔ5aa , which is conducive to activate a wide immune response, resulting in a strong cytokine storm and causing an enhanced pathogenicity of H5N1 subtype AIVs in mammals.
Assuntos
Virus da Influenza A Subtipo H5N1 , Infecções por Orthomyxoviridae , Aminoácidos , Animais , Aves , Células Dendríticas , Humanos , Virus da Influenza A Subtipo H5N1/genética , Mamíferos , Camundongos , Infecções por Orthomyxoviridae/patologia , Proteínas não Estruturais Virais/genética , VirulênciaRESUMO
Global change significantly influences plant leaf gas exchange, which affects the carbon-water cycle of terrestrial ecosystems. However, the magnitudes of the effects of multiple global change factors on leaf gas exchanges are currently lacking. Therefore, a global meta-analysis of 337 published articles was conducted to determine the effects of elevated CO2 (eCO2), elevated O3 (eO3), elevated temperature (eT), and drought on plant leaf gas exchanges. The results indicated that (1) the overall responses of photosynthesis rate (Pn) and instantaneous water use efficiency (WUEi) to eCO2 increased by 28.6% and 58.6%. But transpiration rate (Tr) and stomatal conductance (gs) responded negatively to eCO2 (- 17.5% and - 17.2%, respectively). Furthermore, all Pn, gs, and WUEi responded negatively to eO3 (- 32.7%, - 24.6%, and - 27.1%), eT (- 23.2%, - 10.8%, and - 28.9%), and drought (- 53.6%, - 59.3%, and - 4.6%, respectively), regardless of functional groups and various complex experimental conditions. (2) Elevated CO2 increased WUEi combined with eO3, eT, and drought (26.6%, 36.0%, and 58.6%, respectively, for eCO2 + eO3, eCO2 + eT, and eCO2 + drought) and mitigated their negative impacts on Pn to some extent. (3) Plant form and foliage type play an important role in the responses of leaf gas exchanges. Trees responded mostly to eCO2, but responded least to eT in Pn, Tr, gs, and WUEi compared with shrubs and herbs. Evergreen broad-leaved species were more responsive to eCO2 and drought. (4) The stress level of each factor can also significantly influence the responses of leaf gas exchanges to environment change. Hopefully, the quantitative results are helpful for the further assessments of the terrestrial carbon-water cycle.