RESUMO
Seeking noble-metal-free catalysts for efficient synthesis of aryl nitriles under mild conditions poses a significant challenge due to the use of hypertoxic cyanides or high-pressure/temperature NH3/O2 in conventional synthesis processes. Herein, we developed a novel framework 1 assembled by [Ni72] nanocages with excellent solvents/pH stability. To investigate the structure-activity relationship of catalytic performance, several isostructural MOFs with different molar ratios of Ni/Cu by doping Cu2+ into framework 1 (Ni0.59Cu0.41 (2), Ni0.81Cu0.19 (3), Ni0.88Cu0.12 (4), and Ni0.92Cu0.08 (5)) were prepared. Catalytic studies revealed that catalyst 3 exhibited remarkable performance in the synthesis of aryl nitriles, utilizing a formamide alternative to hypertoxic NaCN/KCN. Notably, catalyst 3 achieved an excellent TOF value of 9.8 h-1. Furthermore, catalyst 3 demonstrated its applicability in a gram-scale experiment and maintained its catalytic performance even after six recycling cycles, owing to its high stability resulting from significant electrostatic and orbital interactions between the Ni center and ligands as well as a large SOMO-LUMO energy gap supported by DFT calculations. Control experiments and DFT calculations further revealed that the excellent catalytic performance of catalyst 3 originated from the synergistic effect of Ni/Cu. Importantly, this work not only provides a highly feasible method to construct highly stable MOFs containing multinuclear nanocages with exceptional catalytic performance but also represents the first example of a heterogeneous catalyst for the synthesis of aryl nitriles using formamide as the cyanide source.
RESUMO
The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.
Assuntos
Ciclo Celular , Dano ao DNA , Estruturas R-Loop , Humanos , Ciclo Celular/genética , Animais , Instabilidade Genômica , Neoplasias/patologia , Neoplasias/metabolismo , Neoplasias/genética , MutaçãoRESUMO
Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the significance of A-to-I editing in disease development, it is important to unravel the complex roles of ADAR1 in cancer for the development of novel therapeutic interventions.In this review, we briefly describe the progress of research on A-to-I editing and ADARs in cancer, mainly focusing on the role of ADAR1 in cancer from both editing-dependent and independent perspectives. In addition, we also summarized the factors affecting the expression and editing activity of ADAR1 in cancer.
Assuntos
Neoplasias , Proteínas de Ligação a RNA , Animais , Humanos , Proteínas de Ligação a RNA/genética , Neoplasias/metabolismo , Adenosina Desaminase/genética , RNA , Mamíferos/metabolismoRESUMO
ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AMLâ cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.
Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/uso terapêutico , Linhagem Celular Tumoral , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Proteólise , Proteína Supressora de Tumor p53/metabolismoRESUMO
Neurodegenerative diseases such as Parkinson's disease (PD) have complex pathogenetic mechanisms. Genetic, age, and environmental factors are all related to PD. Due to the unclear pathogenesis of PD and the lack of effective cure methods, it is urgent to find new targets for treating PD patients. Ferroptosis is a form of cell death that is reliant on iron and exhibits distinct morphological and mechanistic characteristics compared to other types of cell death. It encompasses a range of biological processes, including iron/lipid metabolism and oxidative stress. In recent years, research has found that ferroptosis plays a crucial role in the pathophysiological processes of neurodegenerative diseases and stroke. Therefore, ferroptosis is also closely related to PD, This article reviews the core mechanisms of ferroptosis and elucidates the correlation between PD and ferroptosis. In addition, new compounds that have emerged in recent years to exert anti PD effects by inhibiting the ferroptosis signaling pathway were summarized. I hope to further elaborate the relationship between ferroptosis and PD through the review of this article, and provide new strategies for developing PD treatments targeting ferroptosis.
Assuntos
Ferroptose , Doença de Parkinson , Ferroptose/fisiologia , Humanos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Animais , Ferro/metabolismo , Estresse Oxidativo/fisiologia , Transdução de Sinais/fisiologia , Metabolismo dos Lipídeos/fisiologiaRESUMO
Background and aim: Metabolic-associated fatty liver disease (MAFLD) has gradually become one of the main health concerns regarding liver diseases. Postmenopausal women represent a high-risk group for MAFLD; therefore, it is of great importance to identify and intervene with patients at risk at an early stage. This study established a predictive nomogram model of MAFLD in postmenopausal women and to enhance the clinical utility of the new model, the researchers limited variables to simple clinical and laboratory indicators that are readily obtainable. Methods: Data of 942 postmenopausal women from January 2023 to October 2023 were retrospectively collected and divided into two groups according to the collection time: the training group (676 cases) and the validation group (226 cases). Significant indicators independently related to MAFLD were identified through univariate logistic regression and stepwise regression, and the MAFLD prediction nomogram was established. The C-index and calibration curve were used to quantify the nomogram performance, and the model was evaluated by measuring the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: Of 37 variables, 11 predictors were identified, including occupation (worker), body mass index, waist-to-hip ratio, number of abortions, anxiety, hypertension, hyperlipidemia, diabetes, hyperuricemia, and diet (meat and processed meat). The C-index of the training group predicting the related risk factors was 0.827 (95% confidence interval [CI] 0.794-0.860). The C-index of the validation group was 0.787 (95% CI 0.728-0.846). Calibration curves 1 and 2 (BS1000 times) were close to the diagonal, showing a good agreement between the predicted probability and the actual incidence in the two groups. The AUC of the training group was 0.827, the sensitivity was 0.784, and the specificity was 0.735. The AUC of the validation group was 0.787, the sensitivity was 0.674, and the specificity was 0.772. The DCA curve showed that the nomogram had a good net benefit in predicting MAFLD in postmenopausal women. Conclusions: A predictive nomogram for MAFLD in postmenopausal women was established and verified, which can assist clinicians in evaluating the risk of MAFLD at an early stage.
Assuntos
Nomogramas , Pós-Menopausa , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Medição de Risco/métodos , Curva ROCRESUMO
Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.
RESUMO
Dihydroartemisinin (DHA), a derivative of artemisinin which is primarily used to treat malaria in clinic, also confers protective effect on lipopolysaccharide-induced nephrotoxicity. While, the activities of DHA in cisplatin (CDDP)-caused nephrotoxicity are elusive. To investigate the role and underlying mechanism of DHA in CDDP-induced nephrotoxicity. Mice were randomly separated into four groups: normal, CDDP, and DHA (25 and 50 mg/kg were orally injected 1 h before CDDP for consecutive 10 days). All mice except the normal were single injected intraperitoneally with CDDP (22 mg/kg) for once on the 7th day. Combined with quantitative proteomics and bioinformatics analysis, the impact of DHA on renal cell apoptosis, oxidative stress, biochemical indexes, and inflammation in mice were investigated. Moreover, a human hepatocellular carcinoma cells xenograft model was established to elucidate the impact of DHA on tumor-related effects of CDDP. DHA reduced the levels of creatinine (CREA) (p < 0.01) and blood urea nitrogen (BUN) (p < 0.01), reversed CDDP-induced oxidative, inflammatory, and apoptosis indexes (p < 0.01). Mechanistically, DHA attenuated CDDP-induced inflammation by inhibiting nuclear factor κB p65 (NFκB p65) expression, and suppressed CDDP-induced renal cell apoptosis by inhibiting p63-mediated endogenous and exogenous apoptosis pathways. Additionally, DHA alone significantly decreased the tumor weight and did not destroy the antitumor effect of CDDP, and did not impact AST and ALT. In conclusion, DHA prevents CDDP-triggered nephrotoxicity via reducing inflammation, oxidative stress, and apoptosis. The mechanisms refer to inhibiting NFκB p65-regulated inflammation and alleviating p63-mediated mitochondrial endogenous and Fas death receptor exogenous apoptosis pathway.
Assuntos
Antineoplásicos , Artemisininas , Humanos , Camundongos , Animais , Cisplatino/toxicidade , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Artemisininas/metabolismo , Rim/metabolismo , Rim/patologia , Estresse Oxidativo , Inflamação/metabolismo , Apoptose , Antineoplásicos/toxicidadeRESUMO
The energy oriented mine ecological restoration mode of photovoltaic+ecological restoration provides a breakthrough for alleviating the dilemma of photovoltaic land development and solving the urgent need for restoration of abandoned mining land. Taking a mining area in central Liaoning Province as an example, we established three photovoltaic+mining ecological restoration modes, including forest-photovoltaic complementary, agriculture-photovoltaic, and grass photovoltaic complementation. Combined with the life cycle assessment method, we calculated and assessed the potential of photovoltaic+mining ecological restoration in carbon reduction and sink enhancement. The average annual carbon reduction and sink increase was 514.93 t CO2·hm-2 under the photovoltaic+mining ecological restoration mode, while the average annual carbon reduction per megawatt photovoltaic power station was 1242.94 t CO2. The adoption of photovoltaic+ecological restoration mode in this mining area could make carbon reduction and sink enhancement 6.30-7.79 Mt CO2 during 25 years. The carbon reduction and sink increment mainly stemmed from the photovoltaic clean power generation induced carbon reduction, accounting for 96.4%-99.4%, while the contribution of ecosystem carbon sink increment was small, accounting for only 0.6%-3.7% of the total. Among different photovoltaic+ecological restoration modes, the carbon reduction and sink increment was the largest in forest-photovoltaic complementary (7.11 Mt CO2), followed by agriculture-photovoltaic (7.04 Mt CO2), and the least in grass photovoltaic complementation (6.98 Mt CO2). Constructing the development mode of "photovoltaic+mining ecological restoration" could effectively leverage the dual benefits of reducing emissions from photovoltaic power generation and increase sinks from mining ecological restoration, which would be helpful for achieving the goal of carbon neutrality in China.
Assuntos
Sequestro de Carbono , Ecossistema , Mineração , China , Recuperação e Remediação Ambiental/métodos , Modelos Teóricos , Carbono/química , Carbono/análise , Conservação dos Recursos Naturais/métodos , Dióxido de Carbono/análise , Energia SolarRESUMO
The flexible and self-healing supercapacitors (SCs) are considered to be promising smart energy storage devices. Nevertheless, the SCs integrated with flexibility, lightweight, pattern editability, self-healing capabilities and desirable electrochemical properties remain a challenge. Herein, an all-in-one self-healing SC fabricated with the free-standing hybrid film (TCMP) composed of the 2,2,6,6-tetramethylpiperidin-1-yloxy-oxidized cellulose nanofibers (TOCNs) carried carbon nanotubes (CNTs), manganese dioxide (MnO2) and polyaniline (PANI) as the electrode, polyvinyl alcohol/sulfuric acid (PVA/H2SO4) gel as the electrolyte and dynamically cross-linked cellulose nanofibers/PVA/sodium tetraborate decahydrate (CNF/PB) hydrogel as the self-healing electrode matrix is developed. The TCMP film electrodes are fabricated through a facile in-situ polymerization of MnO2 and PANI in TOCNs-dispersed CNTs composite networks, exhibiting lightweight, high electrical conductivity, flexibility, pattern editability and excellent electrochemical properties. Benefited from the hierarchically porous structure and high mechanical properties of TOCNs, excellent electrical conductivity of CNTs and the desirable synergistic effect of pseudocapacitance induced by MnO2 and PANI, the assembled SC with an interdigital structure demonstrated a high areal capacitance of 1108 mF cm-2 at 2 mA cm-2, large areal energy density of 153.7 µWh cm-2 at 1101.7 µW cm-2. A satisfactory bending cycle performance (capacitance retention up to 95 % after 200 bending deformations) and self-healing characteristics (â¼90 % capacitance retention after 10 cut/repair cycles) are demonstrated for the TCMP-based symmetric SC, delivering a feasible strategy for electrochemical energy storage devices with excellent performance, designable patterns and desirable safe lifespan.
RESUMO
Carbon capture and storage (CCS) technology is an important way to slow down the continuous increase in atmospheric CO2 concentration and to achieve the dual carbon target. Carbon capture and storage through biomass ash is a secure, permanent, and environment friendly way. To better understand the characteristics of biomass ash carbon capture and storage, we summarized progresses on biomass ash carbon capture and storage, clarified the mechanisms of biomass ash carbon sequestration, analyzed the influencing factors, and explored its applications in various domains. The capacity of CCS by biomass ash mainly derived from alkaline earth metal oxides of CaO and MgO. The actual carbon sequestration efficiency is affected by factors such as biomass source, chemical composition, temperature, humidity, pressure, and CO2 concentration. However, the underlying mechanism is unclear. The CCS capacity of biomass ash significantly impacts its potential applications in building materials reuse, soil quality improvement, and adsorbents carbon capture and storage absorbent preparation. Long-term research is critically needed. For future studies, we should strengthen the research on the carbonization efficiency of biomass ash from multiple sources, establish a database related to the impact of biomass ash carbonization, build a methodological system to promote scientific management of biomass ash, develop biomass ash carbon capture and storage technologies, and quantitatively assess its role in carbon sequestration.
Assuntos
Dióxido de Carbono , Carbono , Dióxido de Carbono/química , Biomassa , Óxidos , Temperatura , Sequestro de CarbonoRESUMO
Objective To investigate the effects and mechanisms of TAR DNA-binding protein 43(TDP-43)on oxygen-glucose deprivation(OGD)-induced apoptosis in mouse atrial myocytes(HL-1 cells).Methods The in vitro cultured mouse atrial myocytes(HL-1 cells)were divided into:(1)control group and groups with different OGD treatment times(2,4,8,16 h),and cell viability was detected by CCK-8 assay,and TDP-43 protein expression level was detected by Western blotting,which was used to determine the time point of OGD induction for the subsequent study;(2)control and OGD groups,flow cytometry was used to detect apoptosis,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect adenosine triphosphate(ATP)relative content,microplate method to detect malondialdehyde(MDA)content,and WST-1 method to detect superoxide dismutase(SOD)content.Mouse atrial myocytes(HL-1 cells)transfected with lentivirus were divided into:(1)negative control lentiviral intervention group(NC-shRNA),TDP-43 knockdown lentiviral intervention group(TDP-43-shRNA1,TDP-43-shRNA2,TDP-43-shRNA3),and Western blotting was used to detect the TDP-43 protein expression level,and the group with the highest lentiviral knockdown efficiency was selected as the TDP-43-shRNA for subsequent experiments;(2)NC-shRNA group,TDP-43-shRNA group,OGD+NC-shRNA group,OGD+TDP-43-shRNA group,under normoxic and OGD conditions,flow cytometry was used to detect the apoptosis rate,MitoTracker staining to detect mitochondrial morphology,JC-1 staining to detect mitochondrial membrane potential,chemiluminescence to detect the relative content of ATP,flow cytometry to detect the fluorescence intensity of reactive oxygen species(ROS),microplate to detect the content of MDA,and WST-1 to detect the content of SOD.Results CCK-8 method showed that,with the prolongation of OGD time,the viability of mouse atrial myocytes(HL-1 cells)gradually decreased;Western blotting assay showed that the expression level of TDP-43 protein gradually increased,and both of them showed a strong time-dependence.Compared with control group,mouse atrial myocytes(HL-1 cells)viability was the lowest(P<0.05)and TDP-43 protein expression was the highest(P<0.05)at 16 h of OGD,accordingly,OGD 16 h was chosen as the induction time point for subsequent experiments.Compared with control group,the apoptosis rate,the fluorescence intensity ratio of mitochondrial membrane potential and the content of MDA increased,the relative content of ATP and SOD decreased in OGD group,and the differences were all statistically significant(P<0.05).Western blotting detection showed that compared with NC-shRNA group,the TDP-43-shRNA2 group had the most obvious reduction in TDP-43 protein expression level(P<0.05)and the highest knockdown efficiency,so the TDP-43-shRNA2 group was selected for subsequent experiments.The results of flow cytometry showed that under normoxic conditions,there was no significant change in the apoptosis rate in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);and under OGD conditions,the apoptosis rate in OGD+TDP-43-shRNA group reduced when compared with OGD+NC-shRNA group(P<0.05).MitoTracker staining results showed that the mitochondrial morphology of TDP-43-shRNA group was intact without significant changes compared with NC-shRNA group;the mitochondria of OGD+NC-shRNA group increased in number,most of which were fragmented and scattered in distribution;compared with OGD+NC-shRNA group,the mitochondrial morphology of OGD+TDP-43-shRNA group was restored.Under normoxic conditions,there were no significant changes in mitochondrial membrane potential,relative ATP content,ROS fluorescence intensity,MDA content,and SOD content in TDP-43-shRNA group compared with NC-shRNA group(P>0.05);however,under OGD conditions,the ratio of fluorescence intensity of mitochondrial membrane potential of cells the fluorescence intensity of ROS,and the content of MDA decreased,and the relative content of ATP and the content of SOD increased in OGD+TDP-43-shRNA group compared with that of OGD+NC-shRNA group,and all of these differences was statistically significant(P<0.05).Conclusion TDP-43 exacerbates OGD-induced mitochondrial dysfunction by regulating cardiomyocyte apoptosis;therefore,knockdown of TDP-43 expression is expected to be a potential therapeutic strategy for ischemic cardiomyopathy.
RESUMO
Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20+B cells, CD4+T cells, and FOXP3+Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20+B cells, CD4+T cells and FOXP3+Treg cells in LELC may suggest a better prognosis.
Assuntos
Humanos , Linfócitos do Interstício Tumoral , Herpesvirus Humano 4 , Relevância Clínica , Prognóstico , Carcinoma de Células Escamosas/patologia , Fatores de Transcrição ForkheadRESUMO
Objective: To assess the clinical features and treatment outcomes in patients with primary ovarian squamous cell carcinoma (POSCC). Methods: Fifteen patients with primary ovarian squamous cell carcinoma diagnosed from January 2009 to December 2018 in Cancer Hospital of the University of Chinese Academy of Sciences were collected. The expression of p16, hMLH1, hMSH2, hMSH6 and PMS2 in POSCC was detected by immunohistochemistry, and the status of high-risk human papillomavirus (HPV) by RNAscope test. Results: Squamous cell carcinoma with different degrees of differentiation was found in 15 cases, including three cases with high differentiation and 12 cases with medium to low differentiation. There were four cases with in situ squamous cell carcinoma, four cases with teratoma, one case with endometrial carcinoma/atypical hyperplasia, and one case with endometriosis. p16 was expressed in five cases (5/15), indicating coexisting high-risk HPV infection. There was no high-risk HPV infection in the remaining 10 cases, and p16 staining was negative. There was no deficient mismatch repair protein in all cases. The overall survival time (P=0.038) and progression free survival (P=0.045) of patients with high-risk HPV infection were longer than those without HPV infection. Conclusions: POSCC is more commonly noted in postmenopausal women and often occurs unilaterally. Elevated serological indexes CA125 and SCC are the most common finding. Morphologically, the tumors show variable degrees of differentiation, but the current data suggest that the degree of differentiation cannot be used as an independent prognostic index. High-risk HPV infection may be associated with the occurrence of POSCC, and that the prognosis of POSCC patients with HPV infection is better than that of patients without infection.
Assuntos
Feminino , Humanos , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Imuno-Histoquímica , Infecções por Papillomavirus/diagnóstico , PrognósticoRESUMO
BACKGROUND: Application of neural stem cells (NSCs) is of great current interest in neuroscience, but NSCs origin is very limited. And they always differentiate into a large percentage of glial cells and small percentage of neurons in natural differentiation process, so researchers should take effective measures to promote NSCs differentiation into certain offsprings. Previous studies have shown that ginseng saponin ingredients, such as Rb1 and Rg1, have certain influence on NSCs differentiation, but it is unclear whether Rg3 plays a role on NSCs differentiation. OBJECTIVE:To preliminarily investigate the effect of ginsenoside Rg3 on mouse NSCs differentiation into neurons and astrocytes in vitro. METHODS: The fetal cortices of embryonic 14 days (E14) C57BL/6 mice were isolated for culturing primary NSCs. Then passaged NSCs were identified by their purity with NSCs specific antibodies, Nestin and Sox2, by immunofluorescence staining. NSCs were induced for 3 days in the differentiation medium containing ginsenoside Rg3 of different concentrations (blank control, 50 and 250 nmol/L). After that, immunofluorescence staining was used to identify differentiated neurons with neuronal specific antibody, Tuj1, and differentiated astrocytes with astrocyte specific antibody, GFAP. Then, we calculated and statistically analyzed Tuj1+/DAPI and GFAP+/DAPI percentages in the three different groups. Besides, real-time PCR assay was used to test Tuj1 and GFAP mRNA expression in the three groups after 3 days of differentiation. RESULTS AND CONCLUSION: Primary and passaged NSCs were successfully cultured and almost of cells were positive for both Nestin and Sox2, so these high-purity NSCs could be used in the following experiments. Immunofluorescence staining and statistical analysis results showed that compared with the blank control and 250 nmol/L groups, 50 nmol/L group had an obviously increased neuronal percentage after 3 days differentiation (P < 0.01), while the blank control and 250 nmol/L groups had no significant difference (P > 0.05); compared with the blank control group, 50 and 250 nmol/L groups had significantly increased astrocyte percentages (P < 0.05), whereas there was no obvious difference between 50 and 250 nmol/L groups (P > 0.05). The results of real-time PCR assay were similar with the above immunofluorescence results. In conclusion, 50 nmol/L ginsenoside Rg3 can enhance mouse NSCs differentiation into neurons and astrocytes, while 250 nmol/L ginsenoside Rg3 can only promote mouse NSCs differentiation into astrocytes.
RESUMO
Objective To analyze the results of 3 investigations(2002-2004,2008-2009,and 2016)of major parasitic dis-eases in Shixing County,so as to provide the evidence for formulating further control strategies. Methods With the stratified clus-ter sampling method,5 administrative villages were investigated. A total of 200 residents aged above 3 years were sampled in each village to investigate the eggs of soil-transmitted nematodes with Kato-Katz technique,and the swab method was applied for detecting the eggs of Enterobius vermicularis in children aged 3-9 years. χ2 test was used for statistical analysis. Results To-tally 3857 individuals were surveyed for intestinal parasites,and 5 species of parasites were found and the total infection rates were 28.37%,4.32%and 0.50%in the 3 investigations respectively,and there were statistically significant differences between any two investigations(χ2=287.64,327.60 and 31.89 respectively,and all P<0.01). The infection rates of Ascaris lumbricoi-des,hookworm,Trichuris trichiura and Clonorchis sinensis significantly decreased in the third investigation compared with those in the first investigation(χ2 =424.55,55.45,43.40 and 26.12 respectively,all P<0.01). However,there was no significant difference between the E. vermicularis infection rates of the first investigation and the third investigation(χ2=0.16,P>0.05). Conclusions Compared with the status in the first investigation,the infection rates of A. lumbricoides,hookworm,T. trichiura and C. sinensis are significantly decreased by 90%or more in the third investigation. However,the children's infection rate of E. vermicularis is still very high. Therefore,we should focus on the comprehensive control measures of E. vermicularis infection while formulating further control strategies of parasitic diseases.
RESUMO
Objective To investigate the influence of three extracellular matrix (ECM) proteins, namely, laminin (LN), collagen type I (Col I), fibronectin (FN) on the morphology and contractility changes in airway smooth muscle cells (ASMCs) induced by platelet-derived growth factor-BB (PDGF-BB). Methods ASMCs were seeded on the culture dish coated with LN, Col I, or FN, respectively, and divided into two groups to be cultured either in the absence or presence of PDGF-BB (10 mg/L) for 0~5 d. Subsequently, cell morphology was examined by the optical microscopy and quantified as the ratio of cell width to length, and the KCl/histamine-induced contractile responses of the cell were measured by optical magnetic twisting cytometry (OMTC). Results ASMCs cultured in the presence of PDGF-BB generally appeared in longer and thinner cell shapes, namely, a smaller ratio of cell width to length, but the cell width/length ratio for ASMCs adhered on LN was relatively bigger than that on Col I or FN. In the absence of PDGF-BB, contractility of ASMCs to KCl increased with the duration of culture, which was independent of the ECM proteins. In contrast, in the presence of PDGF-BB, contractility of ASMCs to KCl or histamine decreased in all situations, but degree of the decrease was smaller for ASMCs adhered on LN than those on Col I or FN. Conclusions The morphology and contractility changes in ASMCs induced by PDGF-BB are influenced by ECM proteins on which cells are grown. For ASMCs adhered on LN, the morphology and contractility changes are relatively smaller than those on Col I and FN. The differential effect of ECM proteins on PDGF-BB induced changes in morphology and contractility of ASMCs is important to fully understand the interactions between ECM proteins, inflammatory factors, ASMCs, and their relation to the pathophysiological mechanism of asthma.