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1.
Blood ; 141(7): 766-786, 2023 02 16.
Article in English | MEDLINE | ID: mdl-36322939

ABSTRACT

Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.


Subject(s)
Complement C1q , Leukemia, Myeloid, Acute , Humans , Proteomics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Bone Marrow/metabolism , Prognosis , Chronic Disease , Recurrence
2.
Small ; : e2404092, 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39036856

ABSTRACT

Acidic water electrolysis is of considerable interest due to its higher current density operation and energy conversion efficiency, but its real industrial application is highly limited by the shortage of efficient, stable, and cost-effective acidic oxygen evolution reaction (OER) electrocatalysts. Here, an electrocatalyst consisting of Ni-implanted RuO2 supported is reported on α-MnO2 (MnO2/RuO2-Ni) that shows high activity and remarkable durability in acidic OER. Precisely, the MnO2/RuO2-Ni catalyst shows an overpotential of 198 mV at a current density of 10 mA cm-2 and can operate continuously and stably for 400 h (j = 10 mA cm-2) without any obvious attenuation of activity, making it one of the best-performing acid-stable OER catalysts. Experimental results, in conjunction with density functional theory calculations, demonstrate that the interface electron transfer effect from RuO2 to MnO2, further enhanced by Ni incorporation, effectively modulates the adsorption of OOH* and significantly reduces the overpotential, thereby enhancing catalytic activity and durability.

3.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Article in English | MEDLINE | ID: mdl-34078666

ABSTRACT

Intrinsic mechanisms such as temporal series of transcription factors orchestrate neurogenesis from a limited number of neural progenitors in the brain. Extrinsic regulations, however, remain largely unexplored. Here we describe a two-step glia-derived signal that regulates neurogenesis in the Drosophila mushroom body (MB). In a temporal manner, glial-specific ubiquitin ligase dSmurf activates non-cell-autonomous Hedgehog signaling propagation by targeting the receptor Patched to suppress and promote the exit of MB neuroblast (NB) proliferation, thereby specifying the correct α/ß cell number without affecting differentiation. Independent of NB proliferation, dSmurf also stabilizes the expression of the cell-adhesion molecule Fasciclin II (FasII) via its WW domains and regulates FasII homophilic interaction between glia and MB axons to refine α/ß-lobe integrity. Our findings provide insights into how extrinsic glia-to-neuron communication coordinates with NB proliferation capacity to regulate MB neurogenesis; glial proteostasis is likely a generalized mechanism in orchestrating neurogenesis.


Subject(s)
Cell Communication , Cell Proliferation , Mushroom Bodies/embryology , Neurogenesis , Neuroglia/metabolism , Animals , Drosophila Proteins/metabolism , Drosophila melanogaster
4.
Funct Integr Genomics ; 23(2): 142, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37121989

ABSTRACT

The soil-borne pathogen Verticillium dahliae, also referred as "The Cotton Cancer," is responsible for causing Verticillium wilt in cotton crops, a destructive disease with a global impact. To infect cotton plants, the pathogen employs multiple virulence mechanisms such as releasing enzymes that degrade cell walls, activating genes that contribute to virulence, and using protein effectors. Conversely, cotton plants have developed numerous defense mechanisms to combat the impact of V. dahliae. These include strengthening the cell wall by producing lignin and depositing callose, discharging reactive oxygen species, and amassing hormones related to defense. Despite the efforts to develop resistant cultivars, there is still no permanent solution to Verticillium wilt due to a limited understanding of the underlying molecular mechanisms that drive both resistance and pathogenesis is currently prevalent. To address this challenge, cutting-edge technologies such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), host-induced gene silencing (HIGS), and gene delivery via nano-carriers could be employed as effective alternatives to control the disease. This article intends to present an overview of V. dahliae virulence mechanisms and discuss the different cotton defense mechanisms against Verticillium wilt, including morphophysiological and biochemical responses and signaling pathways including jasmonic acid (JA), salicylic acid (SA), ethylene (ET), and strigolactones (SLs). Additionally, the article highlights the significance of microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) in gene expression regulation, as well as the different methods employed to identify and functionally validate genes to achieve resistance against this disease. Gaining a more profound understanding of these mechanisms could potentially result in the creation of more efficient strategies for combating Verticillium wilt in cotton crops.


Subject(s)
Ascomycota , Neoplasms , Verticillium , Gossypium/genetics , Disease Resistance/genetics , Gene Expression Regulation, Plant , Verticillium/metabolism , Ascomycota/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Diseases/genetics
5.
BMC Plant Biol ; 23(1): 501, 2023 Oct 18.
Article in English | MEDLINE | ID: mdl-37848871

ABSTRACT

BACKGROUND: The cotton industry suffers significant yield losses annually due to Verticillium wilt, which is considered the most destructive disease affecting the crop. However, the precise mechanisms behind this disease in cotton remain largely unexplored. METHODS: Our approach involved utilizing transcriptome data from G. australe which was exposed to Verticillium dahliae infection. From this data, we identified ethylene-responsive factors and further investigated their potential role in resistance through functional validations via Virus-induced gene silencing (VIGS) in cotton and overexpression in Arabidopsis. RESULTS: A total of 23 ethylene response factors (ERFs) were identified and their expression was analyzed at different time intervals (24 h, 48 h, and 72 h post-inoculation). Among them, GauERF105 was selected based on qRT-PCR expression analysis for further investigation. To demonstrate the significance of GauERF105, VIGS was utilized, revealing that suppressing GauERF105 leads to more severe infections in cotton plants compared to the wild-type. Additionally, the silenced plants exhibited reduced lignin deposition in the stems compared to the WT plants, indicating that the silencing of GauERF105 also impacts lignin content. The overexpression of GauERF105 in Arabidopsis confirmed its pivotal role in conferring resistance against Verticillium dahliae infection. Our results suggest that WT possesses higher levels of the oxidative stress markers MDA and H2O2 as compared to the overexpressed lines. In contrast, the activities of the antioxidant enzymes SOD and POD were higher in the overexpressed lines compared to the WT. Furthermore, DAB and trypan staining of the overexpressed lines suggested a greater impact of the disease in the wild-type compared to the transgenic lines. CONCLUSIONS: Our findings provide confirmation that GauERF105 is a crucial candidate in the defense mechanism of cotton against Verticillium dahliae invasion, and plays a pivotal role in this process. These results have the potential to facilitate the development of germplasm resistance in cotton.


Subject(s)
Arabidopsis , Ascomycota , Verticillium , Gossypium/genetics , Gossypium/metabolism , Arabidopsis/genetics , Lignin/metabolism , Hydrogen Peroxide/metabolism , Verticillium/physiology , Ascomycota/metabolism , Ethylenes , Disease Resistance/genetics , Plant Diseases/genetics , Gene Expression Regulation, Plant , Plant Proteins/metabolism
6.
J Transl Med ; 21(1): 871, 2023 11 30.
Article in English | MEDLINE | ID: mdl-38037058

ABSTRACT

BACKGROUND: Tumor cells with stemness in breast cancer might facilitate the immune microenvironment's suppression process and led to anti-tumor immune effects. The primary objective of this study was to identify potential targets to disrupt the communication between cancer cell stemness and the immune microenvironment. METHODS: In this study, we initially isolated tumor cells with varying degrees of stemness using a spheroid formation assay. Subsequently, we employed RNA-seq and proteomic analyses to identify genes associated with stemness through gene trend analysis. These stemness-related genes were then subjected to pan-cancer analysis to elucidate their functional roles in a broader spectrum of cancer types. RNA-seq data of 3132 patients with breast cancer with clinical data were obtained from public databases. Using the identified stemness genes, we constructed two distinct stemness subtypes, denoted as C1 and C2. We subsequently conducted a comprehensive analysis of the differences between these subtypes using pathway enrichment methodology and immune infiltration algorithms. Furthermore, we identified key immune-related stemness genes by employing lasso regression analysis and a Cox survival regression model. We conducted in vitro experiments to ascertain the regulatory impact of the key gene on cell stemness. Additionally, we utilized immune infiltration analysis and pan-cancer analysis to delineate the functions attributed to this key gene. Lastly, single-cell RNA sequencing (scRNA-seq) was employed to conduct a more comprehensive examination of the key gene's role within the microenvironment. RESULTS: In our study, we initially identified a set of 65 stemness-related genes in breast cancer cells displaying varying stemness capabilities. Subsequently, through survival analysis, we pinpointed 41 of these stemness genes that held prognostic significance. We observed that the C2 subtype exhibited a higher stemness capacity compared to the C1 subtype and displayed a more aggressive malignancy profile. Further analysis using Lasso-Cox algorithm identified LDLR as a pivotal immune-related stemness gene. It became evident that LDLR played a crucial role in shaping the immune microenvironment. In vitro experiments demonstrated that LDLR regulated the cell stemness of breast cancer. Immune infiltration analysis and pan-cancer analysis determined that LDLR inhibited the proliferation of immune cells and might promote tumor cell progression. Lastly, in our scRNA-seq analysis, we discovered that LDLR exhibited associations with stemness marker genes within breast cancer tissues. Moreover, LDLR demonstrated higher expression levels in tumor cells compared to immune cells, further emphasizing its relevance in the context of breast cancer. CONCLUSION: LDLR is an important immune stemness gene that regulates cell stemness and enhances the crosstalk between breast cancer cancer cell stemness and tumor immune microenvironment.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/genetics , Multiomics , Proteomics , Algorithms , Lipoproteins, LDL , Tumor Microenvironment
7.
Physiol Plant ; 175(6): e14113, 2023.
Article in English | MEDLINE | ID: mdl-38148227

ABSTRACT

Plant Carbonic anhydrases (Cas) have been shown to be stress-responsive enzymes that may play a role in adapting to adverse conditions. Cotton is a significant economic crop in China, with upland cotton (Gossypium hirsutum) being the most widely cultivated species. We conducted genome-wide identification of the ßCA gene in six cotton species and preliminary analysis of the ßCA gene in upland cotton. In total, 73 ßCA genes from six cotton species were identified, with phylogenetic analysis dividing them into five subgroups. GHßCA proteins were predominantly localized in the chloroplast and cytoplasm. The genes exhibited conserved motifs, with motifs 1, 2, and 3 being prominent. GHßCA genes were unevenly distributed across chromosomes and were associated with stress-responsive cis-regulatory elements, including those responding to light, MeJA, salicylic acid, abscisic acid, cell cycle regulation, and defence/stress. Expression analysis indicated that GHßCA6, GHßCA7, GHßCA10, GHßCA15, and GHßCA16 were highly expressed under various abiotic stress conditions, whereas GHßCA3, GHßCA9, GHßCA10, and GHßCA18 had higher expression patterns under Verticillium dahliae infection at different time intervals. In Gossypium thurberi, GthßCA1, GthßCA2, and GthßCA4 showed elevated expression across stress conditions and tissues. Silencing GHßCA10 through VIGS increased Verticillium wilt severity and reduced lignin deposition compared to non-silenced plants. GHßCA10 is crucial for cotton's defense against Verticillium dahliae. Further research is needed to understand the underlying mechanisms and develop strategies to enhance resistance against Verticillium wilt.


Subject(s)
Ascomycota , Resilience, Psychological , Verticillium , Gossypium/genetics , Gossypium/metabolism , Phylogeny , Verticillium/metabolism , Disease Resistance/genetics , Gene Expression Regulation, Plant , Plant Diseases/genetics , Plant Proteins/genetics , Plant Proteins/metabolism
8.
BMC Biotechnol ; 22(1): 11, 2022 03 20.
Article in English | MEDLINE | ID: mdl-35307009

ABSTRACT

BACKGROUND: Feathers are the most abundant agricultural waste produced by poultry farms. The accumulation of a large number of feathers not only seriously pollutes the environment but also causes the waste of protein resources. The degradation of feather waste by keratinase-producing strains is currently a promising method. Therefore, screening high-producing keratinase strains from marine environment and studying the fermentation conditions, enzymatic properties and feather degradation mechanism are crucial for efficient degradation of feathers. RESULTS: A novel efficient feather-degrading bacteria, Gxun-17, isolated from the soil sample of a marine duck farm of Beibu Gulf in Guangxi, China, was identified as Bacillus tropicus. The optimum fermentation conditions were obtained by single factor and orthogonal tests as follows: feather concentration of 15 g/L, maltose concentration of 10.0 g/L, MgSO4 concentration of 0.1 g/L, initial pH of 7.0 and temperature of 32.5 °C. The strain completely degraded the feathers within 48 h, and the highest keratinase activity was 112.57 U/mL, which was 3.18-fold that obtained with the basic medium (35.37 U/mL). Detecting the keratinase activity and the content of sulphur-containing compounds in the fermentation products showed that the degradation of feathers by the strain might be a synergistic effect of the enzyme and sulphite. The keratinase showed optimal enzyme activity at pH 7.0 and temperature of 60 °C. The keratinase had the best performance on the casein substrate. When casein was used as the substrate, the Km and Vmax values were 15.24 mg/mL and 0.01 mg/(mL·min), respectively. Mg2+, Ca2+, K+, Co2+, Al3+, phenylmethylsulphonyl fluoride and isopropanol inhibited keratinase activity, which indicated that it was a serine keratinase. Conversely, the keratinase activity strongly increased with the addition of Mn2+ and ß-mercaptoethanol. CONCLUSIONS: A novel feather-degrading B. tropicus Gxun-17 was obtained from marine environment. The strain adapted the extreme conditions such as low temperature, high salt and high pressure. Thus, the keratinase had high activity, wide range of temperature and pH, salt tolerance and other characteristics, which had potential application value.


Subject(s)
Caseins , Feathers , Animals , Bacillus , Caseins/metabolism , Chickens/metabolism , China , Feathers/chemistry , Hydrogen-Ion Concentration , Keratins/analysis , Keratins/chemistry , Keratins/metabolism , Peptide Hydrolases/metabolism , Temperature
9.
Ecotoxicol Environ Saf ; 241: 113791, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35753272

ABSTRACT

Sodium propionate is widely used as a preservative in food. The widespread use of preservatives is known to cause both environmental and public health problems. This study aimed to investigate the effects of sodium propionate on the developmental behavior and glucose metabolism of zebrafish. Our results showed that sodium propionate had no significant effect on the embryonic morphological development of zebrafish embryos but changed the head eye area. Then we found sodium propionate disturbed the thigmotaxis behavior, impaired neural development. Moreover, changes in clock gene expression disrupted the circadian rhythm of zebrafish. Circadian genes regulated insulin sensitivity and secretion in various tissues. Then our results showed that the disorder of circadian rhythm in zebrafish affected glucose metabolism and insulin resistance, which damaged the development of retina. Therefore, the safety of propionate should be further evaluated.


Subject(s)
Insulin Resistance , Zebrafish , Animals , Circadian Rhythm , Glucose/metabolism , Propionates/toxicity , Zebrafish/metabolism , Zebrafish Proteins/metabolism
10.
Int J Mol Sci ; 23(15)2022 Jul 29.
Article in English | MEDLINE | ID: mdl-35955574

ABSTRACT

6-BA is a common plant growth regulator, but its safety has not been conclusive. The heart is one of the most important organs of living organisms, and the cardiogenesis process of zebrafish is similar to that of humans. Therefore, based on wild-type and transgenic zebrafish, we explored the development of zebrafish heart under 6-BA exposure and its mechanism. We found that 6-BA affected larval cardiogenesis, inducing defective expression of key genes for cardiac development (myl7, vmhc, and myh6) and AVC differentiation (bmp4, tbx2b, and notch1b), ultimately leading to weakened cardiac function (heart rate, diastolic speed, systolic speed). Acridine orange staining showed that the degree of apoptosis in zebrafish hearts was significantly increased under 6-BA, and the expression of cell-cycle-related genes was also changed. In addition, HPA axis assays revealed abnormally expressed mRNA levels of genes and significantly increased cortisol contents, which was also consistent with the observed anxiety behavior in zebrafish at 3 dpf. Transcriptional abnormalities of pro- and anti-inflammatory factors in immune signaling pathways were also detected in qPCR experiments. Collectively, we found that 6-BA induced cardiotoxicity in zebrafish, which may be related to altered HPA axis activity and the onset of inflammatory responses under 6-BA treatment.


Subject(s)
Cardiotoxicity , Zebrafish , Animals , Benzyl Compounds , Cardiotoxicity/etiology , Cardiotoxicity/metabolism , Embryo, Nonmammalian/metabolism , Humans , Hypothalamo-Hypophyseal System/metabolism , Pituitary-Adrenal System/metabolism , Purines , Zebrafish/metabolism , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism
11.
Ecotoxicol Environ Saf ; 223: 112555, 2021 Oct 15.
Article in English | MEDLINE | ID: mdl-34332249

ABSTRACT

As a highly effective plant hormone, the overuse of 6-benzylaminopurine (6-BA) may pose potential threats to organisms and the environment. Melatonin is widely known for its regulation of sleep rhythm, and it also shows a beneficial effect in a variety of adverse situations. In order to investigate the harm of 6-BA to vertebrates and whether melatonin can reverse the toxicity induced by 6-BA, we analyzed the circadian rhythm and cardiovascular system of zebrafish, and further clarified the role of the thyroid endocrine system. The exposure of well-developed embryos started at 2 hpf, then 6-BA and/or melatonin were carried out. The results indicated that 6-BA disturbed the rhythmic activities of the larvae, increased wakefulness, correspondingly reduced their rest, and induced disrupted clock gene expression. Video analysis and qRT-PCR data found that zebrafish under 6-BA exposure showed obvious cardiovascular morphological abnormalities and dysfunction, and the mRNA levels of cardiovascular-related genes (nkx2.5, gata4, myl7, vegfaa and vegfab) were significantly down-regulated. In addition, altered thyroid hormone content and hypothalamus-pituitary-thyroid (HPT) axis-related gene expression were also clearly observed. 1umol/L of melatonin had little effect on zebrafish, but its addition could significantly alleviate the circadian disturbance and cardiovascular toxicity caused by 6-BA, and simultaneously played a regulatory role in thyroid system. Our research revealed the adverse effects of 6-BA on zebrafish larvae and the protective role of melatonin in circadian rhythm, cardiovascular and thyroid systems.


Subject(s)
Cardiovascular System , Melatonin , Animals , Benzyl Compounds , Hypothalamus , Purines , Zebrafish
12.
Mikrochim Acta ; 188(9): 289, 2021 08 05.
Article in English | MEDLINE | ID: mdl-34355248

ABSTRACT

A photoelectrochemical (PEC) aptasensor was designed and constructed by Bi24O31Cl10/BiOCl heterojunction as a photoelectric active material for realizing the determination of trace ciprofloxacin (CIP) in water. Compared with Bi24O31Cl10, Bi24O31Cl10/BiOCl heterojunction possessed the improvement of light harvesting and the enhancement of photocurrent signal. The formation of heterojunction between Bi24O31Cl10 and BiOCl can accelerate the transportation efficiency and inhibit the recombination rate of photoinduced carriers. Based on the excellent PEC performance, CIP aptamer was introduced on the modified Bi24O31Cl10/BiOCl/indium tin oxide (ITO) electrode for fabricating a PEC aptasensor. Owing to the combination between aptamer and CIP, CIP-aptamer complex can block the transfer of charge, leading to the reduction of photocurrent response. The PEC aptasensor possessed high sensitivity with a wide detection range (5.0~1.0 × 104 ng L-1) and a low detection limit (1.67 ng L-1, S/N = 3). The PEC aptasensor with good selectivity and reproducibility has been applied to the determination of CIP in water.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Aptamers, Nucleotide/metabolism , Ciprofloxacin/therapeutic use , Electrochemical Techniques/methods , Anti-Bacterial Agents/pharmacology , Ciprofloxacin/pharmacology , Humans
13.
Mol Plant Microbe Interact ; 31(3): 311-322, 2018 03.
Article in English | MEDLINE | ID: mdl-29090631

ABSTRACT

Bacillus cereus AR156 (AR156) is a plant growth-promoting rhizobacterium capable of inducing systemic resistance to Pseudomonas syringae pv. tomato in Arabidopsis thaliana. Here, we show that, when applied to Arabidopsis leaves, AR156 acted similarly to flg22, a typical pathogen-associated molecular pattern (PAMP), in initiating PAMP-triggered immunity (PTI). AR156-elicited PTI responses included phosphorylation of MPK3 and MPK6, induction of the expression of defense-related genes PR1, FRK1, WRKY22, and WRKY29, production of reactive oxygen species, and callose deposition. Pretreatment with AR156 still significantly reduced P. syringae pv. tomato multiplication and disease severity in NahG transgenic plants and mutants sid2-2, jar1, etr1, ein2, npr1, and fls2. This suggests that AR156-induced PTI responses require neither salicylic acid, jasmonic acid, and ethylene signaling nor flagella receptor kinase FLS2, the receptor of flg22. On the other hand, AR156 and flg22 acted in concert to differentially regulate a number of AGO1-bound microRNAs that function to mediate PTI. A full-genome transcriptional profiling analysis indicated that AR156 and flg22 activated similar transcriptional programs, coregulating the expression of 117 genes; their concerted regulation of 16 genes was confirmed by real-time quantitative polymerase chain reaction analysis. These results suggest that AR156 activates basal defense responses to P. syringae pv. tomato in Arabidopsis, similarly to flg22.


Subject(s)
Arabidopsis/immunology , Arabidopsis/microbiology , Bacillus cereus/physiology , Flagellin/pharmacology , Pseudomonas syringae/physiology , Arabidopsis/drug effects , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Bacillus cereus/drug effects , Cyclopentanes/metabolism , Disease Resistance/drug effects , Ethylenes/metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , MicroRNAs/genetics , MicroRNAs/metabolism , Oxylipins/metabolism , Plant Immunity/drug effects , Pseudomonas syringae/drug effects , RNA, Messenger/genetics , RNA, Messenger/metabolism , Salicylic Acid/metabolism , Transcription, Genetic/drug effects
14.
Cell Physiol Biochem ; 44(3): 1051-1063, 2017.
Article in English | MEDLINE | ID: mdl-29179207

ABSTRACT

BACKGROUND/AIMS: Cancer stem cells (CSCs) are considered to be responsible for tumor relapse and metastasis, which serve as a potential therapeutic target for cancer. Aspirin has been shown to reduce cancer risk and mortality, particularly in colorectal cancer. However, the CSCs-suppressing effect of aspirin and its relevant mechanisms in colorectal cancer remain unclear. METHODS: CCK8 assay was employed to detect the cell viability. Sphere formation assay, colony formation assay, and ALDH1 assay were performed to identify the effects of aspirin on CSC properties. Western blotting was performed to detect the expression of the stemness factors. Xenograft model was employed to identify the anti-cancer effects of aspirin in vivo. Unpaired Student t test, ANOVA test and Kruskal-Wallis test were used for the statistical comparisons. RESULTS: Aspirin attenuated colonosphere formation and decreased the ALDH1 positive cell population of colorectal cancer cells. Aspirin inhibited xenograft tumor growth and reduced tumor cells stemness in nude mice. Consistently, aspirin decreased the protein expression of stemness-related transcription factors, including c-Myc, OCT4 and NANOG. Suppression of NANOG blocked the effect of aspirin on sphere formation. Conversely, ectopic expression of NANOG rescued the aspirin-repressed sphere formation, suggesting that NANOG is a key downstream target. Moreover, we found that aspirin repressed NANOG expression in protein level by decreasing its stability. CONCLUSION: We have provided new evidence that aspirin attenuates CSC properties through down-regulation of NANOG, suggesting aspirin as a promising therapeutic agent for colorectal cancer treatment.


Subject(s)
Aspirin/toxicity , Cell Proliferation/drug effects , Nanog Homeobox Protein/metabolism , Animals , Aspirin/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , HCT116 Cells , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Nanog Homeobox Protein/antagonists & inhibitors , Nanog Homeobox Protein/genetics , Neoplastic Stem Cells/cytology , Neoplastic Stem Cells/drug effects , Neoplastic Stem Cells/metabolism , Octamer Transcription Factor-3/metabolism , Protein Stability/drug effects , Proto-Oncogene Proteins c-myc/metabolism , RNA Interference , RNA, Small Interfering/metabolism , SOXB1 Transcription Factors/metabolism , Transplantation, Heterologous
15.
Biochim Biophys Acta Gen Subj ; 1861(7): 1788-1800, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28341484

ABSTRACT

BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR. Co-localization and interaction of RUVBL1 and ITFG1 were determined by immunofluorescence and co-immunoprecipitation. The invasive ability was examined by transwell assay and microfluidic assay. The metastatic and tumorigenic abilities of breast cancer cells were revealed in BALB/c nude mice by xenograft and tail vein injection. RESULTS: ATPase RUVBL1 is highly expressed in breast cancer and predicts the poor prognosis. Elevated expression of RUVBL1 is found in high metastatic breast cancer cells. Silencing RUVBL1 suppresses cancer cell expansion and invasion in vitro and in vivo. RUVBL1 interacts with a conserved transmembrane protein ITFG1 in cytoplasm and plasma membrane to promote the collective invasion. Using a microfluidic model, we demonstrated that silencing RUVBL1 or ITFG1 individually compromises collective invasion of breast cancer cells. CONCLUSION: RUVBL1 is a vital regulator for collective invasion. The interaction between RUVBL1 and ITFG1 is required for breast cancer cell collective invasion and progression. GENERAL SIGNIFICANCE: Targeting collective invasion promoted by RUVBL1-ITFG1 complex provides a novel therapeutic strategy to improve the prognosis of invasive breast cancer.


Subject(s)
Breast Neoplasms/pathology , Carrier Proteins/physiology , DNA Helicases/physiology , Membrane Proteins/physiology , ATPases Associated with Diverse Cellular Activities , Animals , Carrier Proteins/analysis , Cell Line, Tumor , DNA Helicases/analysis , Epithelial-Mesenchymal Transition , Female , Humans , Membrane Proteins/analysis , Mice , Mice, Inbred BALB C , Neoplasm Invasiveness , Neoplasm Metastasis , Protein Binding
16.
Med Res Rev ; 36(6): 1036-1079, 2016 11.
Article in English | MEDLINE | ID: mdl-27406026

ABSTRACT

The Aurora kinase family is comprised of three serine/threonine kinases, Aurora-A, Aurora-B, and Aurora-C. Among these, Aurora-A and Aurora-B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases has been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis. Aurora kinases therefore represent promising targets for anticancer therapeutics. A number of Aurora kinase inhibitors (AKIs) have been generated; some of which are currently undergoing clinical evaluation. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in promoting tumorigenesis, the recent preclinical and clinical AKI data, and potential alternative routes for Aurora-A kinase inhibition.


Subject(s)
Antineoplastic Agents/pharmacology , Aurora Kinase A/antagonists & inhibitors , Aurora Kinase A/genetics , Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Aurora Kinase A/metabolism , Humans , Molecular Targeted Therapy , Neoplasms/enzymology , Neoplasms/genetics , Oncogenes , Protein Kinase Inhibitors/administration & dosage
17.
Infect Drug Resist ; 17: 4161-4165, 2024.
Article in English | MEDLINE | ID: mdl-39347492

ABSTRACT

Introduction: The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) presents a formidable challenge to public health and clinical medicine. This dual phenotype of hypervirulence and multi-drug resistance often complicates treatment options, leaving patients with limited antimicrobial regimens. Consequently, adverse clinical outcomes and high mortality rates are common. Ceftazidime-avibactam (CAZ-AVI) is recognized globally as a critical option for treating infections caused by resistant gram-negative bacteria. Case Report: We present a case of invasive Klebsiella pneumoniae liver abscess syndrome caused by a CR-hvKP infection. The patient exhibited a bloodstream infection, lung and liver abscesses, and suppurative meningitis, eventually developing a brain abscess. Treatment with a combination of meropenem and CAZ-AVI led to a favorable clinical outcome. Conclusion: This case report indicates that combining CAZ-AVI with an antimicrobial agent that is in vitro non-susceptible (carbapenems in this case) is safe and effective for treating severe, multi-site infections caused by CR-hvKP, including central nervous system infections. This case serves as a clinical reference for managing similar patients in practice.

18.
Medicine (Baltimore) ; 103(43): e40034, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39470533

ABSTRACT

OBJECTIVES: To systematically evaluate the qualitative study of nurses' real experience after patient suicide, and to provide theoretical basis for reducing the influence of patient suicide on nurses and reducing the incidence of patient suicide. DESIGN: A systematic review and meta-synthesis of qualitative studies. METHODS: These databases including The Cochrane Library, CINAHL, PubMed, Embase, Web of Science, CMB, CNKI, Wanfang, and VIP were searched by computer to collect relate qualitative researches. The retrieval time was from database established to February 2024. Joanna Briggs Institute Qualitative Research Quality Evaluation Form was used to evaluate the literature quality and Meta-integration. RESULTS: A total of 12 studies were included and 47 results were obtained, which were summarized into 8 new categories and 3 integrated results were obtained. Theme 1: impact on nurses themselves; Theme 2: the nurse's thoughts and suggestions of patient suicide; Theme 3: coping strategy. CONCLUSIONS: Nursing managers should fully pay attention to nurses' feelings and cognitive attitudes after patients' suicide events, strengthen psychological counseling for nurses, so as to reduce the impact of patients' suicide events on nurses.


Subject(s)
Qualitative Research , Suicide , Humans , Suicide/psychology , Nurses/psychology , Adaptation, Psychological , Attitude of Health Personnel
19.
J Vis Exp ; (207)2024 May 10.
Article in English | MEDLINE | ID: mdl-38801269

ABSTRACT

Thread-embedding therapy (TEAT) is a treatment that prevents and manages diseases by inserting a biodegradable suture into an acupoint, providing long-lasting stimulation. TEAT is a simple approach that avoids the discomfort of regular acupuncture and provides sustained therapeutic effects. This article discusses the potential impact of TEAT on the learning and memory abilities of rats with Alzheimer's disease-like symptoms. Since chemically induced neuronal degeneration and cognitive impairments in rats does not entirely reflect the true pathological changes observed in Alzheimer's disease. Consequently, our research group has designated these manifestations as Alzheimer's disease-like symptoms. A protocol has been established to outline the selection of acupoints, the operation process, and necessary precautions for the head and lower back. The experiment was conducted on three groups: a control group, a model group, and a TEAT group, each containing 6 rats. To induce Alzheimer's disease-like symptoms, rats were intraperitoneally injected with D-galactose for 7 weeks (49 days). The rats in the TEAT group received acupoint catgut embedding treatment. Following the intervention period, a Morris Water Maze (MWM) was conducted to evaluate the rats' learning and memory. Subsequently, the rats were sacrificed, and their brain tissue was examined. A histological examination was performed to understand the effects of TEAT on the pathology of rats exhibiting symptoms of Alzheimer's disease. This study suggests that TEAT may improve learning and memory in rats with Alzheimer's disease-like symptoms, indicating a potentially promising new treatment approach for this neurodegenerative condition.


Subject(s)
Acupuncture Therapy , Alzheimer Disease , Animals , Alzheimer Disease/therapy , Acupuncture Therapy/methods , Rats , Disease Models, Animal , Acupuncture Points , Sutures , Male , Rats, Sprague-Dawley , Maze Learning/physiology
20.
Sci Total Environ ; 912: 169358, 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38135064

ABSTRACT

Grazing exclusion has been implemented worldwide as a nature-based solution for restoring degraded grassland ecosystems that arise from overgrazing. However, the effect of grazing exclusion on soil nitrogen cycle processes, subsequent greenhouse gas emissions and underlying mechanisms remain unclear. Here, we investigated the effect of four-year grazing exclusion on plant communities, soil properties, and soil nitrogen cycle-related functional gene abundance in an alpine meadow on the Qinghai-Tibet Plateau. Using an automated continuous-flow incubation system, we performed an incubation experiment and measured soil-borne N2O, N2, and CO2 fluxes to three successive "hot moment" events (precipitation, N deposition, and oxic-to-anoxic transition) between grazing-excluded and grazing soil. Higher soil N contents (total nitrogen, NH4+, NO3-) and extracellular enzyme activities (ß-1,4-glucosidase, ß-1,4-N-acetyl-glucosaminidase, cellobiohydrolase) are observed under grazing exclusion. The aboveground and litter biomass of plant community was significantly increased by grazing exclusion, but grazing exclusion decreased the average number of plant species and microbial diversity. The N2O + N2 fluxes observed under grazing exclusion were higher than those observed under free grazing. The N2 emissions and N2O/(N2O + N2) ratios observed under grazing exclusion were higher than those observed under free grazing in oxic conditions. Instead, higher N2O fluxes and lower denitrification functional gene abundances (nirS, nirK, nosZ, and nirK + nirS) under anoxia were found under grazing exclusion than under free grazing. The N2O site-preference value indicates that under grazing exclusion, bacterial denitrification contributes more to higher N2O production compared with under free grazing (81.6 % vs. 59.9 %). We conclude that grazing exclusion could improve soil fertility and plant biomass, nevertheless it may lower plant and microbial diversity and increase potential N2O emission risk via the alteration of the denitrification end-product ratio. This indicates that not all grassland management options result in a mutually beneficial situation among wider environmental goals such as greenhouse gas mitigation, biodiversity, and social welfare.


Subject(s)
Denitrification , Greenhouse Gases , Tibet , Ecosystem , Grassland , Soil , Soil Microbiology , Nitrous Oxide/analysis
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