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1.
Nanomaterials (Basel) ; 14(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38668199

RESUMO

Manipulating plasmonic chirality has shown promising applications in nanophotonics, stereochemistry, chirality sensing, and biomedicine. However, to reconfigure plasmonic chirality, the strategy of constructing chiral plasmonic systems with a tunable morphology is cumbersome and complicated to apply for integrated devices. Here, we present a simple and effective method that can also manipulate chirality and control chiral light-matter interactions only via strong coupling between chiral plasmonic nanoparticles and excitons. This paper presents a chiral plexcitonic system consisting of L-shaped nanorod dimers and achiral molecule excitons. The circular dichroism (CD) spectra in our strong-coupling system can be calculated by finite element method simulations. We found that the formation of the chiral plexcitons can significantly modulate the CD spectra, including the appearance of new hybridized peaks, double Rabi splitting, and bisignate anti-crossing behaviors. This phenomenon can be explained by our extended coupled-mode theory. Moreover, we explored the applications of this method in enantiomer ratio sensing by using the properties of the CD spectra. We found a strong linear dependence of the CD spectra on the enantiomer ratio. Our work provides a facile and efficient method to modulate the chirality of nanosystems, deepens our understanding of chiral plexcitons in nanosystems, and facilitates the development of chiral devices and chiral sensing.

2.
Opt Express ; 32(7): 11522-11533, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570997

RESUMO

Hybrid quasiparticles produced by the strong interaction between nanostructures and excitons will exhibit optical chirality when one of the coupled components is chiral. Due to the tunability of hybrid states, the coupled system has potential applications in chiral devices and chiral sensing. However, reported chiral materials including chiral molecules and three-dimensional chiral structures in the coupled system limit the application due to the weak chiroptical responses and difficult fabrication, respectively. In this paper, we design chiral quasibound states in the continuum (q-BIC) metasurface by introducing planar symmetry-breaking and z-axis perturbation into an array structure whose unit cell is a C4 rotational symmetric disk. By tuning the polarization state of the eigenmode, a significant chiroptical response is obtained in our q-BIC metasurface. Furthermore, mode splitting is observed not only in the reflection spectrum but also in the circular dichroism (CD) spectrum in the chiral q-BIC and monolayer WS2 strong coupling system, which indicates the realization of the exciton-polariton optical chirality. More importantly, one order of magnitude difference in the reflection to left and right circularly polarized light is achieved resulting in significant CD signals. Our work provides a new strategy to realize the exciton polaritons with significant chiroptical responses, which exhibits promising applications in on-chip chiral devices.

3.
J Mol Neurosci ; 74(2): 39, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581598

RESUMO

Previous studies have indicated a potential relationship between zinc and epilepsy. The aim of this study is to investigate the causal relationship between zinc, zinc-dependent carbonic anhydrase, and gray matter volume in brain regions enriched with zinc and epilepsy, as well as explore the possible mechanisms by which zinc contributes to epilepsy. First, this study assessed the risk causality between zinc, carbonic anhydrase, and gray matter volume alterations in zinc-enriched brain regions and various subtypes of epilepsy based on Two-sample Mendelian randomization analysis. And then, this study conducted GO/KEGG analysis based on colocalization analysis, MAGMA analysis, lasso regression, random forest model, and XGBoost model. The results of Mendelian randomization analyses showed a causal relationship between zinc, carbonic anhydrase-4, and generalized epilepsy (p = 0.044 , p = 0.010). Additionally, carbonic anhydrase-1 and gray matter volume of the caudate nucleus were found to be associated with epilepsy and focal epilepsy (p = 0.014, p = 0.003 and p = 0.022, p = 0.009). A colocalization relationship was found between epilepsy and focal epilepsy (PP.H4.abf = 97.7e - 2). Meanwhile, the MAGMA analysis indicated that SNPs associated with epilepsy and focal epilepsy were functionally localized to zinc-finger-protein-related genes (p < 1.0e - 5). The genes associated with focal epilepsy were found to have a molecular function of zinc ion binding (FDR = 2.3e - 6). After the onset of epilepsy, the function of the gene whose expression changed in the rats with focal epilepsy was enriched in the biological process of vascular response (FDR = 4.0e - 5). These results revealed mechanism of the increased risk of epilepsy caused by elevated zinc may be related to the increase of zinc ion-dependent carbonic anhydrase or the increase of the volume of zinc-rich caudate gray matter.


Assuntos
Anidrases Carbônicas , Epilepsias Parciais , Epilepsia , Ratos , Animais , Zinco/metabolismo , Anidrases Carbônicas/genética , Anidrases Carbônicas/análise , Anidrases Carbônicas/metabolismo , Encéfalo/metabolismo , Epilepsia/genética
4.
Acta Trop ; 254: 107188, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38531428

RESUMO

Cryptosporidium spp. and G. duodenalis often infect humans, cats, and other mammals, causing diarrhea and being responsible for numerous outbreaks of waterborne and foodborne infections worldwide. The rapid increase in the number of pet cats poses a substantial public health risk. However, there were few reports about the infection of Cryptosporidium spp. and G. duodenalis infections in pet cats in Henan Province, central China. Thus, to understand the prevalence and genetic distribution of Cryptosporidium spp. and G. duodenalis in pet cats, and to evaluate the zoonotic potential, possible transmission routes and public health implications of isolates, fecal samples (n = 898) were randomly collected from pet cats in 11 cities in Henan Province, central China. Nested PCR based on the SSU rRNA gene and bg gene was used to the prevalence of Cryptosporidium spp. and G. duodenalis, respectively. The prevalence was 0.8 % (7/898) and 2.0 % (18/898) for Cryptosporidium spp. and G. duodenalis respectively. Additionally, the Cryptosporidium spp. positive isolates were identified as C. parvum subtype IIdA19G1 by gp60 gene. In the present study, the IIdA19G1 subtype was discovered in pet cats for the first time in China, enriching the information on the host type and geographical distribution of Cryptosporidium spp. in China. For G. duodenalis, a total of 18 G. duodenalis positive samples were identified, belonging to four assemblages: a zoonotic assemblage A1 (4/898), three host-specific assemblages C (8/898), D (5/898), and F (1/898). Interestingly, we found that pet cats infected with Cryptosporidium spp. and G. duodenalis are more likely to experience emaciation symptoms compared to the negative group. More importantly, the prevalence of Cryptosporidium spp. and G. duodenalis detected in the present study were low, but the subtype IIdA19G1 of Cryptosporidium spp. and the assemblages A1, C, D, and F of G. duodenalis have the potential for zoonotic transmission. Thus, we should focus on preventing and controlling the risk of cross-species transmission that may occur in pet cats in Henan Province.

5.
Acta Trop ; 253: 107175, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38492874

RESUMO

Cyclospora cayetanensis (C. cayetanensis) is a significant pathogen that causes diarrheal illness and causes large foodborne diarrhea outbreaks in the USA and Canada. However, there is currently a lack of published meta-analysis on the prevalence of C. cayetanensis infection in the global population. A real estimation of a disease prevalence should always be done on the basis of studies designed for that purpose. We conducted a comprehensive search of various databases for articles pertaining to the prevalence of C. cayetanensis infection in humans, spanning from the inception of these databases to March 10, 2023. Utilizing a random effects model, we estimated the prevalence of C. cayetanensis infection in humans. Our analysis included a total of 150 datasets sourced from 42 different countries, which were ultimately selected for the final quantitative assessment. The prevalence of C. cayetanensis infection in humans worldwide was estimated to be 3.4 % (5636/166,611). Notably, Africa exhibited the highest prevalence rate at 5.9 % (606/11,068). Further subgroup analysis revealed a significantly higher infection rate in humans residing in low-income countries (7.6 %, 83/921) compared to those in lower-middle-income countries (4.8 %, 3280/48,852), upper-middle-income countries (2.9 %, 2194/99,419), and high-income countries (0.4 %, 79/17,419). The results indicate that the global prevalence of C. cayetanensis infection in humans is relatively low, despite its extensive geographical distribution and children were found to be more susceptible to C. cayetanensis infection compared to those adults. Sensitivity analysis revealed that one study significantly affects the prevalence of C. cayetanensis, which was adjusted to 2.9 % (4017/160,049; 95 % CI: 2.7-3.1 %) by excluding this study. The findings highlight the relatively high prevalence of C. cayetanensis infection in low-income countries and among humans with diarrhea, particularly in Africa. Consequently, routine surveillance for intestinal protozoa is crucial in these regions.


Assuntos
Cyclospora , Ciclosporíase , Humanos , África/epidemiologia , Ciclosporíase/epidemiologia , Ciclosporíase/complicações , Ciclosporíase/parasitologia , Diarreia/parasitologia , Fezes/parasitologia , Prevalência
6.
ACS Omega ; 9(6): 6924-6931, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38371847

RESUMO

Blockage is often generated in the air nozzle guide duct in a circulating fluidized-bed coal gasifier (CFBG), especially with Zhundong sub-bituminous coal (ZSBC) as the raw material. A typical example is found in one CFBG sample from Xinjiang Yihua Chemical Industry Co, Ltd. The serious blockage can be observed obviously. As so far, it is not clear for the characteristics and generation mechanism of the blockage. For analysis, the blockage can be classified into two parts, wall-layer blockage (WLB) and center-layer blockage (CLB). To inhibit its formation, it is of significance to analyze the composition, surface morphology, and formation mechanism of the two blockages. In our experiments, WLB and CLB were tested by XRF, XRD, FTIR, SEM-EDS, and SEM-mapping methods. Results showed that WLB presents high content of Fe, Cr, and Ni, and Fe mainly existed in the form of metal oxides. CLB is dominated by Si (43.04%), derived from silica and alkali and alkaline-earth metals silicates, and the migration of Fe, Cr, and Ni elements from the duct material was observed. Compared with WLB, from FTIR analysis, CLB contains more inorganic minerals, and the absorption peak of inorganic minerals is mainly attributed to asymmetric Si-O-Si. Many fine particles are attached to the surface of the WLB, while the surface of the CLB is smooth, and there is noticeable raised texture, which is presumed to be the result of particle melting and agglomerating as the bottom ash enters the duct in the gasification process. For the formation of the blockage, this paper speculates that it is mainly due to the difference in flow resistance near the air nozzle outlet, resulting in the formation of a flow dead zone at the bottom of the gasifier, which leads to large amounts of ash overcoming the outlet resistance and leaking into the air nozzle, and next, the ash corrodes in the tube, resulting in wall deposition and ultimately blocking the air guide duct. Two methods can be tried to avoid or inhibit the formation of blockage in the duct, including optimizing air nozzle with more wear-resistant and heat-resistant materials and adjusting the distance between air nozzles to avoid mutual interference from ash particles.

7.
Cancer Gene Ther ; 31(4): 562-573, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267624

RESUMO

Ran GTPase activating protein 1 (RanGAP1) has been implicated in various diseases, but its role in colorectal cancer (CRC) progression remains unclear. Using tumor tissues and public databases, we found that RanGAP1 was significantly upregulated in CRC tissues and was associated with poor prognosis of patients. N6-methyladenosine (m6A) was found to play an important role in higher expression of RanGAP1. MeRIP-seq, RIP-qPCR, Luciferase reporter assays and other related experiment elucidated the molecular mechanism underlying m6A modification of RanGAP1. Besides, cell function experiments and xenograft tumor models corroborated the function of RanGAP1 in CRC progression. By RNA-seq and related analysis, RanGAP1 was verified to influent CRC progression via the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Therefore, N6-methyladenosine modification of RanGAP1 by METTL3/YTHDF1 plays a role in CRC progression through the MAPK pathway and could be a potential biomarker and therapeutic target for CRC. Schematic diagram showed that N6-methyladenosine modification of RanGAP1 promotes CRC progression via the MAPK signaling pathway.


Assuntos
Neoplasias Colorretais , Proteínas Quinases Ativadas por Mitógeno , Humanos , Animais , Sistema de Sinalização das MAP Quinases , Adenosina/genética , Modelos Animais de Doenças , Proteínas Ativadoras de GTPase , Neoplasias Colorretais/genética , Metiltransferases/genética , Proteínas de Ligação a RNA
8.
Cell ; 187(1): 184-203.e28, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38181741

RESUMO

We performed comprehensive proteogenomic characterization of small cell lung cancer (SCLC) using paired tumors and adjacent lung tissues from 112 treatment-naive patients who underwent surgical resection. Integrated multi-omics analysis illustrated cancer biology downstream of genetic aberrations and highlighted oncogenic roles of FAT1 mutation, RB1 deletion, and chromosome 5q loss. Two prognostic biomarkers, HMGB3 and CASP10, were identified. Overexpression of HMGB3 promoted SCLC cell migration via transcriptional regulation of cell junction-related genes. Immune landscape characterization revealed an association between ZFHX3 mutation and high immune infiltration and underscored a potential immunosuppressive role of elevated DNA damage response activity via inhibition of the cGAS-STING pathway. Multi-omics clustering identified four subtypes with subtype-specific therapeutic vulnerabilities. Cell line and patient-derived xenograft-based drug tests validated the specific therapeutic responses predicted by multi-omics subtyping. This study provides a valuable resource as well as insights to better understand SCLC biology and improve clinical practice.


Assuntos
Neoplasias Pulmonares , Proteogenômica , Carcinoma de Pequenas Células do Pulmão , Humanos , Linhagem Celular , Neoplasias Pulmonares/química , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/química , Carcinoma de Pequenas Células do Pulmão/genética , Xenoenxertos , Biomarcadores Tumorais/análise
9.
Chem Commun (Camb) ; 60(10): 1329-1332, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38197300

RESUMO

An electrochemical method for the decarboxylative alkylation of ß-ketoacids with phenol derivatives has been developed. The protocol was carried out in readily available unseparated cells at room temperature in the absence of catalysts and oxidants. The corresponding aryl ketones were obtained in satisfactory yields without additional electrolytes, and were easy to produce in gram-scale synthesis. Based on control experiments and cyclic voltammetry, a plausible reaction mechanism was proposed.

10.
One Health ; 17: 100651, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38116451

RESUMO

Giardia duodenalis is one of the major causes of diarrhea among humans, especially in young children. Statistical analysis revealed that the pooled prevalence of G. duodenalis in humans, dogs, and cats was 9.72% (10,921/112383), 15.60% (7510/48140), and 14.53% (1125/7740), respectively. Unquestionably, the canine-specific assemblages C and D and the feline-specific assemblage F were the dominant genotypes in dogs and cats, respectively. Additionally, the prevalence of zoonotic G. duodenalis assemblages (A and B) in dogs and cats was 23.07% (875/3792) and 41.42% (169/408), respectively, implying that the potential transmission of G. duodenalis from dogs and cats to human infection cannot be ignored. The highest frequency of potentially zoonotic assemblages was found among working dogs (3.55%, 25/705) and the 1-5 age group (22.92%, 11/48). In summary, dogs and cats have a significant role in the zoonotic transmission of G. duodenalis due to their close contact with humans and the higher frequency presence of zoonotic assemblages. Further studies are necessary to explore the presence of G. duodenalis among humans and animals and in environmental samples. Researchers should adopt a one-health approach to gain a deeper understanding of G. duodenalis in dogs and cats and potential transmission routes to humans.

11.
Sci Transl Med ; 15(727): eade0054, 2023 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-38117903

RESUMO

Vaccination has substantially reduced the morbidity and mortality of bacterial diseases, but mechanisms of vaccine-elicited pathogen clearance remain largely undefined. We report that vaccine-elicited immunity against invasive bacteria mainly operates in the liver. In contrast to the current paradigm that migrating phagocytes execute vaccine-elicited immunity against blood-borne pathogens, we found that invasive bacteria are captured and killed in the liver of vaccinated host via various immune mechanisms that depend on the protective potency of the vaccine. Vaccines with relatively lower degrees of protection only activated liver-resident macrophage Kupffer cells (KCs) by inducing pathogen-binding immunoglobulin M (IgM) or low amounts of IgG. IgG-coated pathogens were directly captured by KCs via multiple IgG receptors FcγRs, whereas IgM-opsonized bacteria were indirectly bound to KCs via complement receptors of immunoglobulin superfamily (CRIg) and complement receptor 3 (CR3) after complement C3 activation at the bacterial surface. Conversely, the more potent vaccines engaged both KCs and liver sinusoidal endothelial cells by inducing higher titers of functional IgG antibodies. Endothelial cells (ECs) captured densely IgG-opsonized pathogens by the low-affinity IgG receptor FcγRIIB in a "zipper-like" manner and achieved bacterial killing predominantly in the extracellular milieu via an undefined mechanism. KC- and endothelial cell-based capture of antibody-opsonized bacteria also occurred in FcγR-humanized mice. These vaccine protection mechanisms in the liver not only provide a comprehensive explanation for vaccine-/antibody-boosted immunity against invasive bacteria but also may serve as in vivo functional readouts of vaccine efficacy.


Assuntos
Células de Kupffer , Vacinas , Animais , Camundongos , Células de Kupffer/metabolismo , Células Endoteliais , Macrófagos/metabolismo , Imunoglobulina G/metabolismo , Fígado , Anticorpos Antivirais/metabolismo , Imunoglobulina M/metabolismo , Receptores de IgG/metabolismo , Bactérias
12.
Nano Lett ; 23(20): 9428-9436, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37823692

RESUMO

Chiral plexcitons, produced by the strong interaction between plasmonic nanocavities and chiral molecules, can provide a promising direction for controlling chiroptical responses on the nanoscale. Here, we reveal the chiral origin and electromagnetic hybridization process in chiral strongly coupled systems. The mechanism and unique advantages of chiral plexcitons for fine-tuning circular dichroism (CD) responses are demonstrated, providing a rule for controlling chiral light-matter interactions in complex chiral nanosystems. Furthermore, we experimentally demonstrate the fine-tuning of chiral plexcitons in hybrid systems consisting of plasmonic nanoparticles and chiral J-aggregates. Continuous and precise tuning of the CD resonance positions was successfully achieved in a given structure. Compared with the previous work, the CD spectral tuning accuracy has been improved by an order of magnitude, which can reach the level of 1 nm. Our findings provide a feasible strategy and theoretical basis for accurately controlling chirality in multiple dimensions.

13.
Opt Express ; 31(20): 32082-32092, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37859018

RESUMO

Chiral plexcitonic systems exhibit a novel chiroptical phenomenon, which can provide a new route to design chiroptical devices. Reported works focused on the two-mode strong coupling between chiral molecules and nanoparticles, while multiple-mode coupling can provide richer modulation. In this paper, we proposed a three-mode coupling system consisting of a chiral Au helices array, a Fabry-Pérot cavity, and monolayer WSe2, which can provide an extra chiral channel, a more widely tunable region, and more tunable methods compared to two-mode coupled systems. The optical response of this hybrid system was investigated based on the finite element method. Mode splitting observed in the circular dichroism (CD) spectrum demonstrated that the chiroptical response successfully shifted from the resonant position of the chiral structure to three plexcitons through strong coupling, which provided a new route for chiral transfer. Furthermore, we used the coupled oscillator model to obtain the energy and Hopfield coefficients of the plexciton branches to explain the chiroptical phenomenon of the hybrid system. Moreover, the tunability of the hybrid system can be achieved by tuning the temperature and period of the helices array. Our work provides a feasible strategy for chiral sensing and modulation devices.

14.
BMC Genomics ; 24(1): 635, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37875797

RESUMO

BACKGROUND: With the promotion of "One Health," the health of animals and their impact on the environment have become major concerns recently. Widely distributed in China, the whooper swans (Cygnus cygnus) and black swans (Cygnus atratus) are not only important to the ecological environment, but they may also potentially influence public health security. The metagenomic approach was adopted to uncover the impacts of the gut microbiota of swans on host and public health. RESULTS: In this study, the intestinal microbiome and resistome of migratory whooper swans and captive-bred black swans were identified. The results revealed similar gut microbes and functional compositions in whooper and black swans. Interestingly, different bacteria and probiotics were enriched by overwintering whooper swans. We also found that Acinetobacter and Escherichia were significantly enriched in early wintering period swans and that clinically important pathogens were more abundant in black swans. Whooper swans and black swans are potential reservoirs of antibiotic resistance genes (ARGs) and novel ARGs, and the abundance of novel ARGs in whooper swans was significantly higher than that in black swans. Metagenomic assembly-based host tracking revealed that most ARG-carrying contigs originated from Proteobacteria (mainly Gammaproteobacteria). CONCLUSIONS: The results revealed spatiotemporal changes in microbiome and resistome in swans, providing a reference for safeguarding public health security and preventing animal epidemics.


Assuntos
Anseriformes , Microbioma Gastrointestinal , Microbiota , Saúde Única , Animais , Microbioma Gastrointestinal/genética , China , Patos , Antibacterianos/farmacologia
15.
J Immunother Cancer ; 11(9)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37739440

RESUMO

BACKGROUND: Pancreatic cancer (PAC) is one of the most malignant cancer types and immunotherapy has emerged as a promising treatment option. PAC cells undergo metabolic reprogramming, which is thought to modulate the tumor microenvironment (TME) and affect immunotherapy outcomes. However, the metabolic landscape of PAC and its association with the TME remains largely unexplored. METHODS: We characterized the metabolic landscape of PAC based on 112 metabolic pathways and constructed a novel metabolism-related signature (MBS) using data from 1,188 patients with PAC. We evaluated the predictive performance of MBS for immunotherapy outcomes in 11 immunotherapy cohorts from both bulk-RNA and single-cell perspectives. We validated our results using immunohistochemistry, western blotting, colony-formation assays, and an in-house cohort. RESULTS: MBS was found to be negatively associated with antitumor immunity, while positively correlated with cancer stemness, intratumoral heterogeneity, and immune resistant pathways. Notably, MBS outperformed other acknowledged signatures for predicting immunotherapy response in multiple immunotherapy cohorts. Additionally, MBS was a powerful and robust biomarker for predicting prognosis compared with 66 published signatures. Further, we identified dasatinib and epothilone B as potential therapeutic options for MBS-high patients, which were validated through experiments. CONCLUSIONS: Our study provides insights into the mechanisms of immunotherapy resistance in PAC and introduces MBS as a robust metabolism-based indicator for predicting response to immunotherapy and prognosis in patients with PAC. These findings have significant implications for the development of personalized treatment strategies in patients with PAC and highlight the importance of considering metabolic pathways and immune infiltration in TME regulation.


Assuntos
Imunoterapia , Neoplasias Pancreáticas , Humanos , Consenso , Neoplasias Pancreáticas/terapia , Aprendizado de Máquina , Microambiente Tumoral , Neoplasias Pancreáticas
16.
Exp Hematol Oncol ; 12(1): 77, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679762

RESUMO

BACKGROUND: UTX (encoded by KDM6A), a histone demethylase for H3K27me2/3, is frequently mutated in human cancers. However, its functional and regulatory mechanisms in colorectal cancer (CRC) remain unclear. METHODS: Immunohistochemistry staining was used to investigate the clinical relevance of UTX in CRC. Additionally, we generated a spontaneous mouse CRC model with conditional Utx knockout to explore the role of UTX in the colorectal tumorigenesis. Post-translational regulation of UTX was determined by co-immunoprecipitation and immunoblot analyses. RESULTS: Herein, we identify that downregulation of UTX, mediated by the Cullin 4B-DNA Damage Binding Protein-1-Constitutive Photomorphogenesis Protein 1 (CUL4B-DDB1-COP1) complex, promotes CRC progression. Utx deletion in intestinal epithelial cells enhanced the susceptibility to tumorigenesis in AOM/DSS-induced spontaneous mouse CRC model. However, this effect is primarily alleviated by GSK126, an inhibitor of histone methyltransferase EZH2. Mechanistically, EMP1 and AUTS2 are identified as putative UTX target genes mediating UTX functions in limiting intestinal tumorigenesis. Notably, the CUL4B-DDB1-COP1 complex is identified as the functional E3 ligase responsible for targeting UTX for degradation in CRC cells. Thus, Cop1 deficiency in mouse intestinal tissue results in UTX accumulation and restricts tumorigenesis. Furthermore, patient cohort analysis reveals that UTX expression is negatively correlated with clinical stage, favorable disease outcomes, and COP1 expression. CONCLUSIONS: In the current study, the tumor suppressor function and regulation of UTX in CRC provide a molecular basis and the rationale to target EZH2 in UTX-deficient CRC.

17.
Int J Nanomedicine ; 18: 4485-4505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576462

RESUMO

Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH2, and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches.


Assuntos
Poloxâmero , Cicatrização , Polietilenos/farmacologia , Hidrogéis/farmacologia
18.
Exp Parasitol ; 253: 108603, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37633513

RESUMO

Cryptosporidiosis is a zoonotic disease in humans and animals that is caused by infection with the oocysts of Cryptosporidium. MicroRNAs (miRNAs) are important players in regulating the innate immune response against parasitic infection. Public miRNAs data for studying pathogenic mechanisms of cryptosporidiosis, particularly in natural hosts, are scarce. Here, we compared miRNA profiles of the glandular stomach of C. muris-infected and uninfected BALB/c mice using microarray sequencing. A total of 10 miRNAs (including 3 upregulated and 7 downregulated miRNAs) with significant differential expression (|FC| ≥ 2 and P value < 0.05) were identified in the glandular stomach of BALB/c mice 8 h after infection with C. muris. MiRWalk and miRDB online bioinformatics tools were used to predict the target genes of differentially expressed miRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to annotate the target genes. GO analysis indicate that gene transcription-related and ion transport-related GO terms were significantly enriched. In addition, the KEGG analyses showed that the target genes were strongly related to diverse types of tumor disease progression and anti-pathogen immunity pathways. In the current study, we firstly report changes in miRNA expression profiles in the glandular stomach of BALB/c mice at the early phase of C. muris invasion. This dysregulation in miRNA expression may contribute to our understanding of cryptosporidiosis pathology. This study provides a new perspective on the miRNA regulatory mechanisms of cryptosporidiosis, which may help in the development of effective control strategies against this pathogen.


Assuntos
Criptosporidiose , Cryptosporidium , MicroRNAs , Animais , Humanos , Camundongos , Biologia Computacional , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Estômago
19.
Parasit Vectors ; 16(1): 257, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37525231

RESUMO

BACKGROUND: A close connection between a protozoan parasite and the balance of the other gut microbes of the host has been demonstrated. The calves may be naturally co-infected with many parasites, and the co-effects of parasites on other intestinal microbes of calves remain unclear. This study aims to preliminarily reveal the relationship between intestinal parasites and other intestinal microbes in calves. METHODS: Fecal samples were collected from four calves with bloody diarrhea, four calves with watery diarrhea, and seven normal calves, and the microbial flora of the samples were analyzed by whole-genome sequencing. Protozoal parasites were detected in the metagenome sequences and identified using polymerase chain reaction (PCR). RESULTS: Cryptosporidium, Eimeria, Giardia, Blastocystis, and Entamoeba were detected by metagenomic analysis, and the identified species were Giardia duodenalis assemblage E, Cryptosporidium bovis, Cryptosporidium ryanae, Eimeria bovis, Eimeria subspherica, Entamoeba bovis, and Blastocystis ST2 and ST10. Metagenomic analysis showed that the intestinal microbes of calves with diarrhea were disordered, especially in calves with bloody diarrhea. Furthermore, different parasites show distinct relationships with the intestinal microecology. Cryptosporidium, Eimeria, and Giardia were negatively correlated with various intestinal bacteria but positively correlated with some fungi. However, Blastocystis and Entamoeba were positively associated with other gut microbes. Twenty-seven biomarkers not only were significantly enriched in bloody diarrhea, watery diarrhea, and normal calves but were also associated with Eimeria, Cryptosporidium, and Giardia. Only Eimeria showed a distinct relationship with seven genera of bacteria, which were significantly enriched in the healthy calves. All 18 genera of fungi were positively correlated with Cryptosporidium, Eimeria, and Giardia, which were also significantly enriched in calves with bloody diarrhea. Functional genes related to parasites and diseases were found mainly in fungi. CONCLUSIONS: This study revealed the relationship between intestinal protozoan parasites and the other calf gut microbiome. Different intestinal protozoan parasites have diametrically opposite effects on other gut microecology, which not only affects bacteria in the gut, but also is significantly related to fungi and archaea.


Assuntos
Blastocystis , Criptosporidiose , Cryptosporidium , Eimeria , Entamoeba , Giardia lamblia , Giardíase , Enteropatias Parasitárias , Parasitos , Animais , Bovinos , Parasitos/genética , Criptosporidiose/parasitologia , Cryptosporidium/genética , Metagenoma , Enteropatias Parasitárias/veterinária , Giardíase/veterinária , Giardíase/parasitologia , Giardia/genética , Giardia lamblia/genética , Blastocystis/genética , Eimeria/genética , Entamoeba/genética , Fezes/parasitologia , Diarreia/veterinária , Diarreia/parasitologia
20.
Infect Genet Evol ; 113: 105482, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451417

RESUMO

Giardia is a genus of flagellated protozoan parasites that infect the small intestine of humans and animals, causing the diarrheal illness known as giardiasis. Giardia exhibits significant genetic diversity among its isolates, which can have important implications for disease transmission and clinical presentation. This diversity is influenced by the coevolution of Giardia with its host, resulting in the development of unique genetic assemblages with distinct phenotypic characteristics. Although panmixia has not been observed, some assemblages appear to have a broader host range and exhibit higher transmission rates. Molecular diagnostic methods enable researchers to examine the genetic diversity of Giardia populations, enhancing our understanding of the genetic diversity, population structure, and transmission patterns of this pathogen and providing insights into clinical presentations of giardiasis.


Assuntos
Variação Genética , Giardia , Giardíase , Giardia/genética , Giardíase/diagnóstico , Humanos , Adaptação Fisiológica , DNA de Protozoário/genética , Animais , Ribossomos/genética , Ribossomos/metabolismo
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