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1.
Clinics (Sao Paulo) ; 79: 100374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38718696

RESUMO

OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Masculino , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Prognóstico , Adulto , Idoso , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Programa de SEER
2.
Chemistry ; 30(28): e202400527, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38470123

RESUMO

Owing to distinct physicochemical properties in comparison to gold and silver counterparts, atomically precise copper nanoclusters are attracting embryonic interest in material science. The introduction of copper cluster nanomaterials in more interesting fields is currently urgent and desired. Reported in this work are novel copper nanoclusters of [XCu54Cl12(tBuS)20(NO3)12] (X=S or none, tBuSH=2-methyl-2-propanethiol), which exhibit high performance in photothermal conversion. The clusters have been prepared in one pot and characterized by combinatorial techniques including ultraviolet-visible spectroscopy (UV-vis), electrospray ionization mass spectrometry (ESI-MS), and X-ray photoelectron spectroscopy (XPS). The molecular structure of the clusters, as revealed by single crystal X-ray diffraction analysis (SCXRD), shows the concentric three-shell Russian doll arrangement of X@Cu14@Cl12@Cu40. Interestingly, the [SCu54Cl12(tBuS)20(NO3)12] cluster contains 8 free valence electrons in its structure, making it the first eight-electron copper nanocluster stabilized by thiolates. More impressively, the clusters possess an effective photothermal conversion (temperature increases by 71 °C within ~50 s, λex=445 nm, 0.5 W cm-2) in a wide wavelength range (either blue or near-infrared). The photothermal conversion can be even driven under irradiation of simulated sunlight (3 sun), endowing the clusters with great potency in solar energy utilization.

3.
J Control Release ; 368: 623-636, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38479445

RESUMO

Chemoresistance to cisplatin remains a significant challenge affecting the prognosis of advanced oral squamous cell carcinoma (OSCC). However, the specific biomarkers and underlying mechanisms responsible for cisplatin resistance remain elusive. Through comprehensive bioinformatic analyses, we identified a potential biomarker, BCL2 associated athanogene-1 (BAG1), showing elevated expression in head and neck squamous cell carcinoma (HNSCC). Since OSCC represents the primary pathological type of HNSCC, we investigated BAG1 expression in human tumor tissues and cisplatin resistant OSCC cell lines, revealing that silencing BAG1 induced apoptosis in cisplatin-resistant cells both in vitro and in vivo. This effect led to impaired cell viability of cisplatin resistant OSCC cells and indicated a positive correlation between BAG1 expression and the G1/S transition during cell proliferation. Based on these insights, the administration of a CDK4/6 inhibitor in combination with cisplatin effectively overcame cisplatin resistance in OSCC through the CDK4/6-BAG1 axis. Additionally, to enable simultaneous drug delivery and enhance synergistic antitumor efficacy, we developed a novel supramolecular nanodrug LEE011-FFERGD/CDDP, which was validated in an OSCC orthotopic mouse model. In summary, our study highlights the potential of a combined administration of CDK4/6 inhibitor and cisplatin as a promising therapeutic regimen for treating advanced or cisplatin resistant OSCC.


Assuntos
Carcinoma de Células Escamosas , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Resistencia a Medicamentos Antineoplásicos , Neoplasias Bucais , Nanopartículas , Animais , Humanos , Camundongos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Quinase 6 Dependente de Ciclina/antagonistas & inibidores
4.
ACS Biomater Sci Eng ; 10(4): 2523-2533, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38445444

RESUMO

Regenerating the pulp-dentin complex remains a decisive factor during apexification for immature permanent teeth. Peptide KN-17, which was modified based on the structure of cecropin B, could effectively interfere with bacterial growth and induce the migration of human bone marrow stromal cells (hBMSCs). This study aimed to investigate the effect of KN-17 on the tissue regeneration. To our surprise, KN-17 can significantly stimulate angiogenesis in vitro and in vivo, which may provide a guarantee for apical closure. Herein, a novel peptide/KN-17 coassembled hydrogel is developed via a heating-cooling process. Npx-FFEY/KN-17 supramolecular hydrogel can induce vessel development, stimulate odontogenic differentiation of human dental pulp stem cells (hDPSCs), and exert an antibacterial effect on Enterococcus faecalis (E. faecalis). Furthermore, coronal pulp excised rat molars are supplied with KN-17 or KN-17-loaded hydrogel and transplanted subcutaneously in BALB/c-nu mice. After 4 weeks, the hydrogel Npx-FFEY/KN-17 stimulates the formation of multiple odontoblast-like cells and dentin-like structures. Our findings demonstrate that the KN-17-loaded hydrogel can promote the regeneration of the pulp-dentin complex for continued root development.


Assuntos
Hidrogéis , Células-Tronco Mesenquimais , Camundongos , Ratos , Humanos , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Peptídeos , Odontoblastos , Dentina , Polpa Dentária
5.
Bioinformatics ; 39(11)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37882750

RESUMO

MOTIVATION: Neoantigens, tumor-specific protein fragments, are invaluable in cancer immunotherapy due to their ability to serve as targets for the immune system. Computational prediction of these neoantigens from sequencing data often requires multiple algorithms and sophisticated workflows, which are currently restricted to specific types of variants, such as single-nucleotide variants or insertions/deletions. Nevertheless, other sources of neoantigens are often overlooked. RESULTS: We introduce ScanNeo2 an improved and fully automated bioinformatics pipeline designed for high-throughput neoantigen prediction from raw sequencing data. Unlike its predecessor, ScanNeo2 integrates multiple sources of somatic variants, including canonical- and exitron-splicing, gene fusion events, and various somatic variants. Our benchmark results demonstrate that ScanNeo2 accurately identifies neoantigens, providing a comprehensive and more efficient solution for neoantigen prediction. AVAILABILITY AND IMPLEMENTATION: ScanNeo2 is freely available at https://github.com/ylab-hi/ScanNeo2/ and is accompanied by instruction and application data.


Assuntos
Neoplasias , Transcriptoma , Humanos , Antígenos de Neoplasias/genética , Software , Fluxo de Trabalho , Genômica , Neoplasias/genética
6.
ACS Omega ; 8(29): 25938-25950, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37521664

RESUMO

Although the preparation of coal-based carbon nanotubes (CNTs) has been realized in many studies, the relationship between carbon source structure of coal and CNT growth has not been studied in depth. In this study, we used lignite and KOH as raw material and catalyst and tuned lignite structure via hydrothermal modification to promote the formation of CNTs during catalytic pyrolysis. The main carbon source of CNTs was explored from the change of coal structure and pyrolysis characteristics. The results indicate that the CNT yield of lignite pyrolysis products is only 2.39%, but the CNT yield increases significantly after lignite was hydrothermally modified in a subcritical water-CO system. The graphitization degree, the order degree, and CNT content increase continuously with the increase in modification temperature, and C-M340 has the highest CNT content of 9.41%. Hydromodification promotes the rearrangement of aromatic carbon structures to generate more condensed aromatic rings linked by short aliphatic chains and aromatic ether bonds. The variation of these structures correlates well with the formation of CNTs and leads to the change in the carbon source components released during coal pyrolysis. Compared to lignite, modified coal releases more aromatic compounds, especially polycyclic aromatic hydrocarbons with ≥3 rings and phenols during catalytic pyrolysis, which is conducive to the transformation into carbon clusters and provides carbon sources for CNT growth. In addition, modified coal releases a slightly more carbon-containing gas (CH4 and CO) than lignite, which has a limited effect on the growth of CNTs. This study provides a novel and efficient method for enhancing the growth of CNTs by a molecular tailoring strategy of coal.

7.
Syst Parasitol ; 100(5): 473-485, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37314635

RESUMO

With growing scale of intensive fish cultivation, the risk of parasite infection in commercial fish is increased. Precisely identifying and characterizing the parasites that infect the farmed fish is critical to understanding the dynamics of their communities. Here, two species of Myxobolus were identified in farmed yellow catfish Tachysurus fulvidraco (Richardson) in China. Myxobolus distalisensis n. sp. developed plasmodia in the gill filaments, with oval to elliptical myxospores measuring 11.3 ± 0.6 (10.4-12.6) × 8.1 ± 0.3 (7.5-8.6) × 5.5 ± 0.2 (5.2-5.8) µm. Two pyriform polar capsules of equal size were measured 5.3 ± 0.4 (4.5-6.3) × 2.7 ± 0.1 (2.3-3) µm. Myxobolus voremkhai (Akhmerov, 1960) Landsberg and Lom, 1991 developed plasmodia in the gill arch and had a myxospore morphology similar to the conspecific isolates described in previous studies. The consensus sequences of M. distalisensis was remarkably distinct from those deposited in the GenBank, with exception of whereas M. voremkhai showing 99.84% identity. The genetic data on both isolates differed considerably from each other, revealing only 86.96% molecular identity. Histologically, M. distalisensis resided in the filament cartilage, and the aggressive proliferation of the sporogenic stages led to lytic cartilage corrosion. In contrast, plasmodia of M. voremkhai grossly observed at the base of the gill filament were embedded by the connective tissue in the gills arch. Phylogenetically, both isolates were separately placed in different subclades, indicating difference in their evolutionary history. Besides, the taxon under the family Myxobolidae was demonstrated non-monophyletic origins, and parasite radiation largely followed their host affinity.


Assuntos
Peixes-Gato , Cnidários , Doenças dos Peixes , Myxobolus , Myxozoa , Doenças Parasitárias em Animais , Animais , Myxozoa/genética , Myxobolus/genética , Peixes-Gato/parasitologia , Doenças Parasitárias em Animais/parasitologia , Filogenia , Doenças dos Peixes/parasitologia , Especificidade da Espécie , Brânquias/parasitologia
8.
Cell Death Dis ; 14(5): 322, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173306

RESUMO

Protein arginine methyltransferase 2 (PRMT2) is involved in several biological processes via histone methylation and transcriptional regulation. Although PRMT2 has been reported to affect breast cancer and glioblastoma progression, its role in renal cell cancer (RCC) remains unclear. Here, we found that PRMT2 was upregulated in primary RCC and RCC cell lines. We demonstrated that PRMT2 overexpression promoted RCC cell proliferation and motility both in vitro and in vivo. Moreover, we revealed that PRMT2-mediated H3R8 asymmetric dimethylation (H3R8me2a) was enriched in the WNT5A promoter region and enhanced WNT5A transcriptional expression, leading to activation of Wnt signaling and malignant progression of RCC. Finally, we confirmed that high PRMT2 and WNT5A expression was strongly correlated with poor clinicopathological characteristics and poor overall survival in RCC patient tissues. Our findings indicate that PRMT2 and WNT5A may be promising predictive diagnostic biomarkers for RCC metastasis. Our study also suggests that PRMT2 is a novel therapeutic target in patients with RCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Peptídeos e Proteínas de Sinalização Intracelular , Carcinogênese/genética , Transformação Celular Neoplásica , Neoplasias Renais/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Wnt-5a/genética , Proteína-Arginina N-Metiltransferases/genética
9.
Inorg Chem ; 62(23): 9005-9013, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37252689

RESUMO

Manipulating the interfacial/surface structure of ligand-stabilized atomically precise metal nanoclusters (NCs) is one of the central tasks in nanoscience because surface motifs are directly related to key properties of nanomaterials. Although great progress has been made in engineering the surface of gold and silver nanoclusters, parallel studies on lighter copper analogues hitherto remain unexplored. In this work, we report the design, synthesis, and structure of a new class of copper nanoclusters featuring virtually identical kernels but different surface motifs. The four Cu29 nanoclusters share the same Cu13 kernel with unprecedented anticuboctahedral architecture. Finely modulating synthetic parameters endows the Cu13 core with diverse surface structures, thus affording the Cu29 series with labile surface coatings. More interestingly, the slight surface modification results in distinct optical and catalytic properties of the cluster compounds, highlighting the importance of the surface structure in shaping the behaviors of copper nanomolecules. This work not only exemplifies the efficiency of surface engineering for controlling properties of well-defined copper nanoclusters but also provides a new family of Cu materials with a clear molecular structure and controlled surface motifs that hold great promise in studying structure-property relationships.

10.
RSC Adv ; 12(35): 22869-22880, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36105951

RESUMO

Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported so far. This review summarizes the synthetic strategies, synthetic routes and reaction processes of domperidone in detail. Domperidone can be synthesized from the coupling reaction of two benzimidazolone derivatives (intermediates 1 and 2). Intermediate 1 can be prepared by two synthetic routes: the cyclization of o-phenylenediamine with carbonyl reagents followed by coupling with 1,3-dihalopropane, and the coupling reaction of o-halo or o-amino substituted nitrobenzene with 1,3-disubstituted propane followed by reduction and cyclization. The latter route avoids the production of di-substituted by-products and has higher reaction selectivity. Intermediate 2 is synthesized by coupling substituted nitrobenzene with 4-aminopiperidine followed by reduction and cyclization, which is similar to the synthetic route of intermediate 1. Understanding the advantages and drawbacks of these synthetic methodologies would provide insights for the development of new strategies to prepare domperidone. Moreover, the methods used to synthesize domperidone can provide alternative approaches in the preparation of drugs or compounds with similar structure.

11.
Mar Drugs ; 20(5)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35621942

RESUMO

Myxozoa is a speciose group of endoparasitic cnidarians that can cause severe ecological and economic effects. Their cnidarian affinity is affirmed by genetic relatedness and the presence of nematocysts, historically called "polar capsules". Previous studies have revealed the presence of toxin-like proteins in myxozoans; however, the diversity and evolution of venom in Myxozoa are not fully understood. Here, we performed a comparative analysis using the newly sequenced transcriptomes of five Myxobolidae species as well as some public datasets. Toxin mining revealed that myxozoans have lost most of their toxin families, while most species retained Kunitz, M12B, and CRISP, which may play a role in endoparasitism. The venom composition of Endocnidozoa (Myxozoa + Polypodium) differs from that of free-living cnidarians and may be influenced by ecological and environmental factors. Phylogenetic analyses showed that toxin families of myxozoans and free-living cnidarians were clustered into different clades. Selection analyses showed that purifying selection was the dominant evolutionary pressure in toxins, while they were still influenced by episodic adaptive selection. This suggests that the potency or specificity of a particular toxin or species might increase. Overall, our findings provide a more comprehensive framework for understanding the diversity and evolution of Myxozoa venoms.


Assuntos
Hidrozoários , Myxozoa , Toxinas Biológicas , Animais , Myxozoa/genética , Filogenia , Proteínas , Transcriptoma/genética
12.
J Orthop Surg Res ; 17(1): 285, 2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35597957

RESUMO

BACKGROUND: The aim of this study is to compare the clinical and biomechanical outcome of INFIX plus single with two sacroiliac screw fixation for unstable pelvic fractures of Type C. METHODS: Sixteen cadavers were randomly subjected to INFIX plus single or double sacroiliac screw fixations and then mounted onto the ElectroForce loading machine under different vertical loads. To investigate the clinical outcomes of the two techniques, nineteen patients were retrospectively analyzed. The main outcome measures were postoperative radiographic reduction grading (using the Tornetta and Matta grading system), functional outcome (using the Majeed scoring system), and incidence of complications. RESULTS: In the biomechanical study, INFIX plus double sacroiliac screw fixation showed better biomechanical stability than fixation with a single sacroiliac screw (p < 0.05). In our clinical case series, all 19 patients had bony union 6 months after the operation. INFIX plus double sacroiliac screw fixation also demonstrated a better functional outcome and a higher radiographic satisfactory rate than INFIX plus single sacroiliac screw fixation (79.25 ± 5.47; 91.33 ± 4.97; p < 0.05), (77.78% vs. 60%; p = 0.05). One patient in INFIX plus single-screw fixation group had screw loosening at 6-month follow-up postoperatively. One case in each group suffered heterotopic ossification and the lateral femoral cutaneous nerve paralysis, and one patient suffered from infection. CONCLUSION: INFIX plus double sacroiliac screw fixation demonstrated more stability in cadaveric biomechanical analysis and better clinical outcomes than INFIX plus single sacroiliac screw fixation.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/lesões , Ossos Pélvicos/cirurgia , Estudos Retrospectivos
13.
Theranostics ; 12(3): 1286-1302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35154487

RESUMO

Rationale: Tumor energy metabolism has been a well-appreciated target of cancer therapy; however, the metabolism change of cancer cells between oxidative phosphorylation and glycolysis poses a challenge to the above. In this study, we constructed an innovative mitochondrion-targeted supramolecular "nano-boat" based on peptide self-assembly for tumor combined chemo-radiotherapy by simultaneously inhibiting the dual energy metabolism. Methods: A lipophilic self-assembled peptide and a positively charged cyclen were integrated to fabricate a brand new mitochondrion-targeted nano-platform for the first time. The indices of mitochondrial dysfunction including mitochondrial membrane potential, apoptosis proteins expression and ultrastructure change were evaluated using a JC-1 probe, western blotting and biological transmission electron microscopy, respectively. Energy metabolism assays were conducted on a Seahorse XF24 system by detecting the oxygen consumption rate and the glycolytic proton efflux rate. The radio-sensitization effect was investigated by colony formation, the comet assay, and γ-H2AX staining. Results: The supramolecular "nano-boat" could selectively kill cancer cells by much higher enrichment and reactive oxygen species generation than those in normal cells. In the cancer cells treated with the supramolecular "nano-boat", the dysfunctional morphological changes of the mitochondrial ultrastructure including swelling and pyknosis were evidently observed, and the endogenous mitochondrial apoptosis pathway was effectively triggered by abundant of cytochrome C leaking out. Concurrently, the dual metabolic pathways of glycolysis and oxidative phosphorylation were severely inhibited. More importantly, the supramolecular "nano-boat" displayed an excellent radio-sensitization effect with a sensitization enhancement ratio value as high as 2.58, and hence, in vivo efficiently combining radiotherapy yielded an enhanced chemo-radiotherapy effect. Conclusion: Our study demonstrated that the rationally designed peptide-based "nano-boat" could efficiently induce cancer cell apoptosis by the energy metabolism inhibition involving multiple pathways, which may provide the motivation for designing novel and universal mitochondria-targeted drug delivery systems for cancer therapy.


Assuntos
Metabolismo Energético , Mitocôndrias , Linhagem Celular Tumoral , Quimiorradioterapia , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Espécies Reativas de Oxigênio/metabolismo
14.
BMC Biol ; 20(1): 51, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35177085

RESUMO

BACKGROUND: Parasite evolution has been conceptualized as a process of genetic loss and simplification. Contrary to this model, there is evidence of expansion and conservation of gene families related to essential functions of parasitism in some parasite genomes, reminiscent of widespread mosaic evolution-where subregions of a genome have different rates of evolutionary change. We found evidence of mosaic genome evolution in the cnidarian Myxobolus honghuensis, a myxozoan parasite of fish, with extremely simple morphology. RESULTS: We compared M. honghuensis with other myxozoans and free-living cnidarians, and determined that it has a relatively larger myxozoan genome (206 Mb), which is less reduced and less compact due to gene retention, large introns, transposon insertion, but not polyploidy. Relative to other metazoans, the M. honghuensis genome is depleted of neural genes and has only the simplest animal immune components. Conversely, it has relatively more genes involved in stress resistance, tissue invasion, energy metabolism, and cellular processes compared to other myxozoans and free-living cnidarians. We postulate that the expansion of these gene families is the result of evolutionary adaptations to endoparasitism. M. honghuensis retains genes found in free-living Cnidaria, including a reduced nervous system, myogenic components, ANTP class Homeobox genes, and components of the Wnt and Hedgehog pathways. CONCLUSIONS: Our analyses suggest that the M. honghuensis genome evolved as a mosaic of conservative, divergent, depleted, and enhanced genes and pathways. These findings illustrate that myxozoans are not as genetically simple as previously regarded, and the evolution of some myxozoans is driven by both genomic streamlining and expansion.


Assuntos
Cnidários , Myxobolus , Parasitos , Animais , Cnidários/genética , Genoma , Proteínas Hedgehog , Filogenia
15.
Biology (Basel) ; 11(1)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35053089

RESUMO

Nematocysts are secretory organelles in cnidarians that play important roles in predation, defense, locomotion, and host invasion. However, the extent to which nematocysts contribute to adaptation and the mechanisms underlying nematocyst evolution are unclear. Here, we investigated the role of the nematocyst in cnidarian evolution based on eight nematocyst proteomes and 110 cnidarian transcriptomes/genomes. We detected extensive species-specific adaptive mutations in nematocyst proteins (NEMs) and evidence for decentralized evolution, in which most evolutionary events involved non-core NEMs, reflecting the rapid diversification of NEMs in cnidarians. Moreover, there was a 33-55 million year macroevolutionary lag between nematocyst evolution and the main phases of cnidarian diversification, suggesting that the nematocyst can act as a driving force in evolution. Quantitative analysis revealed an excess of adaptive changes in NEMs and enrichment for positively selected conserved NEMs. Together, these findings suggest that nematocysts may be key to the adaptive success of cnidarians and provide a reference for quantitative analyses of the roles of phenotypic novelties in adaptation.

16.
Anal Chem ; 94(4): 2236-2243, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35042329

RESUMO

The unique property of turning on their fluorescence after aggregation or assembly makes aggregation-induced emission luminogens (AIEgens) ideal luminescent molecules for the construction of self-assembled peptide-based nanoprobes. However, the characteristic highly twisted or propeller-shaped molecular conformation of AIEgens tends to prevent the assembly of AIEgen-peptides. Here, we show that (i) the distance between tetraphenylethene (TPE) and assembled peptides should not be too far (less than five glycines), otherwise the self-assembly of peptides cannot limit the intramolecular rotation of conjugated TPE and the luminous efficiency of TPE-peptide to alkaline phosphatase (ALP) will decrease; (ii) properly increasing the number of amino acids with self-assembly ability (three phenylalanines) can improve their ALP-responsive self-assembly and luminescence ability; (iii) the strategy of co-assembly with a non-AIEgen-capped self-assembled peptide is a simple and effective way to realize the efficient assembly and luminescence of AIEgen-peptides; and (iv) the hydrophilic and hydrophobic balance of the probe should always be considered in the construction of an efficient AIEgen-peptide probe. In addition, AIEgen-peptide probes show good selectivity and sensitivity for ALP detection both in vitro and in live bacteria. These insights illustrated here are crucial for guiding the design of AIEgen-conjugated supramolecular materials, especially for the construction of AIEgen-peptides, for enzymes detection, biomarker imaging, diseases therapy, and other biomedical fields.


Assuntos
Fosfatase Alcalina , Corantes Fluorescentes , Fluorescência , Corantes Fluorescentes/química , Luminescência , Peptídeos/química
17.
Cancer Sci ; 113(2): 733-743, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34859546

RESUMO

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half-life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake properties and stimulated drug release in the tumor micro-acidic environment. The PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and MMPs. Taken together, PM-nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Hidrogéis/uso terapêutico , Mifepristona/uso terapêutico , Paclitaxel/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Disponibilidade Biológica , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Portadores de Fármacos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrogéis/química , Hidrogéis/farmacologia , Camundongos , Mifepristona/química , Mifepristona/farmacologia , Nanoestruturas/uso terapêutico , Paclitaxel/química , Paclitaxel/farmacologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Clin Med ; 12(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36614970

RESUMO

PURPOSE: The objective of this study aimed to explore whether the original IVC regimen should be continued after the second TURBT or whether the IVC induction phase should be restarted from the beginning. METHODS: A retrospective analysis was performed on 137 patients who underwent a second TURBT at the Affiliated Hospital of Xuzhou Medical University between April 2014 and June 2022. Based on the pathological findings, patients were divided into two groups: group A patients, who did not have a residual tumor on pathological examination after the second TURBT; and group B patients, who had residual tumor. Recurrence was determined using cystoscopy and imaging every three months. The endpoint was recurrence-free survival. RESULT: In the entire cohort, there was a statistically significant difference in the RFS between patients in the two IVC regimens (p = 0.029). The RFS of patients in group B1 was significantly lower than that of patients in group B2 (p = 0.009). There was no significant difference in RFS between the subgroups A1 and A2 (p = 0.560). Multivariate Cox regression analysis confirmed that the IVC regimen after a second TURBT (p = 0.012) and T stage after a second TURBT (p = 0.005) were both independent predictors for patient RFS. CONCLUSION: If the pathological findings of the second TURBT specimen is benign, patients can continue their previous treatment regimen without restarting an IVC induction phase. Unnecessary IVC can be avoided in these patients. In contrast, for patients with residual tumors in the second TURBT specimen, the need to restart the IVC induction phase should be emphasized to improve patient prognosis.

19.
ACS Omega ; 6(32): 21160-21168, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34423224

RESUMO

The impacts of FeS catalysts on the hydromodification and structural evolution of lignite were investigated using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and X-ray photoelectron spectroscopy. The results indicate that the caking property of lignite can be significantly improved in the presence of the FeS catalyst. When 6.0 wt % FeS was added, the maximum caking index (G RI) of modified coal reached 95. During the hydromodification, FeS has little effect on the intrinsic water gas shift reaction, but it can increase the CO conversion by promoting the decomposition and hydrogenation of coal so that more active hydrogen is generated and introduced into modified coal. FeS is conducive to the rupture of distal aliphatic groups in the extractible solutes, which promotes the entrance of hydrogen into the aromatic nucleus (Har) and α positions (Hα) of asphaltenes and ß positions (Hß) of preasphaltenes. After the catalytic hydromodification, the longer side chains or bridge bonds break and are hydrogenated to form the aliphatic structures with a shorter chain or a higher branched degree. Meanwhile, more oxygen-containing functional groups were removed along with the reduction of volatiles in the modified coal. The synergistic effect of FeS on these factors is favorable for the generation of plastic materials, which contributes to the development of the caking property of lignite.

20.
Microb Pathog ; 153: 104772, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33529735

RESUMO

The myxozoan parasite Myxobolus xiantaoensis is a fin pathogen of commercially important yellow catfish Tachysurus fulvidraco Richardson, 1846, in the freshwater ponds of China. In the present work, four geographical isolates of M. xiantaoensis were sampled from the fins of yellow catfish. It was found that the spores of four isolates exhibited few markable differences in morphometrics. The small subunit ribosomal DNA (SSU rDNA) sequences of four isolates were conspecific to the SSU rDNA sequence of M. xiantaoensis. No genetic level variation was observed, even in the characteristically more variable internal transcribed spacer (ITS) region. This absence of variability suggests high gene flow as a result of panmixia in the parasitic populations. ITS phylogeny placed four isolates of M. xiantaoensis in a clade together with myxozoans species infecting Siluriformes. The M. xiantaoensis infection inflicted severe hemorrhages on epidermis of ray-fins, which grew into inflammatory epithelial hyperplasia and lytic cartilage signs. The histochemical analysis of infected fins biopsies is characterized by damage of collagen components of cartilage, resulting in weakness, breaks, and missing fin rays. These tissue sections also had a remarkable inflammatory response around the fin cartilage, with the absence of mature spores and chondrocytes. These results indicate that the fin cartilage damage appeared before the development of tissue inflammation and the parasitic infestation of the fins. The present four geographical isolates of M. xiantaoensis were identified by a holistic approach of species characterization based on biological, morphological, and molecular evidence. These four isolates showed some morphological and genetic variations but within the intraspecific range.


Assuntos
Peixes-Gato , Doenças dos Peixes , Myxobolus , Doenças Parasitárias em Animais , Animais , China , Brânquias , Myxobolus/genética , Filogenia
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