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1.
FASEB J ; 38(2): e23406, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38193601

RESUMO

Cancer-associated fibroblast (CAF) has emerged as a key contributor to the remodeling of tumor microenvironment through the expression and secretion of extracellular matrix (ECM) proteins, thereby promoting carcinogenesis. However, the precise contribution of ECM proteins from CAFs to gastric carcinogenesis remains poorly understood. In this study, we find that matrilin-3 (MATN3), an upregulated ECM protein associated with poorer prognosis in gastric cancer patients, originates from CAFs in gastric cancer tissues. Ectopic expression of MATN3 in CAFs significantly promotes the invasion of gastric cancer cells, which can be attenuated by neutralizing MATN3 with its antibody. Notably, a portion of MATN3 protein is found to form puncta in gastric cancer tissues ECM. MATN3 undergoes phase separation, which is mediated by its low complexity (LC) and coiled-coil (CC) domains. Moreover, overexpression of MATN3 deleted with either LC or CC in CAFs is unable to promote the invasion of gastric cancer cells, suggesting that LC or CC domain is required for the effect of CAF-secreted MATN3 in gastric cancer cell invasion. Additionally, orthotopic co-injection of gastric cancer cells and CAFs expressing MATN3, but not its ΔLC and ΔCC mutants, leads to enhanced gastric cancer cell invasion in mouse models. Collectively, our works suggest that MATN3 is secreted by CAFs and undergoes phase separation, which promotes gastric cancer invasion.


Assuntos
Fibroblastos Associados a Câncer , Proteínas Matrilinas , Neoplasias Gástricas , Animais , Humanos , Camundongos , Carcinogênese , Proteínas Matrilinas/genética , Invasividade Neoplásica , Separação de Fases , Neoplasias Gástricas/genética , Microambiente Tumoral
2.
Acta Haematol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527425

RESUMO

Introduction Multiple myeloma (MM) is a malignant proliferative disease of plasma cells. Abnormally cloned plasma cells secrete large amounts of monoclonal immunoglobulins in the bone marrow of MM patients. Serum urea nitrogen (sUN) is a byproduct of protein metabolism, and its effect on MM patients' prognoses remains unknown. Therefore, we analysed MM patients' clinical data to explore the role of sUN and serum urea nitrogen/serum albumin (sUAR) in the baseline tumor load and MM prognosis of MM patients. Methods We downloaded the clinical data of 762 MM patients from the MMRF database. After excluding those without baseline sUN, 452 patients were finally included in the study. Smoothed curve fitting, threshold analysis, Tamhane's T2 test, multivariate adjusted Cox regression analysis, Kaplan‒Meier (K-M) curves, and receiver operating characteristic (ROC) analysis were applied in the study. Results There were 452 newly diagnosed MM patients included in this study. In most patient groups, sUN and sUAR were positively linked with ß2-microglobulin (ß2-MG) and lactic dehydrogenase (LDH) according to smoothing curve fitting and threshold analysis. The higher the ISS stage, the greater the values of sUN and sUAR. Furthermore, smoothed curve fitting and threshold analysis showed that sUN was correlated with OS, although sUAR had a stronger correlation with OS and could be applied to a broader group. The results of a multivariate adjusted Cox regression analysis demonstrated that sUN and sUAR were independent prognostic factors for OS. The K-M curve confirmed the correlation between higher sUN and sUAR levels and worse OS. ß2-MG and LDH are generally recognized prognostic factors of OS. ROC analysis revealed that sUN might boost ß2-MG and LDH's predictive value and sUAR had a higher predictive value. Conclusion This retrospective study based on the MMRF database showed that high sUN and sUAR levels were positively associated with ß2-MG, LDH, and ISS staging, and sUAR exhibited a stronger correlation with OS than sUN alone.

3.
Angew Chem Int Ed Engl ; 62(26): e202303327, 2023 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-37119055

RESUMO

Electrochemical conversion of nitrate (NO3 - ) into ammonia (NH3 ) represents a potential way for achieving carbon-free NH3 production while balancing the nitrogen cycle. Herein we report a high-performance Cu nanosheets catalyst which delivers a NH3 partial current density of 665 mA cm-2 and NH3 yield rate of 1.41 mmol h-1 cm-2 in a flow cell at -0.59 V vs. reversible hydrogen electrode. The catalyst showed a high stability for 700 h with NH3 Faradaic efficiency of ≈88 % at 365 mA cm-2 . In situ spectroscopy results verify that Cu nanosheets are in situ derived from the as-prepared CuO nanosheets under electrochemical NO3 - reduction reaction conditions. Electrochemical measurements and density functional theory calculations indicate that the high performance is attributed to the tandem interaction of Cu(100) and Cu(111) facets. The NO2 - generated on the Cu(100) facets is subsequently hydrogenated on the Cu(111) facets, thus the tandem catalysis promotes the crucial hydrogenation of *NO to *NOH for NH3 production.


Assuntos
Amônia , Nitratos , Catálise , Eletrodos , Hidrogenação
4.
Small ; 18(39): e2203680, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36031402

RESUMO

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed. Taking advantage of remote accessibility of magnetic field together with the superparamagnetic hydrogels, a temporal engineered M1 to M2 transition course preserving the essential role of M1 at the early stage of tissue healing, as well as enhancing the prohealing effect of M2 at the middle/late stages is established via delayed MF switch. Such precise timing of macrophage polarization matching the regenerative process of injured tissue eventually leads to optimized immunomodulatory bone healing in vivo. Overall, this study offers a remotely time-scheduled approach for macrophage polarization, which enables precise manipulation of inflammation progression during tissue healing.


Assuntos
Regeneração Óssea , Macrófagos , Colágeno/metabolismo , Humanos , Hidrogéis/farmacologia , Imunomodulação , Inflamação/metabolismo , Macrófagos/metabolismo , Fenótipo
5.
BMC Pediatr ; 22(1): 528, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064339

RESUMO

BACKGROUND: Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene. CASE PRESENTATION: Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein. CONCLUSION: The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.


Assuntos
Braquidactilia , Sindactilia , Braquidactilia/diagnóstico , Braquidactilia/genética , Ossos do Carpo/anormalidades , Feminino , Deformidades Congênitas do Pé , Deformidades Congênitas da Mão , Humanos , Linhagem , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo , Estribo/anormalidades , Sinostose , Ossos do Tarso/anormalidades
6.
Am J Dent ; 35(2): 146-151, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35798710

RESUMO

PURPOSE: To evaluate the plaque removal efficacy of a compacted dual-head power toothbrush (DH) in comparison with a single-head power toothbrush (SH). METHODS: 24 healthy university students were included in this split-mouth and single-center clinical trial. The DH and SH were randomly assigned to brush the left/right half mouth in the first visit. Testing time points were 30 and 60 seconds. Additionally, 15 and 45 seconds were set for the DH period. The overall, buccal, lingual, gingival marginal, and proximal plaque scores at different time points were recorded and determined by Rustogi Modification of the Navy Plaque Index. To avoid the influence of the right handedness, subjects were brushed in the second visit after 4 weeks, and the SH and the DH were assigned to the right/left half mouth in an opposite period to that of the first visit. RESULTS: 21 participants completed this study. Overall plaque score reductions of the SH and DH were 29% and 59% (P< 0.05) at 30 seconds, and the reductions were 47% and 77% respectively (P< 0.05) at 60 seconds. Using the DH for 45 seconds reduced significantly more overall, buccal, lingual, and gingival marginal plaque than that of using SH for 60 seconds (P< 0.05). The SH reduced plaque scores significantly less in the right and lower dentitions than left and upper dentitions respectively, while DH reduced comparable plaque scores between these dentitions. The DH is more effective in removing overall, buccal, lingual, gingival marginal, and proximal plaque in healthy university students than the SH, meanwhile DH showed comparable overall plaque reduction rates between different regions of the dentitions. CLINICAL SIGNIFICANCE: This compact dual-head power toothbrush provides a new option to carry out daily plaque control effectively.


Assuntos
Placa Dentária , Gengivite , Índice de Placa Dentária , Desenho de Equipamento , Humanos , Método Simples-Cego , Escovação Dentária , Resultado do Tratamento
7.
Fish Physiol Biochem ; 48(3): 805-815, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35416634

RESUMO

In this study, an efficient estradiol-17ß (E2)-induced feminization method was established based on the timing of early gonadal differentiation in Largemouth bass (Micropterus salmoides). Histological section results showed that from 20 days post-hatch (dph) to 30 dph, the germ cells gradually differentiated into oogonium and spermatic deferent, respectively. Moreover, female-biased genes Foxl2 and Cyp19a1a were up-regulated to the first peak at 20 dph, while the male-biased genes Dmrt1 were up-regulated to the first peak at 30 dph. These results indicated that the timing of early gonadal differentiation in Largemouth bass was between 20 and 30 dph. Therefore, 15 dph Largemouth bass with a body length of 15.10 ± 0.09 mm were chosen, and four E2-treated diets were set as 0 (E0, control), 50 mg/kg E2 (E50), 100 mg/kg E2 (E100), and 200 mg/kg E2 (E200). After feeding with E2-treated diets for 60 days, female ratios were 55%, 100%, 100%, and 100% in E0, E50, E100, and E200 groups, respectively. No intersex fish were observed in all the groups. However, 30% of females in the E200 group possessed thinner ovaries, with smaller ovary cavity structures and a decreased number of primary oocyte cells than those in other groups. Besides, the Largemouth bass in the E0 group grew more than those in E50, E100, and E200 groups during the E2 treatments period (P < 0.05). In conclusion, our study suggested that 50-100 mg/kg E2-treated diets could effectively induce the feminization of 15 dph Largemouth bass within 60 days duration time, which provided valuable information for the breeding of the all-male Largemouth bass population.


Assuntos
Bass , Animais , Bass/genética , Estradiol/farmacologia , Feminino , Feminização , Gônadas , Masculino , Diferenciação Sexual
8.
Angew Chem Int Ed Engl ; 59(12): 4814-4821, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-31944516

RESUMO

The electrochemical CO2 reduction reaction (CO2 RR) to give C1 (formate and CO) products is one of the most techno-economically achievable strategies for alleviating CO2 emissions. Now, it is demonstrated that the SnOx shell in Sn2.7 Cu catalyst with a hierarchical Sn-Cu core can be reconstructed in situ under cathodic potentials of CO2 RR. The resulting Sn2.7 Cu catalyst achieves a high current density of 406.7±14.4 mA cm-2 with C1 Faradaic efficiency of 98.0±0.9 % at -0.70 V vs. RHE, and remains stable at 243.1±19.2 mA cm-2 with a C1 Faradaic efficiency of 99.0±0.5 % for 40 h at -0.55 V vs. RHE. DFT calculations indicate that the reconstructed Sn/SnOx interface facilitates formic acid production by optimizing binding of the reaction intermediate HCOO* while promotes Faradaic efficiency of C1 products by suppressing the competitive hydrogen evolution reaction, resulting in high Faradaic efficiency, current density, and stability of CO2 RR at low overpotentials.

9.
World J Microbiol Biotechnol ; 35(12): 185, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31728760

RESUMO

Glutathione (GSH) and S-adenosyl methionine (SAM) have been applied as liver-protective factors to prevent and treat many different liver damages and diseases. Due to their low stability and short half-life, oral administration of GSH or SAM might be replaced by continuous supplying through living lactic bacteria in yogurt. In this study, Lactococcus lactis was engineered via synthetic biology strategies to produce these two important molecules. The bi-functional GSH synthase gene (gshF) and SAM synthase gene (metK) were transformed into food-grade L. lactis together with an adhesion factor gene (cwaA). The highest accumulation of SAM (9.0 mg/L) and GSH (17.3 mg/L) was achieved after 17 h cultivation of the recombinant L. lactis. Meanwhile, the autoaggregation and hydrophobicity were also improved significantly, which suggested that this engineered L. lactis might have an increased colonization-prone ability in human GI. Our studies demonstrated one potential route to self-produce and deliver the liver-healthy factors within living probiotic bacteria.


Assuntos
Glutationa/metabolismo , Lactococcus lactis/metabolismo , Engenharia Metabólica/métodos , S-Adenosilmetionina/metabolismo , Adesinas Bacterianas/genética , Vias Biossintéticas , Fermentação , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos/genética , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Lactococcus lactis/enzimologia , Lactococcus lactis/genética , Lactococcus lactis/crescimento & desenvolvimento , Metionina Adenosiltransferase/genética , Nisina/metabolismo , Probióticos
10.
Sensors (Basel) ; 18(9)2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208646

RESUMO

With the continuous development of the convolutional neural network (CNN) concept and other deep learning technologies, target recognition in Synthetic Aperture Radar (SAR) images has entered a new stage. At present, shallow CNNs with simple structure are mostly applied in SAR image target recognition, even though their feature extraction ability is limited to a large extent. What's more, research on improving SAR image target recognition efficiency and imbalanced data processing is relatively scarce. Thus, a lightweight CNN model for target recognition in SAR image is designed in this paper. First, based on visual attention mechanism, the channel attention by-pass and spatial attention by-pass are introduced to the network to enhance the feature extraction ability. Then, the depthwise separable convolution is used to replace the standard convolution to reduce the computation cost and heighten the recognition efficiency. Finally, a new weighted distance measure loss function is introduced to weaken the adverse effect of data imbalance on the recognition accuracy of minority class. A series of recognition experiments based on two open data sets of MSTAR and OpenSARShip are implemented. Experimental results show that compared with four advanced networks recently proposed, our network can greatly diminish the model size and iteration time while guaranteeing the recognition accuracy, and it can effectively alleviate the adverse effects of data imbalance on recognition results.

11.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38887599

RESUMO

Tobacco consumption in China remains the primary cause of preventable mortality, with Shanghai being particularly affected by issues related to secondhand smoke exposure. This study explores the role of the public service hotline 12345, a grassroots initiative in Shanghai, in capturing public sentiment and assessing the effectiveness of anti-smoking regulations. Our research aims to accurately and deeply understand the implementation and feedback of smoking control policies: by identifying high-frequency points and prominent issues in smoking control work based on the smoking control work order data received by the health hotline 12320. The results of this study will assist government enforcement agencies in improving smoking monitoring and clarify the direction for improving smoking control measures. Text-mining techniques were employed to analyze a dataset comprising 78011 call sheets, all related to tobacco control and collected from the hotline between 1 January 2015 and 31 December 2019. This methodological approach aims to uncover prevalent themes and sentiments in the public discourse on smoking and its regulation, as reflected in the hotline interactions. Our study identified hotspots and the issues of greatest concern to citizens. Additionally, it provided recommendations to enforcement agencies to enhance their capabilities, optimize the allocation of human resources for smoking control monitoring, reduce enforcement costs and support for anti-smoking campaigns, thereby contributing to more effective tobacco control policies in the region.

12.
Food Res Int ; 190: 114629, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945621

RESUMO

This study aims to investigate the effects of ultrasound coupled with alkali cycling on the structural properties, digestion characteristics, biological activity, and peptide profiling of flaxseed protein isolates (FPI). The digestibility of FPI obtained by ultrasound coupled with pH 10/12 cycling (UFPI-10/12) (74.56 % and 79.12 %) was significantly higher than that of native FPI (64.40 %), and UFPI-10 showed higher hydrolysis degree (35.76 %) than FPI (30.65 %) after intestinal digestion. The combined treatment induced transition from α-helix to ß-sheet with an orderly structure. Large FPI aggregates broke down into small-sized FPI particles, which induced the increase of specific surface area of particles. This might expose more cutting sites and contact area with enzymes. Furthermore, UFPI-10 showed high antioxidant activity (29.18 %) and lipid-lowering activity (70.52 %). Peptide profiling revealed that UFPI-10 exhibited a higher proportion of 300-600 Da peptides and significantly higher abundance of antioxidant peptides than native FPI, which might promote its antioxidant activity. Those results suggest that the combined treatment is a promising modification method to improve the digestion characteristics and biological activity of FPI. This work provides new ideas for widespread use of FPI as an active stabilizer in food systems.


Assuntos
Álcalis , Antioxidantes , Digestão , Linho , Peptídeos , Proteínas de Plantas , Linho/química , Peptídeos/metabolismo , Peptídeos/química , Antioxidantes/química , Antioxidantes/análise , Proteínas de Plantas/metabolismo , Álcalis/química , Concentração de Íons de Hidrogênio , Hidrólise , Sementes/química , Manipulação de Alimentos/métodos , Ondas Ultrassônicas
13.
Int J Biol Macromol ; 273(Pt 2): 133139, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38878929

RESUMO

The microencapsulation of polysaturated fatty acids by spray drying remains a challenge due to their susceptibility to oxidation. In this work, antioxidant Pickering emulsions were attempted as feeds to produce oxidation stable tuna oil microcapsules. The results indicated that the association between chitosan (CS) and ovalbumin (OVA) was a feasible way to fabricate antioxidant and wettable complexes and a high CS percentage favored these properties. The particles could yield tuna oil Pickering emulsions with enhanced oxidation stability through high-pressure homogenization, which were successfully spray dried to produce microcapsules with surface oil content of 8.84 % and microencapsulation efficiency of 76.65 %. The microcapsules exhibited significantly improved oxidation stability and their optimum peroxide values after storage at 50 °C, 85 % relative humidity, or natural light for 15 d were 48.67 %, 60.07 %, and 39.69 % respectively lower than the powder derived from the OVA-stabilized emulsion. Hence, Pickering emulsions stabilized by the CS/OVA polyelectrolyte complexes are potential in the production of oxidation stable polyunsaturated fatty acid microcapsules by spray drying.


Assuntos
Cápsulas , Quitosana , Emulsões , Ovalbumina , Oxirredução , Secagem por Atomização , Atum , Quitosana/química , Emulsões/química , Ovalbumina/química , Animais , Óleos de Peixe/química , Polieletrólitos/química , Antioxidantes/química , Tamanho da Partícula
14.
Protein Cell ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801297

RESUMO

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for successful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mammalian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinucleation and midbody disorganization. Using iTRAQ-based quantitative proteomic analysis, we find that RCC2 levels are decreased in NudCL2 knockout (KO) cells. Moreover, Hsp90 forms a complex with NudCL2 to stabilize RCC2, which is essential for cytokinesis. RCC2 depletion mirrors phenotypes observed in NudCL2-downregulated cells. Importantly, ectopic expression of RCC2 rescues the cytokinesis defects induced by NudCL2 deletion, but not vice versa. Together, our data reveal the significance of the NudCL2/Hsp90/RCC2 pathway in cytokinesis at the midbody.

15.
Food Res Int ; 175: 113673, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38129022

RESUMO

Enrichment of plant proteins with functionality is of great importance for expanding their application in food formulations. This study proposed an innovation to co-enrich soy protein and flaxseed protein to act as efficient interfacial stabilizers for generating foams and emulsions. The structure, interfacial properties, and functionalities of the soy protein-flaxseed protein natural nanoparticles (SFNPs) obtained by alkali extraction-isoelectric precipitation (AE) and salt extraction-dialysis (SE) methods were investigated. Overall, the foamability of AE-SFNPs (194.67 %) was 1.45-fold that of SE-SFNPs, due to their more flexible structure, smaller particle size, and suitable surface wettability, promoting diffusion and adsorption at the air-water interface. AE-SFNPs showed higher emulsion stability (140.89 min), probably because the adsorbed AE-SFNPs with smaller size displayed soft particle-like properties and stronger interfacial flexibility, and therefore could densely and evenly arrange at the interface, facilitating the formation of a stiff and solid-like interfacial layer, beneficial for more stable emulsion formation. The findings may innovatively expand the applications of SFNPs as food ingredients.


Assuntos
Linho , Proteínas de Soja , Proteínas de Soja/química , Emulsões/química , Diálise Renal , Proteínas de Plantas/química
16.
ACS Chem Biol ; 19(7): 1440-1446, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38901034

RESUMO

Peptide-bile acid hybrids offer promising drug candidates due to enhanced pharmacological properties, such as improved protease resistance and oral bioavailability. However, it remains unknown whether bile acids can be incorporated into peptide chains by the ribosome to produce a peptide-bile acid hybrid macrocyclic peptide library for target-based de novo screening. In this study, we achieved the ribosomal incorporation of lithocholic acid (LCA)-d-tyrosine into peptide chains. This led to the construction of a peptide-LCA hybrid macrocyclic peptide library, which enabled the identification of peptides TP-2C-4L3 (targeting Trop2) and EP-2C-4L5 (targeting EphA2) with strong binding affinities. Notably, LCA was found to directly participate in binding to EphA2 and confer on the peptides improved stability and resistance to proteases. Cell staining experiments confirmed the high specificity of the peptides for targeting Trop2 and EphA2. This study highlights the benefits of LCA in peptides and paves the way for de novo discovery of stable peptide-LCA hybrid drugs.


Assuntos
Ácido Litocólico , Biblioteca de Peptídeos , Peptídeos , Ribossomos , Ácido Litocólico/química , Ácido Litocólico/análogos & derivados , Ácido Litocólico/metabolismo , Ribossomos/metabolismo , Humanos , Peptídeos/química , Peptídeos/metabolismo , Receptor EphA2/metabolismo , Receptor EphA2/química , Descoberta de Drogas , Peptídeos Cíclicos/química , Peptídeos Cíclicos/metabolismo
17.
Front Cell Dev Biol ; 11: 1166916, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152280

RESUMO

Malignant melanoma (MM) is the most metastatic and aggressive form of skin cancer, and carries a high risk of death. Immune-checkpoint inhibitor therapy and molecular-targeted therapy can prolong the survival of patients with advanced MM significantly. However, the low response rate and inevitable drug resistance prevent further improvements in efficacy, which is closely related to the tumor microenvironment (TME). The TME refers to the tumor stroma, including fibroblasts, keratinocytes, immune cells, soluble molecules, and extracellular matrix (ECM). The dynamic interaction between the TME and tumor cells is very important for the growth, local invasion, and metastatic spread of tumor cells. A patient-derived organoid (PDO) model involves isolation of tumor tissue from patients with MM and culturing it in vitro in a three-dimensional pattern. Compared with traditional cultivation methods, the PDO model preserves the heterogeneity of the tissue structure of MM and demonstrates the interaction between MM cells and the TME. It can reproduce the characteristics of proliferation, migration, and invasion of MM cells, and better simulate the structural function of MM in vivo. This review explores the role of each TME component in development of the PDO model. This review will provide a reference for research on the drug screening and targeted treatment using PDOs, particularly for the immunotherapy of MM.

18.
ACS Biomater Sci Eng ; 9(5): 2483-2494, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37092608

RESUMO

Osteoimmunomodulation has been considered to play a key role in osteointegration of orthopedic biomaterials. However, regulation of the macrophage phenotype in vivo with a spatiotemporal controllable way still remains a challenge. In this study, we designed a novel magnetic-responsive mineralized collagen coating to exert remotely controlled magneto-mechanical stimulation on macrophages using an external magnetic field. The magneto-mechanical stimulation exhibited immunomodulatory capability to activate M2 macrophage polarization via triggering the integrin-related cascade pathway and suppressing the phosphorylation of JNK in the MAPK pathway. The optimized inflammatory microenvironment subsequently promoted the osteogenic differentiation of bone marrow-derived mesenchymal stem cells and the osteointegration in vivo. This work, therefore, provides a remote spatiotemporal controllable strategy to promote the osteointegration of orthopedic biomaterials via regulation of the osteoimmune microenvironment.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Macrófagos/metabolismo , Materiais Biocompatíveis , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular
19.
Sci Rep ; 13(1): 18461, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891233

RESUMO

Acceptance of artificial pelleted diets contributes to increasing the cultured areas and output of carnivorous fish. However, the mechanism of acceptance of artificial pelleted diets remains largely unknown. In this study, the easy acceptance of artificial pelleted diets (EAD) group and the not easy acceptance of artificial pelleted diets (NAD) group of Largemouth bass (Micropterus salmoides) were divided based on the ratios of stomach weight/body weight (SB) after 0.5 h feeding, which was bigger than 18% in the EAD group and ranged from 8 to 12% in the NAD group. Through transcriptome and proteome sequencing, a total of 2463 differentially expressed genes (DEGs) and 230 differentially expressed proteins (DEPs) were identified, respectively. Integrated analyses of transcriptome and proteome data revealed that 152 DEPs were matched with the corresponding DEGs (named co-DEGs-DEPs), and 54 co-DEGs-DEPs were enriched in 16 KEGG pathways, including the metabolic pathways, steroid biosynthesis, fatty acid biosynthesis, etc. Furthermore, 3 terpenoid backbone biosynthesis-related genes (Hmgcr, Hmgcs, and Fdps) in metabolic pathways, 10 steroid biosynthesis-related genes (Fdft1, Sqle, Lss, Cyp51a1, Tm7sf2, Nsdhl, Hsd17b7, Dhcr24, Sc5d, and Dhcr7), and 3 fatty acid biosynthesis-related genes (Acaca, Fasn, and Ascl) were all up-regulated in the EAD group, suggesting that the lipid metabolism pathway and steroid biosynthesis pathway play important roles in early food habit domestication in Largemouth bass. In addition, the detection results of randomly selected 15 DEGs and 15 DEPs indicated that both transcriptome and proteome results in the study were reliable. Our study provides useful information for further research on the mechanisms of food habit domestication in fish.


Assuntos
Bass , Transcriptoma , Animais , Bass/genética , Bass/metabolismo , Proteoma/metabolismo , Proteômica , Domesticação , NAD/metabolismo , Dieta , Comportamento Alimentar , Ácidos Graxos/metabolismo , Esteroides/metabolismo
20.
PeerJ ; 11: e14588, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643624

RESUMO

Background: The largemouth bass (Micropterus salmoides), an economically important freshwater fish species widely farmed in China, is traditionally cultured using a diet of forage fish. However, given the global decline in forage fish fisheries and increasing rates of waterbody pollution and disease outbreaks during traditional culturing, there is a growing trend of replacing forage fish with formulated feed in the largemouth bass breeding industry. The specific molecular mechanisms associated with such dietary transition in this fish are, nevertheless, poorly understood. Methods: To identify single nucleotide polymorphisms (SNPs) related to food habit domestication traits and growth traits in largemouth bass fry, we initially genotyped fry using eight candidate SNPs based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, with genetic parameters being determined using Popgen32 and Cervus 3.0. Subsequently, we assessed the associations between food habit domestication traits of largemouth bass fry and these SNPs using the Chi-square test or Fisher's exact test. Furthermore, we used a general linear model to assess the relationships between the growth traits of largemouth bass fry and these SNPs. The Pearson correlation coefficient between growth traits and the SNPs was also determined using bivariate correlation analysis in IBM SPSS Statistics 22. Finally, the phenotypic variation explained (PVE) by the SNPs was calculated by regression analysis in Microsoft Excel. Results: The genotyping results obtained based on PCR-RFLP analysis were consistent with those of direct sequencing. Five SNPs (SNP01, SNP02, SNP04, SNP05, and SNP06) were found to be significantly correlated with the food habit domestication traits of fry (P < 0.05); SNP01 (P = 0.0011) and SNP04 (P = 0.0055) particularly, had showed highly significant associations. With respect to growth traits, we detected significant correlations with the two SNPs (SNP01 and SNP07) (P < 0.05), with SNP01 being significantly correlated with body length, and height (P < 0.05), and SNP07 being significantly correlated with body height only (P < 0.05). Conclusions: Our findings indicated that the PCR-RFLP can be used as a low-cost genotyping method to identify SNPs related to food habit domestication and growth traits in largemouth bass, and that these trait-related SNPs might provide a molecular basis for the future breeding of new varieties of largemouth bass.


Assuntos
Bass , Animais , Bass/genética , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Domesticação , Reação em Cadeia da Polimerase
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