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1.
Hematology ; 29(1): 2339778, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38625693

RESUMO

OBJECTIVE: To establish an efficient nomogram model to predict short-term survival in ICU patients with aplastic anemia (AA). METHODS: The data of AA patients in the MIMIC-IV database were obtained and randomly assigned to the training set and testing set in a ratio of 7:3. Independent prognosis factors were identified through univariate and multivariate Cox regression analyses. The variance inflation factor was calculated to detect the correlation between variables. A nomogram model was built based on independent prognostic factors and risk scores for factors were generated. Model performance was tested using C-index, receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA) and Kaplan-Meier curve. RESULTS: A total of 1,963 AA patients were included. A nomogram model with 7 variables was built, including SAPS II, chronic pulmonary obstructive disease, body temperature, red cell distribution width, saturation of peripheral oxygen, age and mechanical ventilation. The C-indexes in the training set and testing set were 0.642 and 0.643 respectively, indicating certain accuracy of the model. ROC curve showed favorable classification performance of nomogram. The calibration curve reflected that its probabilistic prediction was reliable. DCA revealed good clinical practicability of the model. Moreover, the Kaplan-Meier curve showed that receiving mechanical ventilation could improve the survival status of AA patients in the short term but did not in the later period. CONCLUSION: The nomogram model of the short-term survival rate of AA patients was built based on clinical characteristics, and early mechanical ventilation could help improve the short-term survival rate of patients.


Assuntos
Anemia Aplástica , Humanos , Anemia Aplástica/diagnóstico , Anemia Aplástica/terapia , Nomogramas , Bases de Dados Factuais , Índices de Eritrócitos , Unidades de Terapia Intensiva
3.
Food Chem ; 449: 139216, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38604031

RESUMO

This study aimed to identify saltiness-enhancing peptides from yeast protein and elucidate their mechanisms by molecular docking. Yeast protein hydrolysates with optimal saltiness-enhancing effects were prepared under conditions determined using an orthogonal test. Ten saltiness-enhancing peptide candidates were screened using an integrated virtual screening strategy. Sensory evaluation demonstrated that these peptides exhibited diverse taste characteristics (detection thresholds: 0.13-0.50 mmol/L). Peptides NKF, LGLR, WDL, NMKF, FDSL and FDGK synergistically or additively enhanced the saltiness of a 0.30% NaCl solution. Molecular docking revealed that these peptides predominantly interacted with TMC4 by hydrogen bonding, with hydrophilic amino acids from both peptides and TMC4 playing a pivotal role in their binding. Furthermore, Leu217, Gln377, Glu378, Pro474 and Cys475 were postulated as the key binding sites of TMC4. These findings establish a robust theoretical foundation for salt reduction strategies in food and provide novel insights into the potential applications of yeast proteins.


Assuntos
Simulação de Acoplamento Molecular , Peptídeos , Paladar , Peptídeos/química , Peptídeos/metabolismo , Humanos , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/metabolismo , Cloreto de Sódio/química
4.
Food Res Int ; 182: 114139, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519171

RESUMO

The previously obtained chicken-derived umami peptides in the laboratory were evaluated for their saltiness-enhancing effect by sensory evaluation and S-curve, and the results revealed that peptides TPPKID, PKESEKPN, TEDWGR, LPLQDAH, NEFGYSNR, and LPLQD had significant saltiness-enhancing effects. In the binary solution system with salt, the ratio of the experimental detection threshold (129.17 mg/L) to the theoretical detection threshold (274.43 mg/L) of NEFGYSNR was 0.47, which had a synergistic saltiness-enhancing effect with salt. The model of transmembrane channel-like protein 4 (TMC4) channel protein was constructed by homology modeling, which had a 10-fold transmembrane structure and was well evaluated. Molecular docking and frontier molecular orbitals showed that the main active sites of TMC4 were Lys 471, Met 379, Cys 475, Gln 377, and Pro 380, and the main active sites of NEFGYSNR were Tyr, Ser and Asn. This study may provide a theoretical reference for low-sodium diets.


Assuntos
Galinhas , Peptídeos , Animais , Simulação de Acoplamento Molecular , Peptídeos/química , Proteínas , Cloreto de Sódio na Dieta
5.
Food Res Int ; 178: 113908, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309861

RESUMO

Yeast extract (YE) is derived from the soluble component in yeast cells, which is rich in peptides and has been used as a sweet-enhancing agent. It has the potential to be utilized to produce natural sweet-flavored peptides or sweet-enhancing peptides. To study the synergistic effect and mechanism of sweetness-enhancing peptides derived from YE, ultrafiltration fraction with molecular weight less than 1 kDa was screened according to sensory analysis, which showed a synergistic sweetening effect in stevioside and mogroside solution. Twenty potential taste peptides were identified from the screened fractions, among which EV, AM, AVDNIPVGPN and VDNIPVGPN showed sweetness-enhancing effects on both stevioside and mogroside. The sweetener-receptor-peptide complex was constructed to investigate the interaction of stevioside and mogroside to taste receptor type 1 member 2 accompanied by these peptides. The results of the molecular docking indicated that new hydrophobic interactions (Leu 279, Pro 308, Val 309, etc.) and hydrogen bonds (Ser 40, Ala 43, Asp 278, etc.) were formed between sweeteners and active sites in the venus flytrap domain. In conclusion, the presence of sweetness-enhancing peptides from YE improved the binding stability of sweeteners and receptors by increasing the binding interaction, especially the hydrophobic interactions, which contribute to the synergistic effect of sweetness-enhancing peptides.


Assuntos
Diterpenos do Tipo Caurano , Glucosídeos , Edulcorantes , Simulação de Acoplamento Molecular , Edulcorantes/análise , Diterpenos do Tipo Caurano/análise , Peptídeos/farmacologia
6.
J Exp Clin Cancer Res ; 43(1): 44, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326863

RESUMO

BACKGROUND: m6A modification is currently recognized as a major driver of RNA function that maintains cancer cell homeostasis. Long non-coding (Lnc) RNAs control cell proliferation and play an important role in the occurrence and progression of colorectal cancer (CRC). ZCCHC4 is a newly discovered m6A methyltransferase whose role and mechanism in tumors have not yet been elucidated. METHODS: The EpiQuik m6A RNA methylation kit was used to detect the level of total RNA m6A in six types of digestive tract tumors. The Kaplan-Meier method and receiver operating characteristic curve were used to evaluate the prognostic and diagnostic value of the newly discovered m6A methyltransferase, ZCCHC4, in CRC. The effects on CRC growth in vitro and in vivo were studied using gain- and loss-of-function experiments. The epigenetic mechanisms underlying ZCCHC4 upregulation in CRC were studied using RIP, MeRIP-seq, RNA pull-down, and animal experiments. RESULTS: We reported that the ZCCHC4-LncRNAGHRLOS-KDM5D axis regulates the growth of CRC in vitro and in vivo. We found that ZCCHC4 was upregulated in primary CRC samples and could predict adverse clinical outcomes in patients with CRC. Mechanistically, ZCCHC4 downregulated LncRNAGHRLOS to promote CRC tumorigenesis. As a downstream molecule of LncRNAGHRLOS, KDM5D directly controls CRC cell proliferation, migration, and invasion. CONCLUSION: This study suggests that the ZCCHC4 axis contributes to the tumorigenesis and progression of CRC and that ZCCHC4 may be a potential biomarker for this malignancy.


Assuntos
Adenina , Neoplasias Colorretais , RNA Longo não Codificante , Animais , Humanos , Adenina/análogos & derivados , Carcinogênese/genética , Linhagem Celular Tumoral , Transformação Celular Neoplásica/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Epigênese Genética , Histona Desmetilases/genética , Metiltransferases/metabolismo , Antígenos de Histocompatibilidade Menor , RNA , RNA Longo não Codificante/genética , tRNA Metiltransferases/genética , tRNA Metiltransferases/metabolismo
7.
Cancer Sci ; 115(4): 1085-1101, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38287908

RESUMO

Regulator of G protein signaling 1 (RGS1) is closely associated with the tumor immune microenvironment and is highly expressed in various tumors and immune cells. The specific effects of RGS1 in the dynamic progression from chronic gastritis to gastric cancer have not been reported, and the role of tumor-associated macrophages (TAMs) is also unclear. In the present study, RGS1 was identified as an upregulated gene in different pathological stages ranging from chronic gastritis to gastric cancer by using Gene Expression Omnibus (GEO) screening together with pancancer analysis of The Cancer Genome Atlas and clinical prognostic analysis. The results indicated that RGS1 is highly expressed in gastric cancer and has potential prognostic value. We confirmed through in vivo experiments that RGS1 inhibited the proliferation of gastric cancer cells and promoted apoptosis, which was further corroborated by in vitro experiments. Additionally, RGS1 influenced cell migration and invasion. In our subsequent investigation of RGS1, we discovered its role in the immune response. Through analyses of single-cell and GEO database data, we confirmed its involvement in immune cell regulation, specifically TAM activation. Subsequently, we conducted in vivo and in vitro experiments to confirm the involvement of RGS1 in polarizing M1 macrophages while indirectly regulating M2 macrophages through tumor cells. In conclusion, RGS1 could be a potential target for the transformation of chronic gastritis into gastric cancer and has a measurable impact on TAMs, which warrants further in-depth research.


Assuntos
Gastrite , Neoplasias Gástricas , Humanos , Macrófagos Associados a Tumor/metabolismo , Neoplasias Gástricas/patologia , Transdução de Sinais , Proteínas de Ligação ao GTP/metabolismo , Microambiente Tumoral
9.
Cell Prolif ; 57(2): e13534, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37592709

RESUMO

A minority of mouse embryonic stem cells (ESCs) display totipotent features resembling 2-cell stage embryos and are known as 2-cell-like (2C-like) cells. However, how ESCs transit into this 2C-like state remains largely unknown. Here, we report that the overexpression of negative elongation factor A (Nelfa), a maternally provided factor, enhances the conversion of ESCs into 2C-like cells in chemically defined conditions, while the deletion of endogenous Nelfa does not block this transition. We also demonstrate that Nelfa overexpression significantly enhances somatic cell reprogramming efficiency. Interestingly, we found that the co-overexpression of Nelfa and Bcl2 robustly activates the 2C-like state in ESCs and endows the cells with dual cell fate potential. We further demonstrate that Bcl2 overexpression upregulates endogenous Nelfa expression and can induce the 2C-like state in ESCs even in the absence of Nelfa. Our findings highlight the importance of BCL2 in the regulation of the 2C-like state and provide insights into the mechanism underlying the roles of Nelfa and Bcl2 in the establishment and regulation of the totipotent state in mouse ESCs.


Assuntos
Células-Tronco Embrionárias , Células-Tronco Embrionárias Murinas , Animais , Camundongos , Células-Tronco Embrionárias Murinas/metabolismo , Diferenciação Celular , Células-Tronco Embrionárias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
10.
Chin Med J (Engl) ; 137(4): 408-420, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37545027

RESUMO

ABSTRACT: As pancreatic cancer (PC) is highly malignant, its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies. First-line chemotherapies for PC, according to current guidelines, include fluoropyrimidine- and gemcitabine-based regimens. Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC, especially those involving glycolysis and glutamine metabolism, are highly associated with chemoresistance. Additionally, lipid metabolism is a major factor in chemoresistance. However, emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance. This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Gencitabina , Desoxicitidina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Reprogramação Metabólica , Carcinoma Ductal Pancreático/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Linhagem Celular Tumoral
11.
Adv Mater ; : e2310134, 2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38042993

RESUMO

Fluid flow behavior is visualized through particle image velocimetry (PIV) for understanding and studying experimental fluid dynamics. However, traditional PIV methods require multiple cameras and conventional lens systems for image acquisition to resolve multi-dimensional velocity fields. In turn, it introduces complexity to the entire system. Meta-lenses are advanced flat optical devices composed of artificial nanoantenna arrays. It can manipulate the wavefront of light with the advantages of ultrathin, compact, and no spherical aberration. Meta-lenses offer novel functionalities and promise to replace traditional optical imaging systems. Here, a binocular meta-lens PIV technique is proposed, where a pair of GaN meta-lenses are fabricated on one substrate and integrated with a imaging sensor to form a compact binocular PIV system. The meta-lens weigh only 116 mg, much lighter than commercial lenses. The 3D velocity field can be obtained by the binocular disparity and particle image displacement information of fluid flow. The measurement error of vortex-ring diameter is ≈1.25% experimentally validates via a Reynolds-number (Re) 2000 vortex-ring. This work demonstrates a new development trend for the PIV technique for rejuvenating traditional flow diagnostic tools toward a more compact, easy-to-deploy technique. It enables further miniaturization and low-power systems for portable, field-use, and space-constrained PIV applications.

12.
Transl Anim Sci ; 7(1): txad122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38084294

RESUMO

The objective of this study was to investigate the effects of concomitantly increasing supplementation of Ca and phytase on growth performance, balance of Ca and P, and bone mineralization in nursery pigs. There were eight experimental diets. The positive control (PC) one and two were formulated to contain 0.64% and 0.85% total Ca, respectively, whereas the dietary concentrations of other nutrients were identical and adequate. The negative control (NC) was deficient in total Ca (0.48%) and total P (0.41%). Five combinations of incremental levels of Ca and phytase (0.48% and 1,750 phytase units [FYT]/kg, 0.52% and 2,000 FYT/kg, 0.55% and 2,250 FYT/kg, 0.59% and 2,600 FYT/kg, and 0.63% and 3,000 FYT/kg) were added to the NC to establish the remaining five experimental diets. Each diet was fed to six pens of six pigs (three barrows and three gilts per pen). All diets contained 3 g/kg TiO2, and fecal samples were collected from each pen during the trial. In the end, one pig per pen was euthanized to collect the right tibia and urine in bladder. The results showed that the pigs of NC gained less weight, consumed less feed, and utilized feed less efficiently than their counterparts fed the PC and the treatments with phytase (P < 0.01). With increasing supplementation of Ca and phytase, there was a tendency for gain:feed to decrease (P < 0.10). There was a significant reduction in bone dry weight; and in percentages, as well as weights of bone ash, Ca, and P; in pigs of NC compared with pigs of PC1, PC2, or phytase treatments. In comparison to PC2, PC1 and phytase treatments resulted in a higher percentage of bone P and greater weights of bone ash, Ca, and P (P < 0.05). There was no significant effect of concurrent supplementation of Ca and phytase on bone mineralization. The NC had significantly lower apparent total tract digestibility (ATTD) of Ca and P, lower concentrations of digestible Ca and P, but a higher ATTD Ca/ATTD P ratio than PC1, PC2, or the phytase treatments. The averages of ATTD of Ca and P in treatments with phytase were significantly higher than PC1 or PC2 (P < 0.01). With increasing addition of Ca and phytase, the ATTD of P, digestible Ca and P, and the ATTD Ca/ATTD P ratio increased linearly (P < 0.05), which contrasted with a linear reduction in ATTD of Ca (P < 0.05). Meanwhile, there was a linear (P < 0.01) increase in the concentration of urinary Ca. In conclusion, increasing the dietary supplementation of phytase in conjunction with the increasing dietary Ca level increased the dietary ATTD Ca/ATTD P ratio without damaging the absorption of P in the current study. The higher ATTD Ca/ATTD P ratio did not improve the bone mineralization markedly and thus the extra Ca was voided through urine.

13.
World J Gastrointest Surg ; 15(11): 2553-2563, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38111756

RESUMO

BACKGROUND: Although the location of proximal cancer of the remnant stomach is the same as that of primary proximal cancer of the stomach, its clinical characteristics and prognosis are still controversial. AIM: To evaluate the clinicopathological features and prognosis factors of gastric stump cancer (GSC) and primary proximal gastric cancer (PGC). METHODS: From January, 2005 to December, 2016, 178 patients with GSC and 957 cases with PGC who received surgical treatment were enrolled. Patients in both groups underwent 1:1 propensity score matching analysis, and both clinical and pathological data were systematically collected for statistical purposes. Quality of life was evaluated by the C30 and STO22 scale between GSC-malignant (GSC following gastric cancer) and GSC-benign (GSC following benign lesions of the stomach). RESULTS: One hundred and fifty-two pairs were successfully matched after propensity score matching analysis. Of the 15 demographic and pathological variables collected, the analysis further revealed that the number of lymph nodes and positive lymph nodes were different prognostic and clinicopathological factors between PGC and GSC. Univariate and multivariate analyses showed that gender, differentiation degree and tumor-node-metastasis stage were independent risk factors for patients with GSC. Gender, vascular invasion, differentiation degree, depth of infiltration, positive lymph nodes, and tumor-node-metastasis stage were independent risk factors for patients with PGC. The 5-year overall survival and cancer-specific survival of patients with GSC were significantly lower than those in the PGC group, the scores for overall quality of life in the GSC-malignant group were lower than the GSC-benign, and the differences were statistically significant. CONCLUSION: The differences in clinicopathological characteristics between GSC and PGC were clarified, and PGC had a better prognosis than GSC.

14.
Eur J Pharmacol ; 960: 176128, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37866747

RESUMO

Programmed cell death receptor/ligand 1 (PD-1/PD-L1) blockade therapy for various cancers induces itch. However, few studies have evaluated the mechanism underlying PD-1/PD-L1 inhibitor-induced itch. This study aimed to establish and evaluate a mouse model of acute itch induced by PD-1/PD-L1 inhibitors and to explore the role of the PD-1/PD-L1 pathway in chronic itch. The intradermal injection of the PD-1/PD-L1 small molecule inhibitors, or anti-PD-1/PD-L1 antibodies in the nape of the neck in the mice elicited intense spontaneous scratches. The model was evaluated using pharmacological methods. The number of scratches was reduced by naloxone but not by antihistamines or the transient receptor potential (TRP) channel inhibitor. Moreover, the PD-1 receptor was detected in the spinal cord of the mouse models of chronic itch that exhibited acetone, diethyl ether, and water (AEW)-induced dry skin, imiquimod-induced psoriasis, and 1-fluoro-2,4-dinitrobenzene (DNFB)-induced allergic contact dermatitis. Intrathecal PD-L1 (1 µg, 4 times a week for 1 week) suppressed the activation of the microglia in the spinal dorsal horn to relieve the chronic itch that was elicited by imiquimod-induced psoriasis and DNFB-induced allergic contact dermatitis. Although the activation of the microglia in the spinal dorsal horn was not detected in the AEW-treated mice, intrathecal PD-L1 still reduced the number of scratches that were elicited by AEW. Our findings suggest that histamine receptor inhibitors or TRP channel inhibitors have limited effects on PD-1/PD-L1 inhibitor-induced itch and that spinal PD-1 is important for the spinal activation of the microglia, which may underlie chronic itch.


Assuntos
Dermatite Alérgica de Contato , Psoríase , Animais , Camundongos , Receptor de Morte Celular Programada 1 , Dinitrofluorbenzeno/efeitos adversos , Antígeno B7-H1 , Imiquimode/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Prurido/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Dermatite Alérgica de Contato/tratamento farmacológico , Modelos Animais de Doenças , Psoríase/tratamento farmacológico , Camundongos Endogâmicos C57BL
15.
Food Res Int ; 172: 113142, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689906

RESUMO

Umami peptides have received extensive attention due to their ability to enhance flavors and provide nutritional benefits. The increasing demand for novel umami peptides and the vast number of peptides present in food call for more efficient methods to screen umami peptides, and further exploration is necessary. Therefore, the purpose of this study is to develop deep learning (DL) model to realize rapid screening of umami peptides. The Umami-BERT model was devised utilizing a novel two-stage training strategy with Bidirectional Encoder Representations from Transformers (BERT) and the inception network. In the pre-training stage, attention mechanisms were implemented on a large amount of bioactive peptides sequences to acquire high-dimensional generalized features. In the re-training stage, umami peptide prediction was carried out on UMP789 dataset, which is developed through the latest research. The model achieved the performance with an accuracy (ACC) of 93.23% and MCC of 0.78 on the balanced dataset, as well as an ACC of 95.00% and MCC of 0.85 on the unbalanced dataset. The results demonstrated that Umami-BERT could predict umami peptides directly from their amino acid sequences and exceeded the performance of other models. Furthermore, Umami-BERT enabled the analysis of attention pattern learned by Umami-BERT model. The amino acids Alanine (A), Cysteine (C), Aspartate (D), and Glutamicacid (E) were found to be the most significant contributors to umami peptides. Additionally, the patterns of summarized umami peptides involving A, C, D, and E were analyzed based on the learned attention weights. Consequently, Umami-BERT exhibited great potential in the large-scale screening of candidate peptides and offers novel insight for the further exploration of umami peptides.


Assuntos
Alanina , Peptídeos , Sequência de Aminoácidos , Aminoácidos , Cisteína
16.
FASEB J ; 37(9): e23111, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37531300

RESUMO

The post-transfer developmental capacity of bovine somatic cell nuclear transfer (SCNT) blastocysts is reduced, implying that abnormalities in gene expression regulation are present at blastocyst stage. Chromatin accessibility, as an indicator for transcriptional regulatory elements mediating gene transcription activity, has heretofore been largely unexplored in SCNT embryos, especially at blastocyst stage. In the present study, single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) of in vivo and SCNT blastocysts were conducted to segregate lineages and demonstrate the aberrant chromatin accessibility of transcription factors (TFs) related to inner cell mass (ICM) development in SCNT blastocysts. Pseudotime analysis of lineage segregation further reflected dysregulated chromatin accessibility dynamics of TFs in the ICM of SCNT blastocysts compared to their in vivo counterparts. ATAC- and ChIP-seq results of SCNT donor cells revealed that the aberrant chromatin accessibility in the ICM of SCNT blastocysts was due to the persistence of chromatin accessibility memory at corresponding loci in the donor cells, with strong enrichment of trimethylation of histone H3 at lysine 4 (H3K4me3) at these loci. Correction of the aberrant chromatin accessibility through demethylation of H3K4me3 by KDM5B diminished the expression of related genes (e.g., BCL11B) and significantly improved the ICM proliferation in SCNT blastocysts. This effect was confirmed by knocking down BCL11B in SCNT embryos to down-regulate p21 and alleviate the inhibition of ICM proliferation. These findings expand our understanding of the chromatin accessibility abnormalities in SCNT blastocysts and BCL11B may be a potential target to improve SCNT efficiency.


Assuntos
Cromatina , Técnicas de Transferência Nuclear , Animais , Bovinos , Cromatina/genética , Cromatina/metabolismo , Blastocisto/metabolismo , Desenvolvimento Embrionário/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo
17.
Reproduction ; 166(4): 285-297, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37490350

RESUMO

In brief: Early embryonic development in goats is a complex and an important process. This study identified a novel long non-coding RNA (lncRNA), lncRNA3720, that appears to affect early embryonic development in goats through histone variants. Abstract: Although abundant lncRNAs have been found to be highly expressed in early embryos, the functions and mechanisms of most lncRNAs in regulating embryonic development remain unclear. This study was conducted to identify the key lncRNAs during embryonic genome activation (EGA) for promoting embryonic development after somatic cell nuclear transfer (SCNT) in goats. We screened and characterized lncRNAs from transcriptome data of in vitro-fertilized, two-cell (IVF-2c) and eight-cell embryos (IVF-8c) and eight-cell SCNT embryos (SCNT-8c). We obtained 12 differentially expressed lncRNAs that were highly expressed in IVF-8c embryos compared to IVF-2c and less expressed in SCNT-8c embryos. After target gene prediction, expression verification, and functional deletion experiments, we found that the expression level of lncRNA3720 affected the early embryonic development in goats. We cloned full-length lncRNA3720 and over-expressed it in goat fetal fibroblasts (GFFs). We identified histone variants by analyzing the transcriptome data from both GFFs and embryos. Gene annotation of the gene library and the literature search revealed that histone variants may have important roles in early embryo development, so we selected them as the potential target genes for lncRNA3720. Lastly, we compensated for the low expression of lncRNA3720 in SCNT embryos by microinjection and showed that the development rate and quality of SCNT embryos were significantly improved. We speculate that lncRNA3720 is a key promoter of embryonic development in goats by interacting with histone variants.


Assuntos
RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Histonas/metabolismo , Cabras/genética , Embrião de Mamíferos , Técnicas de Transferência Nuclear/veterinária , Desenvolvimento Embrionário/genética , Fertilização in vitro , Clonagem de Organismos
18.
Biol Reprod ; 109(3): 282-298, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37498179

RESUMO

In vitro maturation of mammalian oocytes is an important means in assisted reproductive technology. Most bovine immature oocytes complete nuclear maturation, but less than half develop to the blastocyst stage after fertilization. Thus, inefficient in vitro production is mainly caused by a suboptimal in vitro culture process, in which oocyte quality appears to be the limiting factor. In our study, a potential maternal regulator, C-X-C motif chemokine ligand 12, was identified by analyzing transcriptome data. C-X-C motif chemokine ligand 12 supplementation promoted the developmental potential of oocytes by improving protein synthesis and reorganizing cortical granules and mitochondria during in vitro maturation, which eventually increased blastocyst formation efficiency and cell number after parthenogenesis, fertilization, and cloning. All these promoting effects by C-X-C motif chemokine ligand 12 were achieved by activating SH2 domain-containing tyrosine phosphatase 2, thereby promoting the mitogen-activated protein kinase signaling pathway. These findings provide an in vitro maturation system that closely resembles the maternal environment to provide high-quality oocytes for in vitro production.


Assuntos
Oócitos , Domínios de Homologia de src , Bovinos , Animais , Ligantes , Oócitos/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Quimiocinas/metabolismo , Tirosina/metabolismo , Técnicas de Maturação in Vitro de Oócitos/veterinária , Blastocisto/metabolismo , Fertilização in vitro , Mamíferos/metabolismo
19.
Gene ; 881: 147620, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37433356

RESUMO

Nuclear factor 1 X-type (Nfix) is a transcription factor related to mental and physical development. However, very few studies have reported the effects of Nfix on cartilage. This study aims to reveal the influence of Nfix on the proliferation and differentiation of chondrocytes, and to explore its potential action mechanism. We isolated primary chondrocytes from the costal cartilage of newborn C57BL/6 mice and with Nfix overexpression or silencing treatment. We used Alcian blue staining and found that Nfix overexpression significantly promoted ECM synthesis in chondrocytes while silencing inhibited ECM synthesis. Using RNA-seq technology to study the expression pattern of Nfix in primary chondrocytes. We found that Nfix overexpression significantly up-regulated genes that are related to chondrocyte proliferation and extracellular matrix (ECM) synthesis and significantly down-regulated genes related to chondrocyte differentiation and ECM degradation. Nfix silencing, however, significantly up-regulated genes associated with cartilage catabolism and significantly down-regulated genes associated with cartilage growth promotion. Furthermore, Nfix exerted a positive regulatory effect on Sox9, and we propose that Nfix may promote chondrocyte proliferation and inhibit differentiation by stimulating Sox9 and its downstream genes. Our findings suggest that Nfix may be a potential target for the regulation of chondrocyte proliferation and differentiation.


Assuntos
Condrócitos , Fatores de Transcrição NFI , Animais , Camundongos , Cartilagem/metabolismo , Diferenciação Celular/genética , Proliferação de Células/genética , Condrócitos/metabolismo , Camundongos Endogâmicos C57BL , Fatores de Transcrição NFI/genética , Fatores de Transcrição NFI/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo
20.
Sci Prog ; 106(2): 368504231175328, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37201921

RESUMO

The outbreak of major public health emergencies such as the coronavirus epidemic has put forward new requirements for urban emergency management procedures. Accuracy and effective distribution model of emergency support materials, as an effective tool to inhibit the deterioration of the public health sector, have gradually become a research hotspot. The distribution of urban emergency support devices, under the secondary supply chain structure of "material transfer center-demand point," which may involve confusing demands, is studied to determine the actual situation of fuzzy requests under the impact of an epidemic outbreak. An optimization model of urban emergency support material distribution, based on Credibility theory, is first constructed. Then an improved sparrow search algorithm, ISSA, was designed by introducing Sobol sequence, Cauchy variation and bird swarm algorithm into the structure of the classical SSA. In addition, numerical validation and standard test set validation were carried out and the experimental results showed that the introduced improved strategy effectively improved the global search capability of the algorithm. Furthermore, simulation experiments are conducted, based on Shanghai, and the comparison with existing cutting-edge algorithms shows that the designed algorithm has stronger superiority and robustness. And the simulation results show that the designed algorithm can reduce vehicle cost by 4.83%, time cost by 13.80%, etc. compared to other algorithms. Finally, the impact of preference value on the distribution of emergency support materials is analyzed to help decision-makers to develop reasonable and effective distribution strategies according to the impact of major public health emergencies. The results of the study provide a practical reference for the solution of urban emergency support materials distribution problems.


Assuntos
Emergências , Saúde Pública , Humanos , China/epidemiologia , Algoritmos , Simulação por Computador
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