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The severe quality of life and economic burden imposed by non-healing skin wounds, infection risks, and treatment costs are affecting millions of patients worldwide. To mitigate these challenges, scientists are relentlessly seeking effective treatment measures. In recent years, extracellular vesicles (EVs) have emerged as a promising cell-free therapy strategy, attracting extensive attention from researchers. EVs mediate intercellular communication, possessing excellent biocompatibility and stability. These features make EVs a potential tool for treating a plethora of diseases, including those related to wound repair. However, there is a growing focus on the engineering of EVs to overcome inherent limitations such as low production, relatively fixed content, and targeting capabilities of natural EVs. This engineering could improve both the effectiveness and specificity of EVs in wound repair treatments. In light of this, the present review will introduce the latest progress in the design methods and experimental paradigms of engineered EVs applied in wound repair. Furthermore, it will comprehensively analyze the current clinical research status and prospects of engineered EVs within this field.
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Vesículas Extracelulares , Qualidade de Vida , Humanos , Comunicação Celular , Terapia Baseada em Transplante de Células e Tecidos , CicatrizaçãoRESUMO
The avian embryo develops within a specialized biological container (eggshell) that contains crucial nutritional compartments (albumen, yolk). We analyzed the transcriptome of ovary and three segments of oviduct, including magnum, isthmus and uterus in the chicken during egg formation. RNA-Seq libraries (42 in total) for ovary and three different parts of the oviduct were sequenced for two different phases of egg formation. We obtained 8365 novel transcripts with an mRNA length longer than 200â¯bp; of these, 6832 were long intergenic non-coding RNA transcripts. We identified 547 differentially expressed genes in magnum (actively secreting albumen versus inactive) and 585 in uterus (active eggshell calcification versus quiescent). By combining QTL, transcriptome and proteome data, we obtained high quality gene lists for chicken egg formation. This is the first study to describe the ovary and oviduct transcriptomes by mRNA sequencing, and to elucidate the global repertoire of functional genes involved in egg formation.
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Galinhas/genética , Ovário/metabolismo , Oviductos/metabolismo , Óvulo/fisiologia , Transcriptoma , Animais , Embrião de Galinha , Galinhas/metabolismo , Feminino , Anotação de Sequência Molecular , RNA Mensageiro/química , RNA Mensageiro/metabolismo , RNA-Seq , Útero/metabolismoRESUMO
Breast muscle yield and feed conversion efficiency are the major breeding aims in duck breeding. Understanding the role of specific transcripts in the muscle and small intestine might lead to the elucidation of interrelated biological processes. In this study, we obtained jejunum and breast muscle samples from two strains of Peking ducks that were sorted by feed conversion ratio (FCR) and breast muscle percentage into two-tailed populations. Ten RNA-Seq libraries were developed from the pooled samples and sequenced using the Hiseq2000 platform. We created a reference duck transcript database using de novo assembly methods, which included 16 663 irredundant contigs with an N50 length of 1530 bp. This new duck reference cDNA dataset significantly improved the mapping rate for RNA-Seq data, from 50% to 70%. Mapping and annotation were followed by Gene Ontology analysis, which showed that numerous genes were differentially expressed between the low and high FCR groups. The differentially expressed genes in the jejunum were enriched in biological processes related to immune response and immune response activation, whereas those in the breast muscle were significantly enriched in biological processes related to muscle cell differentiation and organ development. We identified new candidate genes, that is, PCK1, for improving the FCR and breast muscle yield of ducks and obtained much better reference duck transcripts. This study suggested that de novo assembly is essential when applying transcriptome analysis to a species with an incomplete genome.
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Patos/genética , Jejuno/crescimento & desenvolvimento , Músculo Esquelético/crescimento & desenvolvimento , Transcriptoma , Ração Animal , Animais , Animais Domésticos/genética , Animais Domésticos/crescimento & desenvolvimento , Bases de Dados Genéticas , Patos/crescimento & desenvolvimento , Masculino , CarneRESUMO
Background: Epigenetic DNA methylation is an essential mechanism controlling gene expression and cellular function. Existing analyses with conventional assays have generated significant insights into static states of DNA methylation, but were unable to visualize the dynamics of epigenetic regulation. Aim: We utilized a genomic DNA methylation reporter (GMR) system to track changes in DNA methylation during cardiac differentiation. Methods and Results: The promoter region of Cdk1 (Cyclin-dependent kinase 1) or Sox2 (SRY-Box Transcription Factor 2) gene was cloned upstream of the small nuclear ribonucleoprotein polypeptide N (Snrpn) minimal promoter followed by a fluorescent reporter gene. Mouse induced pluripotent stem cells (iPSCs) carrying Sox2 GMR rapidly lost fluorescent reporter signal upon the induction of differentiation. Cdk1 GMR reporter signal was strong in undifferentiated iPSCs, and gradually decreased during directed cardiomyocyte (CM) differentiation. RT-qPCR and pyrosequencing demonstrated that the reduction of Sox2 and Cdk1 was regulated by hypermethylation of their CpG regions during cardiac differentiation. The present study demonstrated the dynamic DNA methylation along the course of cell cycle withdrawal during CM differentiation. Conclusion: The GMR reporter system can be a useful tool to monitor real-time epigenetic DNA modification at single-cell resolution.
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Regulatory T cells (Tregs) suppress immune responses and inflammation. Here, we described the distinct nonimmunological role of Tregs in fracture healing. The recruitment from the circulation pool, peripheral induction, and local expansion rapidly enriched Tregs in the injured bone. The Tregs in the injured bone displayed superiority in direct osteogenesis over Tregs from lymphoid organs. Punctual depletion of Tregs compromised the fracture healing process, which leads to increased bone nonunion. In addition, bone callus Tregs showed unique T-cell receptor repertoires. Amphiregulin was the most overexpressed protein in bone callus Tregs, and it can directly facilitate the proliferation and differentiation of osteogenic precursor cells by activation of phosphatidylinositol 3-kinase/protein kinase B signaling pathways. The results of loss- and gain-function studies further evidenced that amphiregulin can reverse the compromised healing caused by Treg dysfunction. Tregs also enriched in patient bone callus and amphiregulin can promote the osteogenesis of human pre-osteoblastic cells. Our findings indicate the distinct and nonredundant role of Tregs in fracture healing, which will provide a new therapeutic target and strategy in the clinical treatment of fractures.
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Anfirregulina , Consolidação da Fratura , Linfócitos T Reguladores , Linfócitos T Reguladores/imunologia , Consolidação da Fratura/imunologia , Consolidação da Fratura/fisiologia , Animais , Humanos , Anfirregulina/metabolismo , Camundongos , Osteogênese , Calo Ósseo/imunologia , Masculino , Diferenciação Celular , Transdução de Sinais , Camundongos Endogâmicos C57BL , Fraturas Ósseas/imunologiaRESUMO
The treatment of wounds is a worldwide challenge, and wound infection can affect the effectiveness of wound treatment and further increase the disease burden. Copper is an essential trace element that has been shown to have broad-spectrum antibacterial effects and to be involved in the inflammation, proliferation, and remodeling stages of wound healing. Compared to treatments such as bioactive factors and skin grafts, copper has the advantage of being low-cost and easily available, and has received a lot of attention in wound healing. Recently, biomaterials made by incorporating copper into bioactive glasses, polymeric scaffolds and hydrogels have been used to promote wound healing by the release of copper ions. In addition, copper-incorporated biomaterials with catalytic, photothermal, and photosensitive properties can also accelerate wound healing through antibacterial and wound microenvironment regulation. This review summarizes the antibacterial mechanisms of copper- incorporated biomaterials and their roles in wound healing, and discusses the current challenges. A comprehensive understanding of the role of copper in wounds will help to facilitate new preclinical and clinical studies, thus leading to the development of novel therapeutic tools.
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Materiais Biocompatíveis , Cobre , Cobre/farmacologia , Cicatrização , Hidrogéis , Antibacterianos/farmacologiaRESUMO
AIMS: Accumulating data demonstrates that new adult cardiomyocytes (CMs) are generated throughout life from pre-existing CMs, although the absolute magnitude of CM self-renewal is very low. Modifying epigenetic histone modifications or activating the Hippo-Yap pathway have been shown to promote adult CM cycling and proliferation. Whether these interventions work through common pathways or act independently is unknown. For the first time we have determined whether lysine demethylase 4D (KDM4D)-mediated CM-specific H3K9 demethylation and Hippo pathways inhibition have additive or redundant roles in promoting CM cell cycle re-entry. METHODS AND RESULTS: We found that activating Yap1 in cultured neonatal rat ventricular myocytes (NRVM) through overexpressing Hippo pathway inhibitor, miR-199, preferentially increased S-phase CMs, while H3K9me3 demethylase KDM4D preferentially increased G2/M markers in CMs. Together KDM4D and miR-199 further increased total cell number of NRVMs in culture. Inhibition of Hippo signaling via knock-down of Salvador Family WW Domain Containing Protein 1 (Sav1) also led to S-phase reactivation and additional cell cycle re-entry was seen when combined with KDM4D overexpression. Inducible activating KDM4D (iKDM4D) in adult transgenic mice together with shRNA mediated knock-down of Sav1 (iKDM4D+Sav1-sh) resulted in a significant increase in cycling CMs compared to either intervention alone. KDM4D preferentially induced expression of genes regulating late (G2/M) phases of the cell cycle, while miR-199 and si-Sav1 preferentially up-regulated genes involved in G1/S phase. KDM4D upregulated E2F1 and FoxM1 expression, whereas miR-199 and si-Sav1 induced Myc. Using transgenic mice over-expressing KDM4D together with Myc, we demonstrated that KDM4D/Myc significantly increased CM cell cycling but did not affect cardiac function. CONCLUSIONS: KDM4D effects on CM cell cycle activity are additive with the Hippo-Yap1 pathway and appear to preferentially regulate different cell cycle regulators. This may have important implications for strategies that target cardiac regeneration in treating heart disease.
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Histonas , MicroRNAs , Camundongos , Ratos , Animais , Histonas/metabolismo , Miócitos Cardíacos/metabolismo , Via de Sinalização Hippo , Metilação , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Ciclo Celular/genética , Camundongos Transgênicos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismoRESUMO
Chitosan (CS) and its derivatives have been applied extensively in the biomedical field owing to advantageous characteristics including biodegradability, biocompatibility, antibacterial activity and adhesive properties. The low solubility of CS at physiological pH limits its use in systems requiring higher dissolving ability and a suitable drug release rate. Besides, CS can result in fast drug release because of its high swelling degree and rapid water absorption in aqueous media. As a water-soluble derivative of CS, carboxymethyl chitosan (CMC) has certain improved properties, rendering it a more suitable candidate for wound healing, drug delivery and tissue engineering applications. This review will focus on the antibacterial, anticancer and antitumor, antioxidant and antifungal bioactivities of CMC and the most recently described applications of CMC in wound healing, drug delivery, tissue engineering, bioimaging and cosmetics.
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Quitosana , Quitosana/química , Sistemas de Liberação de Medicamentos/métodos , Antibacterianos/farmacologia , Antibacterianos/química , Fenômenos Químicos , AntifúngicosRESUMO
Due to the low incidence of posteromedial tibial plateau fractures and limited clinical data available, the optimal treatment for this type of fracture remains to be established. This type of fracture, also known as Hoffa-like fracture of the tibial plateau, shares a similar mechanism of injury with the Hoffa fracture of the femoral condyle. In the field of orthopedics, finite element analysis is considered a valuable method to guide clinical decision-making. In this study, four methods used for internal fixation of Hoffa-like fractures of the tibial plateau were compared using computer simulation and applying a finite element method (FEM). The methods compared were lateral L-plate fixation alone (Model A); lateral L-plate combined with posterior anti-slip plate (reconstruction plate/T-plate) fixation (Model B); lateral L-plate combined with posterior hollow nail fixation of the fracture block (Model C); and lateral L-plate combined with anterior hollow nail fixation of the fracture (Model D). The maximum displacement of the model and the maximum stress of the internal fixation material were analyzed by applying an axial load of 2,500 N. The results showed that, in the normal bone model, the maximum displacement of the fracture in Model A was 0.60032 mm, with improved stability through the addition of posterior lateral plate fixation in Model B and reduction of the displacement to 0.38882 mm. The maximum displacement in Model C and Model D was comparable, amounting to 0.42345 mm and 0.42273 mm, respectively. Maximum stress was 1235.6 MPa for Model A, 84.724 MPa for Model B, 99.805 MPa for Model C, and 103.19 MPa for Model D. In the internal fixation analysis of the osteoporotic fracture model, we observed patterns similar to the results of the normal bone model. The results indicated that Model B yielded the overall best results in the treatment of Hoffa-like fractures of the tibial plateau. The orthopedic surgeon may wish to implement these insights into the perioperative algorithm, thereby refining and optimizing clinical patient care. In addition, our findings pave the way for future research efforts.
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Musculoskeletal disorders (MSDs), which include a range of pathologies affecting bones, cartilage, muscles, tendons, and ligaments, account for a significant portion of the global burden of disease. While pharmaceutical and surgical interventions represent conventional approaches for treating MSDs, their efficacy is constrained and frequently accompanied by adverse reactions. Considering the rising incidence of MSDs, there is an urgent demand for effective treatment modalities to alter the current landscape. Phototherapy, as a controllable and non-invasive technique, has been shown to directly regulate bone, cartilage, and muscle regeneration by modulating cellular behavior. Moreover, phototherapy presents controlled ablation of tumor cells, bacteria, and aberrantly activated inflammatory cells, demonstrating therapeutic potential in conditions such as bone tumors, bone infection, and arthritis. By constructing light-responsive nanosystems, controlled drug delivery can be achieved to enable precise treatment of MSDs. Notably, various phototherapy nanoplatforms with integrated imaging capabilities have been utilized for early diagnosis, guided therapy, and prognostic assessment of MSDs, further improving the management of these disorders. This review provides a comprehensive overview of the strategies and recent advances in the application of phototherapy for the treatment of MSDs, discusses the challenges and prospects of phototherapy, and aims to promote further research and application of phototherapy techniques.
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Ongoing research has highlighted the significance of the cross-play of macrophages and mesenchymal stem cells (MSCs). Lysine-specific demethylase 6B (KDM6B) has been shown to control osteogenic differentiation of MSCs by depleting trimethylated histone 3 lysine 27 (H3K27me3). However, to date, the role of KDM6B in bone marrow-derived macrophages (BMDMs) remains controversial. Here, a chromatin immunoprecipitation assay (ChIP) proved that KDM6B derived from osteogenic-induced BMSCs could bind to the promoter region of BMDMs' brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1) gene in a coculture system and activate BMAL1. Transcriptome sequencing and experiments in vitro showed that the overexpression of BMAL1 in BMDM could inhibit the TLR2/NF-κB signaling pathway, reduce pyroptosis, and decrease the M1/M2 ratio, thereby promoting osteogenic differentiation of BMSCs. Furthermore, bone and macrophage dual-targeted GSK-J4 (KDM6B inhibitor)-loaded nanodiscs were synthesized via binding SDSSD-apoA-1 peptide analogs (APA) peptide, which indirectly proved the critical role of KDM6B in osteogenesis in vivo. Overall, we demonstrated that KDM6B serves as a positive circulation trigger during osteogenic differentiation by decreasing the ratio of M1/M2 both in vitro and in vivo. Collectively, these results provide insight into basic research in the field of osteoporosis and bone repair.
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Células-Tronco Mesenquimais , Osteogênese , Fatores de Transcrição ARNTL/metabolismo , Lisina , Diferenciação Celular/genética , Macrófagos/metabolismo , Células CultivadasRESUMO
Multiple rib fractures caused by trauma are common injuries and the internal fixation methods of these injuries have been paid more and more attention by surgeons. Absorbable plates and screws are the effective way to treat rib fractures, but there are no reports on which type of screw fixation method is most effective. In this study, finite element analysis was used to study the effects of five different types of screw fixation methods on anterior rib, lateral rib and posterior rib. The finite element model of the ribs was reconstructed from CT images, and the internal pressure (40 kPa) and intercostal force (30 N) on the surfaces of the ribs were simulated accordingly. An intercostal force of 30 N was applied to the upper and lower surfaces of the ribs to simulate the effect of intercostal muscle force. The pressure of 40 kPa was applied to the inner surface of the ribs, and the normal direction was applied to the inner surface of the ribs. The positive direction was considered inspiratory pressure, and the negative direction was considered expiratory pressure. The results indicate the optimal type of screw fixation on the absorbable plate for rib fractures, and provide a basis and reference for clinical application.
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Background: Primary mucinous lung adenocarcinoma, a subtype of lung adenocarcinoma, is extremely rare. Currently, as there are no specific diagnostic features, it is easy to delay the diagnosis or even to misdiagnose when atypical symptoms are present. Case summary: This case details a patient with primary mucinous lung adenocarcinoma and metastasis to the femoral head. The sole symptom was left hip pain and the initial diagnosis was isolated femoral head necrosis. Conclusions: By presenting this rare case report and the experiences learned from it, we hope to assist clinicians to identify bone metastasis cases with non-typical symptoms in order to make the correct diagnosis as soon as possible.
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Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA; QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.
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Pigs exposed to elevated ambient temperatures exhibit reduced daily gain, alterations in muscle and fat deposition, and decreased health. Negative aspects of gastrointestinal (GI) function, integrity, and permeability also occur. High-intensity sweeteners can ameliorate the negative effects of heat stress (HS) by increasing GI glucagon-like peptide-2 production while capsicum oleoresin has been shown to reduce inflammatory response. The effects of an artificial high-intensity sweetener and capsicum oleoresin (CAPS-SUC; TakTik X-Hit, Pancosma, Switzerland) on growth performance of pigs were examined. Forty-eight pigs (12 wk of age, 43.2 ± 4.3 kg) were assigned to six treatments: thermoneutral conditions (21 ± 1.1 °C; 40% to 70% relative humidity) fed ad libitum with (TN+) or without supplement (TN-), heat stress (35 ± 1 °C; 20% to 40% relative humidity) fed ad libitum with (HS+) or without supplement (HS-), and thermoneutral conditions pair-fed to HS intake with (PFTN+) or without supplement (PFTN-). Supplementation (0.1 g/kg feed) began 2 d prior to the 3-d environmental treatment period. Body weights (BWs) and blood samples were collected on days -1 and 3. Rectal temperature (RT) and respiration rate (RR) were measured thrice daily and the feed intake (FI) was recorded daily. Intestinal sections were collected for histology. Pigs in HS conditions exhibited increased RT (~1.2 °C) and RR (~2.7-fold) compared with TN and PFTN groups (P < 0.01). HS+ animals had increased RR when compared with HS- animals (P < 0.02). Heat stress decreased FI compared with TN. HS and PFTN decreased (P < 0.05) average daily gain compared with TN. Supplement did not alter the BW gain. HS and PFTN decreased (P < 0.05) Gain:Feed compared with TN during environmental treatment. Supplementation with CAPS-SUC increased Gain:Feed by 0.12 (P < 0.05). Circulating glucose concentrations tended to decrease in CAPS-SUC vs. non-supplemented HS and PFTN animals (P ≤ 0.1). Circulating insulin concentrations as well as monocyte count increased in HS compared with PFTN (P < 0.04) but did not differ from TN and likely linked to altered FI. CAPS-SUC increased basophil count (P < 0.02), irrespective of environment. Ileal villus height tended to decrease during HS and PFTN compared with TN (P < 0.08), indicating an effect of intake. Overall, CAPS-SUC supplementation increased pig feed efficiency and may improve immune response.
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Capsicum/química , Suplementos Nutricionais , Transtornos de Estresse por Calor/veterinária , Extratos Vegetais/farmacologia , Edulcorantes/farmacologia , Doenças dos Suínos/prevenção & controle , Ração Animal/análise , Animais , Dieta/veterinária , Digestão , Transtornos de Estresse por Calor/prevenção & controle , Resposta ao Choque Térmico , Temperatura Alta , Insulina/sangue , Intestinos , Taxa Respiratória/efeitos dos fármacos , Edulcorantes/administração & dosagem , SuínosRESUMO
Sex steroid hormones are used in the meat industry due to their ability to regulate muscle hypertrophy. However, the mechanisms underlying their action are not fully elucidated. Recent reports demonstrate that steroid hormones increase oxytocin (OXT) expression in skeletal muscle, indicating that OXT may play a role in satellite cell activity. This hypothesis was tested using steroid hormones (17ß-estradiol [E2]; trenbolone acetate [TBA]), tamoxifen (TAM), OXT, and atosiban (A: OXT receptor inhibitor) applied to bovine satellite cells (BSCs) to investigate BSC regulation by OXT. Oxytocin alone increased fusion index (P < 0.05) but not BSC proliferation. Oxytocin reduced (P < 0.05) apoptotic nuclei and stimulated migration rate (P < 0.05). Similarly, E2 and TBA increased (P < 0.05) BSC proliferation rate, fusion index, and migration and decreased (P < 0.05) apoptotic nuclei. 17ß-Estradiol or TBA supplemented with A had lower (P < 0.05) BSC proliferation rate, fusion index, and migration and more (P < 0.05) apoptotic nuclei compared with E2 or TBA alone. Furthermore, OXT expression increased (P < 0.05) in E2 or TBA-treated proliferating BSC. Oxytocin, E2, and TBA increased (P < 0.05) MyoD and MyoG expression in proliferating BSC. During BSC differentiation, OXT expression increased (P < 0.05) with E2 or TBA treatments. MyoG expression increased (P < 0.05) in OXT, E2, and TBA compared with control. However, A, OXT + A, TAM, TAM + OXT, E2 + TAM, E2 + A, and TBA + A decreased (P < 0.05) MyoG expression during BSC differentiation. These results indicate that OXT is involved in steroid hormone-stimulated BSC activity.
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Bovinos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hormônios Esteroides Gonadais/farmacologia , Ocitocina/fisiologia , Células Satélites de Músculo Esquelético/citologia , Animais , Apoptose/efeitos dos fármacos , Estradiol/farmacologia , Expressão Gênica/efeitos dos fármacos , Masculino , Músculo Esquelético/metabolismo , Ocitocina/genética , Receptores de Ocitocina/antagonistas & inibidores , Células Satélites de Músculo Esquelético/metabolismo , Tamoxifeno/farmacologia , Acetato de Trembolona , Vasotocina/análogos & derivados , Vasotocina/farmacologiaRESUMO
While it is recognized that there are low levels of new cardiomyocyte (CM) formation throughout life, the source of these new CM generates much debate. One hypothesis is that these new CMs arise from the proliferation of existing CMs potentially after dedifferentiation although direct evidence for this is lacking. Here we explore the mechanisms responsible for CM renewal in vivo using multi-reporter transgenic mouse models featuring efficient adult CM (ACM) genetic cell fate mapping and real-time cardiomyocyte lineage and dedifferentiation reporting. Our results demonstrate that non-myocytes (e.g., cardiac progenitor cells) contribute negligibly to new ACM formation at baseline or after cardiac injury. In contrast, we found a significant increase in dedifferentiated, cycling CMs in post-infarct hearts. ACM cell cycling was enhanced within the dedifferentiated CM population. Single-nucleus transcriptomic analysis demonstrated that CMs identified with dedifferentiation reporters had significant down-regulation in gene networks for cardiac hypertrophy, contractile, and electrical function, with shifts in metabolic pathways, but up-regulation in signaling pathways and gene sets for active cell cycle, proliferation, and cell survival. The results demonstrate that dedifferentiation may be an important prerequisite for CM proliferation and explain the limited but measurable cardiac myogenesis seen after myocardial infarction (MI).
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The reproductive system of a female bird is responsible for egg production. The genes highly expressed in oviduct are potentially important. From RNA-seq analysis, C2H9orf152 (an orthologous gene of human C9orf152) was identified as highly expressed in chicken uterus. To infer its function, we obtained and characterized its complete cDNA sequence, determined its spatiotemporal expression, and probed its transcription factor(s) through pharmaceutical approach. Data showed that the complete cDNA sequence was 1468bp long with a 789bp of open reading frame. Compared to other tested tissues, this gene was highly expressed in the oviduct and liver tissues, especially uterus. Its expression in uterus was gradually increased during developmental and reproductive periods, which verified its involvement in the growth and maturity of reproductive system. In contrast, its expression was not significant different between active and quiescent uterus, suggesting the role of C2H9orf152 in reproduction is likely due to its long-term effect. Moreover, based on its 5'-flanking sequence, Foxd3 and Hnf4a were predicted as transcription factors of C2H9orf152. Using berberine or retinoic acid (which can regulate the activities of Hnf4a and Foxd3, respectively), we demonstrated suppression of C2H9orf152 by the chemicals in chicken primary hepatocytes. As retinoic acid regulates calcium metabolism, and Hnf4a is a key nuclear factor to liver, these findings suggest that C2H9orf152 is involved in liver function and calcium metabolism of reproductive system. In conclusion, C2H9orf152 may have a long-term effect on chicken reproductive system by regulating calcium metabolism, suggesting this gene has an important implication in the improvement of egg production and eggshell quality.
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Cálcio/metabolismo , Regulação da Expressão Gênica/fisiologia , Reprodução/fisiologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , Galinhas , Clonagem Molecular , DNA Complementar , Casca de Ovo/fisiologia , Feminino , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Oviposição/genética , Oviposição/fisiologia , FilogeniaRESUMO
OBJECTIVE: To study the factors affecting the long-term prognosis of patients with myasthenia gravis (MG) after thymectomy. METHODS: 170 MG patients who had undergone thymectomies were studied retrospectively. Among them, 124 patients received long-term follow-up for more than 40 months postoperatively. The COX regression analysis model was used to analyze the factors that may influence the long-term prognosis. These factors included thymus pathology, patient gender, age, duration of disease at the time of surgery, preoperative Osserman classification and medication. RESULTS: The research showed that thymus pathology was the single independent factor that affected the postoperative long-term prognosis. The long-term survival rates differed significantly with thymus pathological types: hyperplasia > benign thymoma > atrophy > malignant thymoma (P < 0.05). CONCLUSION: The different pathological types of the thymus were the important factor affecting long-term survival in MG patients after thymectomy.
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Miastenia Gravis/cirurgia , Timectomia/efeitos adversos , Adolescente , Adulto , Idoso , Atrofia/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Hiperplasia/etiologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/mortalidade , Complicações Pós-Operatórias , Prognóstico , Análise de Sobrevida , Taxa de Sobrevida , Timoma/etiologia , Timo/patologia , Timo/cirurgia , Fatores de TempoRESUMO
The healing of diabetic skin wounds is a complex process significantly affected by the hyperglycemic environment. In this context, glucose oxidase (GOx), by catalyzing glucose to produce gluconic acid and hydrogen peroxide, not only modulates the hyperglycemic microenvironment but also possesses antibacterial and oxygen-supplying functions, thereby demonstrating immense potential in the treatment of diabetic wounds. Despite the growing interest in GOx-based therapeutic strategies in recent years, a systematic summary and review of these efforts have been lacking. To address this gap, this review article outlines the advancements in the application of GOx and GOx-like nanozymes in the treatment of diabetic wounds, including reaction mechanisms, the selection of carrier materials, and synergistic therapeutic strategies such as multi-enzyme combinations, microneedle structures, and gas therapy. Finally, the article looks forward to the application prospects of GOx in aiding the healing of diabetic wounds and the challenges faced in translating these innovations to clinical practice. We sincerely hope that this review can provide readers with a comprehensive understanding of GOx-based diabetic treatment strategies, facilitate the rigorous construction of more robust multifunctional therapeutic systems, and ultimately benefit patients with diabetic wounds.