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Prostate cancer (PCa) is a widespread global health concern characterized by elevated rates of occurrence, and there is a need for novel therapeutic targets to enhance patient outcomes. FOXS1 is closely linked to different cancers, but its function in PCa is still unknown. The expression of FOXS1, its prognostic role, clinical significance in PCa, and the potential mechanism by which FOXS1 affects PCa progression were investigated through bioinformatics analysis utilizing public data. The levels of FOXS1 and HILPDA were evaluated in clinical PCa samples using various methods, such as western blotting, immunohistochemistry, and qRT-PCR. To examine the function and molecular mechanisms of FOXS1 in PCa, a combination of experimental techniques including CCK-8 assay, flow cytometry, wound-healing assay, Transwell assay, and Co-IP assay were employed. The FOXS1 expression levels were significantly raised in PCa, correlating strongly with tumor aggressiveness and an unfavorable prognosis. Regulating FOXS1 expression, whether upregulating or downregulating it, correspondingly enhanced or inhibited the growth, migration, and invasion capabilities of PCa cells. Mechanistically, we detected a direct interaction between FOXS1 and HILPDA, resulting in the pathway activation of FAK/PI3K/AKT and facilitation EMT in PCa cells. FOXS1 collaborates with HILPDA to initiate EMT, thereby facilitating the PCa progression through the FAK/PI3K/AKT pathway activation.
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Transición Epitelial-Mesenquimal , Factores de Transcripción Forkhead , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas , Neoplasias de la Próstata , Proteínas Proto-Oncogénicas c-akt , Humanos , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Masculino , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular Tumoral , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/genética , Transducción de Señal , Regulación hacia Arriba , Movimiento Celular , Proliferación Celular , Animales , Ratones , Oncogenes , Pronóstico , Ratones DesnudosRESUMEN
Current studies on cultured meat mainly focus on the muscle tissue reconstruction in vitro, but lack the formation of intramuscular fat, which is a crucial factor in determining taste, texture, and nutritional contents. Therefore, incorporating fat into cultured meat is of superior value. In this study, we employed the myogenic/lipogenic transdifferentiation of chicken fibroblasts in 3D to produce muscle mass and deposit fat into the same cells without the co-culture or mixture of different cells or fat substances. The immortalized chicken embryonic fibroblasts were implanted into the hydrogel scaffold, and the cell proliferation and myogenic transdifferentiation were conducted in 3D to produce the whole-cut meat mimics. Compared to 2D, cells grown in 3D matrix showed elevated myogenesis and collagen production. We further induced fat deposition in the transdifferentiated muscle cells and the triglyceride content could be manipulated to match and exceed the levels of chicken meat. The gene expression analysis indicated that both lineage-specific and multifunctional signalings could contribute to the generation of muscle/fat matrix. Overall, we were able to precisely modulate muscle, fat, and extracellular matrix contents according to balanced or specialized meat preferences. These findings provide new avenues for customized cultured meat production with desired intramuscular fat contents that can be tailored to meet the diverse demands of consumers.
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Transdiferenciación Celular , Pollos , Fibroblastos , Carne , Animales , Fibroblastos/metabolismo , Fibroblastos/citología , Tejido Adiposo/citología , Células Musculares/citología , Desarrollo de Músculos , Proliferación Celular , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Carne in VitroRESUMEN
The quality of pork is significantly impacted by intramuscular fat (IMF). However, the regulatory mechanism of IMF depositions remains unclear. We performed whole-transcriptome sequencing of the longissimus dorsi muscle (IMF) from the high (5.1 ± 0.08) and low (2.9 ± 0.51) IMF groups (%) to elucidate potential mechanisms. In summary, 285 differentially expressed genes (DEGs), 14 differentially expressed miRNAs (DEMIs), 83 differentially expressed lncRNAs (DELs), and 79 differentially expressed circRNAs (DECs) were identified. DEGs were widely associated with IMF deposition and liposome differentiation. Furthermore, competing endogenous RNA (ceRNA) regulatory networks were constructed through co-differential expression analyses, which included circRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 47 DECs) and lncRNA-miRNA-mRNA (containing 6 DEMIs, 6 DEGs, 36 DELs) regulatory networks. The circRNAs sus-TRPM7_0005, sus-MTUS1_0004, the lncRNAs SMSTRG.4269.1, and MSTRG.7983.2 regulate the expression of six lipid metabolism-related target genes, including PLCB1, BAD, and GADD45G, through the binding sites of 2-4068, miR-7134-3p, and miR-190a. For instance, MSTRG.4269.1 regulates its targets PLCB1 and BAD via miRNA 2_4068. Meanwhile, sus-TRPM7_0005 controls its target LRP5 through ssc-miR-7134-3P. These findings indicate molecular regulatory networks that could potentially be applied for the marker-assisted selection of IMF to enhance pork quality.
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Redes Reguladoras de Genes , MicroARNs , ARN Largo no Codificante , Transcriptoma , Animales , Porcinos/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Transcriptoma/genética , Músculo Esquelético/metabolismo , Perfilación de la Expresión Génica/métodos , ARN Circular/genética , Metabolismo de los Lípidos/genética , Tejido Adiposo/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
Recent research has identified ADAR1 as a participant in the regulation of lipid accumulation in mice. However, there are no reports on the roles of ADAR1 in proliferation, apoptosis and differentiation of porcine preadipocytes. In this study, we investigated the role of ADAR1 in differentiation, proliferation and apoptosis of porcine preadipocytes using CCK-8, EdU staining, cell cycle detection, RT-qPCR, Western blot, a triglyceride assay and Oil Red O staining. The over-expression of ADAR1 significantly promoted proliferation but inhibited the differentiation and apoptosis of porcine preadipocytes. The inhibition of ADAR1 had the opposite effect on the proliferation, differentiation and apoptosis of porcine preadipocytes with over-expressed ADAR1. Then, the regulation mechanisms of ADAR1 on preadipocyte proliferation were identified using RNA-seq, and 197 DEGs in response to ADAR1 knockdown were identified. The MAPK signaling pathway is significantly enriched, indicating its importance in mediating fat accumulation regulated by ADAR1. The study's findings will aid in uncovering the mechanisms that regulate fat accumulation through ADAR1.
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Understanding how genetic variants alter phenotypes is an essential aspect of genetic research. Copy number variations (CNVs), a type of prevalent genetic variation in the genome, have been the subject of extensive study for decades. Numerous CNVs have been identified and linked to specific phenotypes and diseases in horses. However, few studies utilizing whole-genome sequencing to detect CNVs in large horse populations have been conducted. Here, we performed whole-genome sequencing on a large cohort of 97 horses from 16 horse populations using Illumina Hiseq panels to detect common and breed-specific CNV regions (CNVRs) genome-wide. This is the largest number of breeds and individuals utilized in a whole genome sequencing-based horse CNV study, employing racing, sport, local, primitive, draft, and pony breeds from around the world. We identified 5,053 to 44,681 breed CNVRs in each of the 16 horse breeds, with median lengths ranging from 1.9 kb to 8 kb. Furthermore, using Vst statistics we analyzed the population differentiation of autosomal CNVRs in three diverse horse populations (Thoroughbred, Yakutian, and Przewalski's horse). Functional annotations were performed on CNVR-overlapping genes and revealed that population-differentiated candidate genes (CTSL, RAB11FIP3, and CTIF) may be involved in selection and adaptation. Our pilot study has provided the horse genetic research community with a large and valuable CNVR dataset and has identified many potential horse breeding targets that require further validation and in-depth investigation.
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Androgen deprivation therapy is a common treatment method for metastatic prostate cancer through lowering androgen levels; however, this therapy frequently leads to the development of castration-resistant prostate cancer (CRPC). This is attributed to the activation of the androgen receptor (AR) signaling pathway. Current treatments targeting AR are often ineffective mostly due to AR gene overexpression and mutations, as well as the presence of splice variants that accelerate CRPC progression. Thus there is a critical need for more specific medication to treat CRPC. Small interfering RNAs have shown great potential as a targeted therapy. This review discusses prostate cancer progression and the role of AR signaling in CRPC, and proposes siRNA-based targeted therapy as a promising strategy for CRPC.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/terapia , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Andrógenos , Antagonistas de Andrógenos/uso terapéutico , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Transducción de SeñalRESUMEN
Pioneer transcription factors (TFs) can directly establish higher-order chromatin interactions to instruct gene transcription. Here, we present a protocol for capturing TF-mediated 3D chromatin interactions using affinity tag-based bridge linker (BL)-Hi-chromatin immunoprecipitation (HiChIP). We describe steps for constructing FLAG-tagged TF, performing BL-HiChIP, and preparing the library. We then detail procedures for sequencing, data analysis, and quality control. This protocol has potential applications in 3D chromatin analysis centered on any specific TF in any type of cells without the need of optimal antibodies. For complete details on the use and execution of this protocol, please refer to Ren et al. (2022).1.
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Cromatina , Factores de Transcripción , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Cromatina/genética , Cromosomas/metabolismo , Regulación de la Expresión Génica , Inmunoprecipitación de Cromatina/métodosRESUMEN
The development of a contamination-free and on-site nucleic acid detection platform with high sensitivity and specificity but low-cost for the detection of pathogenic nucleic acids is critical for infectious disease diagnosis and surveillance. In this study, we combined the recombinase-aided amplification (RAA) with the exonuclease III (Exo III)-assisted signal amplification into a platform for sensitive and specific detection of nucleic acids of African swine fever virus (ASFV). We found that this platform enabled a naked eye visual detection of ASFV at a detection limit as low as 2 copies/µL in 30 min. As expected, no cross-reactivity was observed with other porcine viruses. In addition, to avoid aerosol contamination, a one-tube RAA-Exo III colorimetric assay was also established for the accurate detection of ASFV in clinical samples. Taken together, we developed a rapid, instrument-free, and low-cost Exo III-assisted RAA colorimetric-assay-based nucleic acid detection platform.
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Virus de la Fiebre Porcina Africana , Ácidos Nucleicos , Animales , Porcinos , Sensibilidad y Especificidad , Colorimetría , Ácidos Nucleicos/genética , Recombinasas , Técnicas de Amplificación de Ácido NucleicoRESUMEN
Background: This study aimed to investigate the precise mechanism of zinc-induced apoptosis in human prostate cell lines PC-3 and LNCaP and explore its relationships with the translocation and expression of the orphan receptor TR3 and cytochrome c. Methods: The effects of zinc exposure on apoptosis levels were examined in both PC-3 and LNCaP cells. These cells were treated with exogenous ZnCl2 (100 µM) for 0, 4, 8, 12, and 24 h. Dansylaminoethyl-cyclen (DAEC) fluorescent probe was applied to visualize cellular zinc localization. Zinc-induced apoptosis was identified by Hoechst nuclear staining and flow cytometry analysis. TR3 messenger RNA (mRNA) expression levels were detected by real time-quantitative polymerase chain reaction (PCR). TR3 protein localization and mitochondrial release of cytochrome c were identified by immunofluorescence microscopy. Mitochondrial membrane potential collapse under fluorescence microscopy was examined with a MitoLight probe. Results: Zinc exposure led to gradually increasing apoptosis levels in both LNCaP and PC-3 cells over the 24-h treatment period. The apoptotic effects could be observed as early as after 4 h of zinc treatment in PC-3 cells, with this being seen at 8 h in LNCaP cells. The apoptosis levels of both PC-3 and LNCaP cells began to increase significantly from 8 to 24 h when necrotic cells were also found. TR3 protein translocation from the nucleus to the mitochondria was noted and was accompanied by cytochrome c release into the cytosol from the mitochondria. Interestingly, no significant changes in TR3 mRNA expression levels were observed after zinc treatment. However, the mitochondrial membrane potential of both PC-3 and LNCaP cells gradually disappeared following extended zinc exposure. Conclusions: Zinc-induced apoptosis could be regulated through TR3 protein translocation from the nucleus to the mitochondria in prostate cancer cells without notable changes in TR3 mRNA levels. The direct effect of zinc on the mitochondria was associated with the release of cytochrome c into the cytosol through the mitochondrial targeting of TR3 protein.
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Horticultural crops are greatly disturbed by severe abiotic stress conditions. This is considered one of the major threats to the healthy lives of the human population. Salicylic acid (SA) is famous as one of the multifunctional phytohormones that are widely found in plants. It is also an important bio-stimulator involved in the regulation of growth and the developmental stages of horticultural crops. The productivity of horticultural crops has been improved with the supplemental use of even small amounts of SA. It has good capability to reduce oxidative injuries that occur from the over-production of reactive oxygen species (ROS), potentially elevated photosynthesis, chlorophyll pigments, and stomatal regulation. Physiological and biochemical processes have revealed that SA enhances signaling molecules, enzymatic and non-enzymatic antioxidants, osmolytes, and secondary metabolites activities within the cell compartments of plants. Numerous genomic approaches have also explored that SA regulates transcriptions profiling, transcriptional apprehensions, genomic expression, and metabolism of stress-related genes. Many plant biologists have been working on SA and its functioning in plants; however, its involvement in the enhancement of tolerance against abiotic stress in horticultural crops is still unidentified and needs more attention. Therefore, the current review is focused on a detailed exploration of SA in physiological and biochemical processes in horticultural crops subjected to abiotic stress. The current information is comprehensive and aims to be more supportive of the development of higher-yielding germplasm against abiotic stress.
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Bladder cancer (BC) is one of the most often reported malignancies globally, with a high recurrence rate and associated morbidity and mortality, especially in advanced BC. There has been a surge in the number of molecular targets revealed for BC prognosis and treatment. However, there is still a great need to discover novel biomarkers. Consequently, the current study investigated biomarkers that might indicate the progression of bladder cancer. In this study, bioinformatics analysis was done on a single GEO dataset, and TCGA-BLCA information was connected with differentially expressed genes (DEGs). The levels of mRNA and protein expression were validated using qRT-PCR. According to our findings, CRYAB, ECM1, ALDOB, AOC, GPX3, IGFBP7, AQP2, LASS2, TMEM176A, GALNT1, and LASS2 were highly enriched in cell division, identical protein binding, and developmental process in bladder cancer patients. In addition, among the highly differentiated genes, ECM1, GALNT1, LASS2, and GPX3 showed significant molecular alterations in BC, which are crucial for marker identification. Moreover, the mRNA, CNVs, and protein levels of ECM1, GALNT1, LASS2, and GPX3 were significantly increased in BC patients. Our predictions and analysis studies stated that these four genes act as urine biomarkers and played a crucial role in disease prognosis and the therapeutic process of bladder cancer. Our outcomes showed that these four novel urine biomarkers have the potential to provide innovative diagnostics, early predictions, and disease targets, ultimately improving the BC patient's prognosis.
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Biomarcadores de Tumor , Neoplasias de la Vejiga Urinaria , Humanos , Biomarcadores de Tumor/genética , Acuaporina 2 , Pronóstico , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , ARN Mensajero/genética , Proteínas de la Matriz Extracelular/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
Urolithiasis is a common urological disorder, which causes considerable morbidity in both genders at all age groups worldwide. Though treatment options such as diuretics and non-invasive techniques to disintegrate the deposits are available, but often they are found less effective in the clinics. In this work, we planned to investigate the ameliorative effects of daidzin against the ethylene glycol (EG)-induced urolithiasis in rats. The male albino rats were distributed into four groups (n = 6) as control (group I), urolithiasis induced by the administration of 0.75% EG (group II), urolithiasis induced rats treated with 50 mg/kg of daidzin (group III), and urolithiasis rats treated with standard drug 750 mg/kg of cystone (group IV). The urine volume, pH, and total protein in the urine were assessed. The activities of marker enzymes in both plasma and kidney tissues were analyzed using assay kits. The levels of kidney function markers such as calcium, oxalate, urea, creatinine, uric acid, magnesium, BUN, and phosphorous were estimated using assay kits. The status of antioxidants and inflammatory cytokines were also examined using kits. The renal tissues were examined by histopathological analysis. Our results revealed that the daidzin treatment effectively decreased the urine pH and protein level and increased the urine volume in the urolithiasis rats. Daidzin decreased the calcium, oxalate, uric acid, and urea, creatinine, and BUN levels and also improved the magnesium and phosphorus in the urolithiasis rats. The activities of AST, ALT, ALP, GGT, and LDH were effectively reduced by the daidzin in both serum and renal tissue. Daidzin also reduced the inflammatory marker and increased the antioxidant levels. Histopathology results also proved the therapeutic effects of daidzin. Together, our results displayed that daidzin is effective in the amelioration of EG-induced urolithiasis in rats.
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Riñón , Urolitiasis , Femenino , Masculino , Ratas , Antioxidantes/metabolismo , Calcio/metabolismo , Creatinina , Glicol de Etileno/efectos adversos , Glicol de Etileno/metabolismo , Riñón/metabolismo , Magnesio/metabolismo , Oxalatos/efectos adversos , Oxalatos/metabolismo , Extractos Vegetales/farmacología , Urea , Ácido Úrico/metabolismo , Ácido Úrico/farmacología , Urolitiasis/inducido químicamente , Urolitiasis/tratamiento farmacológico , Urolitiasis/metabolismo , AnimalesRESUMEN
Muscle stem cells (MuSCs) are essential for skeletal muscle development and regeneration, ensuring muscle integrity and normal function. The myogenic proliferation and differentiation of MuSCs are orchestrated by a cascade of transcription factors. In this study, we elucidate the specific role of transcription factor 12 (Tcf12) in muscle development and regeneration based on loss-of-function studies. Muscle-specific deletion of Tcf12 cause muscle weight loss owing to the reduction of myofiber size during development. Inducible deletion of Tcf12 specifically in adult MuSCs delayed muscle regeneration. The examination of MuSCs reveal that Tcf12 deletion resulted in cell-autonomous defects during myogenesis and Tcf12 is necessary for proper myogenic gene expression. Mechanistically, TCF12 and MYOD work together to stabilise chromatin conformation and sustain muscle cell fate commitment-related gene and chromatin architectural factor expressions. Altogether, our findings identify Tcf12 as a crucial regulator of MuSCs chromatin remodelling that regulates muscle cell determination and participates in skeletal muscle development and regeneration.
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Cromatina , Proteína MioD , Proteína MioD/genética , Proteína MioD/metabolismo , Cromatina/genética , Cromatina/metabolismo , Músculo Esquelético/metabolismo , Desarrollo de Músculos/genética , MioblastosRESUMEN
BACKGROUND: Bladder cancer (BLCA) is one of the most common genitourinary malignancies in the world, but its pathogenic genes have not been fully identified and the treatment outcomes are still unsatisfactory. Although the members of 2', 5'-oligoadenylate synthetase (OAS) gene family are known involved in some tumorous biological processes, the roles of the OAS gene family in BLCA are still undetermined. METHODS: By combining vast bioinformatic datasets analyses of BLCA and the experimental verification on clinical BLCA specimen, we identified the expressions and biological functions of OAS gene family members in BLCA with comparison to normal bladder tissues. RESULTS: The expression levels of OAS gene family members were higher in BLCA than in normal bladder tissues. The expression levels of most OAS genes had correlations with genomic mutation and methylation, and with the infiltration levels of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells in the microenvironment of BLCA. In addition, high expressions of OAS1, OAS2, OAS3, and OASL predicted better overall survival in BLCA patients. CONCLUSIONS: The highly expressed OAS genes in BLCA can reflect immune cells infiltration in the tumor microenvironment and predict the better overall survival of BLCA, and thus may be considered as a signature of BLCA. The study provides new insights into the diagnosis, treatment, and prognosis of BLCA.
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2',5'-Oligoadenilato Sintetasa , Neoplasias de la Vejiga Urinaria , 2',5'-Oligoadenilato Sintetasa/genética , Nucleótidos de Adenina , Humanos , Ligasas , Oligorribonucleótidos , Pronóstico , Microambiente Tumoral/genética , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
Spatial chromatin structure is crucial for understanding the early growth and development of porcine skeletal muscle. However, its characteristic of 3D architecture and elaborate regulation of gene transcription remains unclear. In this study, ChIA-PET method is used to study the changes of early chromatin three-dimensional structure in skeletal muscle of lean type Yorkshire pig and fat type Meishan pig. Integrating the in situ Hi-C data revealed the 3D architecture and long-range interaction of the porcine muscle. The results showed the CTCF/RNAPII mediated long-range interaction shapes the different chromatin architecture and dominates the unique regulation of enhancers. In addition, the results revealed that key myogenic genes like ssc-mir-1 had a unique enhancer regulation function in myogenesis. Interestingly, the FGF6 gene is of breed-specific regulation, implying the difference between two breeds in skeletal muscle development. Our research thus may provide a clue for the porcine genetic improvement of skeletal muscle.
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Cromatina , Músculo Esquelético , Porcinos , AnimalesRESUMEN
Expression of key transcription factors can induce transdifferentiation in somatic cells; however, this conversion is usually incomplete due to undefined intrinsic barriers. Here, we employ MyoD-induced transdifferentiation of fibroblasts as a model to illustrate the chromatin structures that impede the cell-fate transition. Focusing on the three-dimensional (3D) chromatin interactions, we show that MyoD directly establishes chromatin loops to activate myogenic transcriptional program. Similarly, dynamic changes of CTCF-mediated chromatin interactions are favorable for fibroblast-to-myoblast conversion. However, a substantial portion of CTCF-mediated chromatin interactions remain stable, and the associated genes are steady in expression and enriched for fibroblast function that may restrict cell-identity transformation. Temporal CTCF depletion can interrupt the resistant chromatin loops to enhance myogenic transdifferentiation in mice, pig, and chicken fibroblasts. Therefore, during induced transdifferentiation, the transcription factor can directly reorganize the 3D chromatin interactions, and perturbation of CTCF-mediated genome topology may resolve the limitations of cell fate transitions.
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Transdiferenciación Celular , Cromatina , Animales , Factor de Unión a CCCTC/metabolismo , Diferenciación Celular/genética , Transdiferenciación Celular/genética , Ratones , Desarrollo de Músculos/genética , PorcinosRESUMEN
Skeletal muscle myogenesis is a sophisticated process controlled by genetic and epigenetic regulators. In animals, one of the key enzymes for the DNA demethylation of 5-methylcytosine is TET2. Although TET2 is essential for muscle development, the mechanisms by which TET2 regulates myogenesis, particularly the implication for muscle stem cells, remains unclear. In the present study, we employed the TET2 knockout mouse model to investigate the function of TET2 in muscle development and regeneration. We observed that TET2 deficiency caused impaired muscle stem cell proliferation and differentiation, resulting in the reduction in both myofiber number and muscle tissue size. Specifically, TET2 maintains calcium homeostasis in muscle stem cells by controlling the DNA methylation levels of the calcium pathway genes. Forced expression of the sodium/calcium exchanger protein SLC8A3 could rescue the myogenic defects in TET2 knockout cells. Our data not only illustrated the vital function of TET2 during myogenesis but also identified novel targets that contribute to calcium homeostasis for enhancing muscle function.
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PURPOSE: Bulbar injury is the most common type of urethral injury. This study investigated the efficacy and safety of a novel technique, local urethral flushing, in preventing stricture formation after blunt bulbar urethra injuries. MATERIALS AND METHODS: This retrospective study included 205 males diagnosed with straddle injury-induced bulbar urethra injury at the Shanxi Bethune Hospital and First Hospital of Shanxi Medical University between January 2015 and January 2019. Patients were diagnosed by retrograde urethrography and classified as partial or complete urethral rupture according to the urethral integrity after injury. Complete urethral rupture patients received suprapubic cystostomy and received urethroplasty 3 months later. Patients with partial urethral rupture underwent endoscopic urethral realignment by cystoscopic guide-wire guided catheterization. Patients with both injury types were divided into 3 groups. The treatment groups received urethral flushing with 0.05% dexamethasone through a secondary ureteral catheter that locked at the urethral lesion. The blank control groups received normal saline. The negative control groups had only a single ureteral catheter placed. Patients were assessed for pain during catheterization, infection, and stenosis, and followed for at least 2 years. RESULTS: Stenosis rates and length were significantly reduced in the normal saline groups, and even further reduced in the dexamethasone groups. The negative control groups had significantly higher infection rates than patients in the dexamethasone or saline groups. CONCLUSIONS: Local urethral flushing with dexamethasone could significantly decrease urethral stenosis rates and severity without increasing patients' discomfort or infection risk.
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Uretra/lesiones , Estrechez Uretral/etiología , Estrechez Uretral/prevención & control , Heridas no Penetrantes/complicaciones , Adulto , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Irrigación Terapéutica/instrumentación , Irrigación Terapéutica/métodos , Resultado del TratamientoRESUMEN
Salamanders are unique among tetrapods in their ability to regenerate their limbs throughout life. Like other poikilothermic amphibians, salamanders also show a remarkable capacity to survive long periods of starvation. Whether the physiological reserves necessary for tissue regeneration are preserved or sacrificed in starved salamanders is unknown. In the current study, we maintained Iberian ribbed newts ( Pleurodeles waltl) under extreme physiological stress to assess the extent of regeneration and identify the molecular and cellular changes that may occur under such conditions. After 19 months of complete food deprivation, the animals exhibited extensive morphological and physiological adaptations but remained behaviorally active and vigilant. Autophagy was elevated in different tissues and the transformed gut microbiota indicated remodeling of the intestinal tract related to autophagy. Upon limb amputation in animals starved for 21 months, regeneration proceeded with progenitor cell proliferation and migration, leading to limb blastema formation. However, limb outgrowth and patterning were substantially attenuated. Blockage of autophagy inhibited cell proliferation and blastema formation in starved animals, but not in fed animals. Hence, tissue autophagy and the regenerative response were tightly coupled only when animals were under stress. Our results demonstrate that under adverse conditions, salamanders can exploit alternative strategies to secure blastema formation for limb regeneration.
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Extremidades/lesiones , Extremidades/fisiología , Regeneración/fisiología , Urodelos/metabolismo , Urodelos/fisiología , Adaptación Fisiológica/fisiología , Animales , Autofagia/fisiología , Privación de Alimentos/fisiología , Microbioma Gastrointestinal/fisiología , HumanosRESUMEN
BACKGROUND: Several studies have confirmed that mobilizing bone marrow-derived stem cells (BMSCs) ameliorates renal function loss following cisplatin-induced acute kidney injury (AKI). The aim of this study was to explore whether the combination of granulocyte-colony stimulating factor (G-CSF) and plerixafor (AMD3100) exerts beneficial effects on renal function recovery in a model of cisplatin-induced nephrotoxicity. METHODS: C57BL/6J mice received intraperitoneal injections of G-CSF (200 µg/kg/day) for 5 consecutive days. On the day of the last injection, the mice received a single subcutaneous dose of AMD3100 (5 mg/kg) 1 h before cisplatin 20 mg/kg injection. Ninety-six hours after cisplatin injection, the mice were euthanized, and blood and tissue samples were collected to assess renal function and tissue damage. Cell mobilization was assessed by flow cytometry (FCM). RESULTS: Mice pretreated with G-CSF/AMD3100 exhibited longer survival and lower serum creatinine and blood urea nitrogen (BUN) levels than mice treated with only G-CSF or saline. Combinatorial G-CSF/AMD3100 treatment attenuated tissue injury and cell death, enhanced cell regeneration, and mobilized a higher number of stem cells in the peripheral blood than G-CSF or saline treatment. Furthermore, the mRNA expression of proinflammatory factors was lower, whereas that of anti-inflammatory factors was higher, in the G-CSF/AMD3100 group than in the G-CSF or saline group (all P < 0.05). CONCLUSIONS: These results suggest that combinatorial G-CSF/AMD3100 therapy mobilizes BMSCs to accelerate improvements in renal functions and prevent cisplatin-induced renal tubular injury. This combinatorial therapy may represent a new therapeutic option for the treatment of AKI and should be further investigated in the future.