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CONTEXT: Aquaporin 7 (AQP7) is selectively expressed in decidualised endometrial stromal cells (ESCs) of mice surrounding the embryonic implantation sites. However, the roles of AQP7 and the underlying mechanism that regulates AQP7 expression in endometrial decidualisation after implantation are still unclear. AIMS: This study aimed to investigate the role of the PI3K-Akt pathway in regulating the expression of AQP7 in ESCs and decidualisation. METHODS: Primary ESCs of pregnant mice were isolated to establish in vitro decidualisation models. PI3K inhibitor LY294002 was added to the decidualisation models, then AQP7 expression, changes in decidualised ESC morphology and expression of decidualisation marker molecules were examined. KEY RESULTS: AQP7 knockdown reduced the proliferation and differentiation of ESCs with in vitro induced decidualisation. Furthermore, when the activity of PI3K was inhibited by LY294002, the expression of AQP7 in decidualised ESCs was decreased and both the proliferation and differentiation of ESCs were significantly reduced. CONCLUSIONS: This indicates that AQP7 is a key molecule involved in endometrial decidualisation and the expression of AQP7 is upregulated through activation of the PI3K-Akt pathways, which promotes the proliferation and differentiation of the ESCs, thus affecting occurrence of decidualisation. IMPLICATIONS: This study may provide a new biomarker for the diagnosis of infertility and a new drug target for the prevention and treatment of infertility.
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Acuaporinas , Infertilidad , Embarazo , Femenino , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Endometrio/metabolismo , Células del Estroma/metabolismo , Acuaporinas/genética , Acuaporinas/metabolismoRESUMEN
Purpose: Inflammation and apoptosis after spinal cord contusion (SCC) are important causes of irreversible spinal cord injury. Interleukin-1ß (IL-1ß) is a key inflammatory factor that promotes the aggravation of spinal cord contusion. However, the specific role and regulatory mechanism of IL-1ß in spinal cord contusion is still unclear. Therefore, this study applied bioinformatics to analyze and mine potential gene targets interlinked with IL-1ß, animal experiments and lentiviral interference technology were used to explore whether IL-1ß affected the recovery of motor function in spinal cord contusion by interfering with PI3K/AKT1 signaling pathway. Method: This study used bioinformatics to screen and analyze gene targets related to IL-1ß. The rat SCC animal model was established by the Allen method, and the Basso Beattie Bresnahan (BBB) score was used to evaluate the motor function of the spinal cord-injured rats. Immunohistochemistry and immunofluorescence were used to localize the expression of IL-1ß and AKT1 proteins in spinal cord tissue. Quantitative polymerase chain reaction and Western blot were used to detect the gene and protein expressions of IL-1ß, PI3K, and AKT1. RNAi technology was used to construct lentivirus to inhibit the expression of IL-1ß, lentiviral interference with IL-1ß was used to investigate the effect of IL-1ß and AKT1 on the function of spinal cord contusion and the relationship among IL-1ß, AKT1, and downstream signaling pathways. Results: Bioinformatics analysis suggested a close relationship between IL-1ß and AKT1. Animal experiments have confirmed that IL-1ß is closely related to the functional recovery of spinal cord contusion. Firstly, from the phenomenological level, the BBB score decreased after SCC, IL-1ß and AKT1 were located in the cytoplasm of neurons in the anterior horn of the spinal cord, and the expression levels of IL-1ß gene and protein in the experimental group were higher than those in the sham operation group. At the same time, the expression of AKT1 gene decreased, the results suggested that the increase of IL-1ß affected the functional recovery of spinal cord contusion. Secondly, from the functional level, after inhibiting the expression of IL-1ß with a lentivirus-mediated method, the BBB score was significantly increased, and the motor function of the spinal cord was improved. Thirdly, from the mechanistic level, bioinformatics analysis revealed the relationship between IL-1ß and AKT1. In addition, the experiment further verified that in the PI3K/AKT1 signaling pathway, inhibition of IL-1ß expression upregulated AKT1 gene expression, but PI3K expression was unchanged. Conclusion: Inhibition of IL-1ß promotes recovery of motor function after spinal cord injury in rats through upregulation of AKT1 expression in the PI3K/AKT1 signaling pathway. Bioinformatics analysis suggested that IL-1ß may affect apoptosis and regeneration by inhibiting the expression of AKT1 in the PI3K/AKT1 signaling pathway to regulate the downstream FOXO, mTOR, and GSK3 signaling pathways; thereby hindering the recovery of motor function in rats after spinal cord contusion. It provided a new perspective for clinical treatment of spinal cord contusion in the future.
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Haploid round spermatids undergo differentiation and morphogenesis during spermiogenesis, resulting in mature spermatozoa. The molecular details underlying this transformation, however, remain poorly understood. In this study, we generated and analyzed germ cell-specific Spata19 knockout mice (Spata19(flox/flox) ; Stra8-Cre; hereafter termed "Spata19 cKO") to assess the model that SPATA19 contributes to mitochondrial function in differentiating spermatids. Spata19-cKO males were infertile, as their sperm exhibited disorganized mitochondrial structure; furthermore, their sperm-abundance of mitochondrial proteins, activities of mitochondrial respiratory chain complex IV, and ATP levels were significantly reduced. Yet, the infertility of Spata19-cKO males was rescued by intracytoplasmic sperm injection, so the sperm are capable of initiating development. Collectively, our findings suggest that SPATA19 plays an important role in sperm motility by regulating the organization and function of the mitochondria.
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Diferenciación Celular/fisiología , Fertilidad/fisiología , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas de Plasma Seminal/metabolismo , Espermátides/metabolismo , Animales , Masculino , Ratones , Ratones Noqueados , Mitocondrias/genética , Proteínas Mitocondriales/genética , Proteínas de Plasma Seminal/genética , Motilidad Espermática/fisiología , Espermátides/citologíaRESUMEN
In this study, to minimize the quality deterioration caused by the retrogradation of starch-based food, the effect and mechanism of oat ß-glucan (OG) on the retrogradation of rice starch was investigated. OG effectively decreased storage modulus (G'), syneresis, and retrogradation enthalpy, indicating the inhibition of short-term and long-term retrogradation of rice starch. The competition for water molecules between the OG and rice starch resulted in partial swelling of the starch granules, consequently reducing particle size, lowering amylose leaching, and decreasing the proportion of short-amylose chains. The microstructure characterization showed that the OG-treated rice starch group (ST-OG) exhibited a smoother and denser surface. Particularly, no notable alterations were observed in the structure of the ST-OG sample during storage, owing to the improved water-holding capacity of starch gel and reduced proportion of free water caused by OG. Furthermore, the ordered structure results confirmed the occurrence of hydrogen bonding between OG and rice starch, which hindered the rearrangement of starch molecules. Therefore, OG is an effective natural additive for controlling the retrogradation of starch-based foods.
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Amilosa , Oryza , beta-Glucanos , Amilosa/química , Oryza/química , Almidón/química , AguaRESUMEN
Purple sweet potato color (PSPC) is a natural anthocyanin pigment that is derived from purple sweet potato storage roots. PSPC possesses a variety of biological activities, including antioxidant, antiinflammatory and neuroprotective effects; however, the detailed effects of PSPC on highfat diet (HFD)induced neuroinflammation remain to be determined. The aim of the present study was to investigate whether PSPC has a protective role in HFDassociated neuroinflammation in the mouse brain and to provide novel insight into the mechanisms of the action. C57BL 6J mice were maintained on a normal diet (10 kcal% fat), a HFD (60 kcal% fat), a HFD with PSPC (700 mg/kg/day) or PSPC alone, which was administrated over 20 weeks. Open field and stepthrough tests were used to evaluate the effects of HFD and PSPC on mouse behavior and memory function. Western blotting and ELISA analyses were used to assess the expression of inflammatory cytokines and the activation of mitogenactivated protein kinase and nuclear factorκB (NFκB). The results demonstrated that PSPC treatment was able to significantly improve the HFDinduced impairment of mouse behavior and memory function, and suppressed the increase in body weight, fat content, hyperlipemia and the level of endotoxin. PSPC treatment also markedly decreased the expression of cyclooxygenase2, inducible nitric oxide synthase, tumor necrosis factorα, interleukin (IL)1ß and IL6, and increased the level of IL10 in the HFDtreated mouse brain. In addition, PSPC inhibited the HFDinduced phosphorylation of extracellular signalregulated kinase (ERK), cJun Nterminal kinase (JNK) and p38, and the activation of NFκB. These findings indicated that PSPC treatment may alleviate HFDinduced neuroinflammation in the mouse brain by inhibiting ERK, JNK, p38 and NF-κB activation.
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Encéfalo/metabolismo , Ipomoea batatas/química , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Extractos Vegetales/química , Animales , Antocianinas/farmacología , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Colesterol/sangre , Ciclooxigenasa 2/metabolismo , Dieta Alta en Grasa , Inflamación , Interleucina-10/análisis , Interleucina-10/metabolismo , Interleucina-6/análisis , Interleucina-6/metabolismo , Ipomoea batatas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/metabolismo , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48h after SAH injury in rats. Specifically evaluating whether mitophagy, through voltage dependant anion channels (VDACs) interacting with microtubule-associated protein 1 light chain 3, could orchestrate the induction of apoptotic and necrotic cell death in neurons, a VDAC1siRNA and an activitor Rapamycian (RAPA), were engaged. One hundred and twelve male Sprague-Dawley rats were randomly divided into 4 groups: Sham, SAH, SAH+VDAC1siRNA, and SAH+RAPA. Outcomes measured included mortality rate, brain edema, BBB disruption, and neurobehavioral testing. We also used western blotting techniques to analyze the expressions of key mitophagic/autophagic proteins and pro-apoptotic protein such as ROS, VDAC1, LC-3II and Caspase-3. Rapamycin treatment significantly improved the mortality rate, cerebral edema, and neurobehavioral deficits; apoptotic and necrotic cell death in neurons were reduced by Rapamycin following SAH injury. However, VDAC1siRNA worsened the brain injury following SAH. Immunohistochemical staining and western blot analysis demonstrated a decreased expression of VDAC1, LC3II, and an increase of ROS and Caspase-3 followed by VDAC1siRNA administration. In conclusion, mitophagy induced by VDAC1 following SAH injury may in fact play a significant role in neuroprotection, the mechanism which may be through the attenuation of the apoptosic and necrosic molecular pathways. This translates a preservation of functional integrity and an improvement in mortality.