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1.
Theriogenology ; 225: 43-54, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38788628

RESUMEN

Extensive research has been conducted on the role of CXCR3 in immune responses and inflammation. However, the role of CXCR3 in the reproductive system, particularly in oocyte development, remains unknown. In this study, we present findings on the involvement of CXCR3 in the meiotic division process of mouse oocytes. We found CXCR3 was expressed consistently throughout the entire maturation process of mouse oocyte. Inhibition of CXCR3 impaired the asymmetric division of oocyte, while the injection of Cxcr3 mRNA was capable of restoring these defects. Further study showed that inhibition of CXCR3 perturbed spindle migration by affecting LIMK/cofilin pathway-mediated actin remodeling. Knockout of CXCR3 led to an upregulation of actin-binding protein and an increased ATP level in GV-stage oocytes, while maintaining normal actin dynamics during the process of meiosis. Additionally, we noticed the expression level of DYNLT1 is markedly elevated in CXCR3-null oocytes. DYNLT1 bound with the Arp2/3 complex, and knockdown of DYNLT1 in CXCR3-null oocytes impaired the organization of cytoplasmic actin, suggesting the regulatory role of DYNLT1 in actin organization, and the compensatory expression of DYNLT1 may contribute to maintain normal actin dynamics in CXCR3-knockout oocytes. In summary, our findings provide insights into the intricate network of actin dynamics associated with CXCR3 during oocyte meiosis.


Asunto(s)
Actinas , Oocitos , Receptores CXCR3 , Animales , Oocitos/metabolismo , Oocitos/fisiología , Ratones , Actinas/metabolismo , Actinas/genética , Receptores CXCR3/metabolismo , Receptores CXCR3/genética , Femenino , Meiosis/fisiología , Ratones Noqueados
2.
Plant Cell Environ ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38736429

RESUMEN

Day length modulates hypocotyl elongation in seedlings to optimize their overall fitness. Variations in cell growth-associated genes are regulated by several transcription factors. However, the specific transcription factors through which the plant clock increases plant fitness are still being elucidated. In this study, we identified the no apical meristem, Arabidopsis thaliana-activating factor (ATAF-1/2), and cup-shaped cotyledon (NAC) family transcription factor ATAF1 as a novel repressor of hypocotyl elongation under a short-day (SD) photoperiod. Variations in day length profoundly affected the transcriptional and protein levels of ATAF1. ATAF1-deficient mutant exhibited increased hypocotyl length and cell growth-promoting gene expression under SD conditions. Moreover, ATAF1 directly targeted and repressed the expression of the cycling Dof factor 1/5 (CDF1/5), two key transcription factors involved in hypocotyl elongation under SD conditions. Additionally, ATAF1 interacted with and negatively modulated the effects of phytochrome-interacting factor (PIF), thus inhibiting PIF-promoted gene expression and hypocotyl elongation. Taken together, our results revealed ATAF1-PIF as a crucial pair modulating the expression of key transcription factors to facilitate plant growth during day/night cycles under fluctuating light conditions.

3.
J Interpers Violence ; : 8862605241253039, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769876

RESUMEN

Bystanders play a role in school bullying; more specifically, the defending behaviors of bystanders play an important role in stopping bullying. This study explores the relationship between defending behaviors and family functioning in the context of school bullying from a family perspective. The role played by individual characteristics (empathy and gender) in this relationship was also focused on. The participants were 994 adolescents (average age = 13.34 ± 0.92 years) from the east of China. They completed the McMaster Family Assessment Device, the Basic Empathy Scale, and the Defending Behaviors subscale of the Participant Role Questionnaire. After controlling for residence and age, we found that family functioning significantly and positively influenced defending behaviors, and cognitive empathy rather than affective empathy mediated the relationship between family functioning and defending behaviors. In addition, family functioning influenced defending behaviors in boys more strongly than in girls. This study may increase the likelihood that bystanders will engage in defending behaviors by informing interventions for school bullying.

4.
Front Cell Infect Microbiol ; 14: 1374238, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774627

RESUMEN

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future.


Asunto(s)
Bacterias , Neoplasias de la Vesícula Biliar , Microbioma Gastrointestinal , Humanos , Neoplasias de la Vesícula Biliar/microbiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Animales , Disbiosis/microbiología , Factores de Virulencia , Hongos/patogenicidad , Hongos/clasificación
5.
Chem Sci ; 15(19): 7178-7186, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38756822

RESUMEN

In order to investigate the effect of macrocyclization and catenation on the regulation of vibration-induced emission (VIE), the typical VIE luminogen 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) was introduced into the skeleton of a macrocycle and corresponding [2]catenane to evaluate their dynamic relaxation processes. As investigated in detail by femtosecond transient absorption (TA) spectra, the resultant VIE systems revealed precisely tunable emissions upon changing the solvent viscosity, highlighting the key effect of the formation of [2]catenane. Notably, the introduction of an additional pillar[5]arene macrocycle featuring unique planar chirality endows the resultant chiral VIE-active [2]catenane with attractive circularly polarized luminescence in different states. This work not only develops a new strategy for the design of new luminescent systems with tunable vibration induced emission, but also provides a promising platform for the construction of smart chiral luminescent materials for practical applications.

6.
Cancer Gene Ther ; 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802550

RESUMEN

Bladder cancer (BC) is one of the most common malignancies in the male urinary system and currently lacks an optimal treatment strategy. To elucidate the pathogenic mechanisms of BC from the perspective of circular RNAs, we conducted this study. Building upon our previous research, a novel circRNA, circPKN2, captured our interest due to its significant downregulation in BC, and its close association with the prognosis of BC patients. Our research findings indicate that circPKN2 can inhibit the proliferation and migration of BC cells in vitro. Furthermore, we discovered that circPKN2 exerts its anti-cancer effects in BC by promoting ferroptosis. Mechanistic studies revealed that circPKN2 recruits STUB1 to facilitate the ubiquitination of SCD1, thereby suppressing the WNT pathway and promoting ferroptosis in BC. Additionally, our research unveiled the regulatory role of the splicing factor QKI in the biogenesis of circPKN2. Animal studies demonstrated that circPKN2 enhances ferroptosis in BC cells in vivo, inhibiting tumor growth and metastasis. The discovery of the anti-cancer factor circPKN2 holds promise for providing new therapeutic targets in the prevention and treatment of BC.

7.
J Cancer Res Clin Oncol ; 150(5): 264, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767747

RESUMEN

BACKGROUND: Bladder cancer (BCa) is among the most prevalent malignant tumors affecting the urinary system. Due to its highly recurrent nature, standard treatments such as surgery often fail to significantly improve patient prognosis. Our research aims to predict prognosis and identify precise therapeutic targets for novel treatment interventions. METHODS: We collected and screened genes related to the TGF-ß signaling pathway and performed unsupervised clustering analysis on TCGA-BLCA samples based on these genes. Our analysis revealed two novel subtypes of bladder cancer with completely different biological characteristics, including immune microenvironment, drug sensitivity, and more. Using machine learning classifiers, we identified SMAD6 as a hub gene contributing to these differences and further investigated the role of SMAD6 in bladder cancer in the single-cell transcriptome data. Additionally, we analyzed the relationship between SMAD6 and immune checkpoint genes. Finally, we performed a series of in vitro assays to verify the function of SMAD6 in bladder cancer cell lines. RESULTS: We have revealed two novel subtypes of bladder cancer, among which C1 exhibits a worse prognosis, lower drug sensitivity, a more complex tumor microenvironment, and a 'colder' immune microenvironment compared to C2. We identified SMAD6 as a key gene responsible for the differences and further explored its impact on the molecular characteristics of bladder cancer. Through in vitro experiments, we found that SMAD6 promoted the prognosis of BCa patients by inhibiting the proliferation and migration of BCa cells. CONCLUSION: Our study reveals two novel subtypes of BCa and identifies SMAD6 as a highly promising therapeutic target.


Asunto(s)
Aprendizaje Automático , Proteína smad6 , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Pronóstico , Proteína smad6/genética , Proteína smad6/metabolismo , Resistencia a Antineoplásicos/genética , Línea Celular Tumoral , Proliferación Celular , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica
8.
Sheng Li Xue Bao ; 76(1): 45-51, 2024 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-38444130

RESUMEN

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.


Asunto(s)
Dieta Alta en Grasa , Factor A de Crecimiento Endotelial Vascular , Animales , Ratones , Angiogénesis , Catepsina K , Dieta Alta en Grasa/efectos adversos , Proteínas Proto-Oncogénicas c-akt/genética , Factor A de Crecimiento Endotelial Vascular/genética
9.
Front Pharmacol ; 15: 1362382, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444942

RESUMEN

Bile acids (BAs) constitute essential components of cholesterol metabolites that are synthesized in the liver, stored in the gallbladder, and excreted into the intestine through the biliary system. They play a crucial role in nutrient absorption, lipid and glucose regulation, and the maintenance of metabolic homeostasis. In additional, BAs have demonstrated the ability to attenuate disease progression such as diabetes, metabolic disorders, heart disease, and respiratory ailments. Intriguingly, recent research has offered exciting evidence to unveil their potential antitumor properties against various cancer cell types including tamoxifen-resistant breast cancer, oral squamous cell carcinoma, cholangiocarcinoma, gastric cancer, colon cancer, hepatocellular carcinoma, prostate cancer, gallbladder cancer, neuroblastoma, and others. Up to date, multiple laboratories have synthesized novel BA derivatives to develop potential drug candidates. These derivatives have exhibited the capacity to induce cell death in individual cancer cell types and display promising anti-tumor activities. This review extensively elucidates the anticancer activity of natural BAs and synthetic derivatives in cancer cells, their associated signaling pathways, and therapeutic strategies. Understanding of BAs and their derivatives activities and action mechanisms will evidently assist anticancer drug discovery and devise novel treatment.

10.
Adv Sci (Weinh) ; 11(24): e2309407, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38491739

RESUMEN

Flexible pressure sensors play a significant role in wearable devices and electronic skin. Iontronic pressure sensors with high sensitivity, wide measurement range, and high resolution can meet requirements. Based on the significant deformation characteristics of alveoli to improve compressibility, and the ability of the arch to disperse vertical pressure into horizontal thrust to increase contact area, a graded hollow ball arch (GHBA) microstructure is proposed, greatly improving sensitivity. The fabrication of GHBA ingeniously employs a double-sided structure. One side uses mold casting to create convex structures, while the other utilizes the evaporation of moisture during the curing process to form concave structures. At the same time, a novel side-by-side package structure is proposed, ensuring pressure on flexible substrate is maximally transferred to the GHBA microstructure. Within the range of 0.2 Pa-300 kPa, the iontronic pressure sensor achieves a maximum sensitivity of 10 420.8 kPa-1, pressure resolution of 0.1% under the pressure of 100 kPa, and rapid response/recovery time of 40/35 ms. In wearable devices, it is capable of monitoring dumbbell curl exercises and wirelessly correcting sitting positions. In electronic skin, it can non-contactly detect the location of the wind source and achieve object classification prediction when combined with the CNN model.

11.
J Transl Med ; 22(1): 299, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519939

RESUMEN

BACKGROUND: The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid ß-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression. METHODS: Distribution of lipids in GBC was described by LC-MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5' and 3' rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex. RESULTS: Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination. CONCLUSIONS: LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.


Asunto(s)
Carnitina/análogos & derivados , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/genética , Hibridación Fluorescente in Situ , ARN , Lípidos , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Proteínas Nucleares/metabolismo , Proteínas de Unión al ARN/genética
12.
Animals (Basel) ; 14(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38396557

RESUMEN

Oocytes are efficient at reprogramming terminally differentiated cells to a totipotent state. Nuclear transfer techniques can exploit this property to produce cloned animals. However, the overall efficiency is low. The use of umbilical cord mesenchymal stem cells (UC-MSCs) as donor nuclei may increase blastocyst rates, but the exact reasons for this remain unexplored. A single-cell transcriptomic approach was used to map the transcriptome profiles of eight-cell embryos that were in vitro-fertilized and handmade-cloned using umbilical cord mesenchymal stem cells and fibroblasts as nuclear donors. Differences were examined at the chromatin level, the level of differentially expressed genes, the level of histone modifications and the level of DNA methylation. This research provides critical information regarding the use of UC-MSCs as a preferred donor nucleus for nuclear transfer techniques. It also offers unique insights into the mechanism of cellular reprogramming.

13.
Aggress Behav ; 50(2): e22140, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38411030

RESUMEN

Children who experience physical and psychological maltreatment within their family are more likely to become victims of abuse outside the family. In Chinese culture, children's victimization may also be a precursor to parenting behaviors. Nevertheless, the reciprocal relationship between child maltreatment and children's bullying victimization remains unclear, particularly in Chinese culture. This study aimed to evaluate the reciprocal association between child maltreatment and children's bullying victimization in China, as well as its gender differences. A total of 891 children aged 8-11 years in China participated in the study at four time points. The potential reciprocal link was examined using a cross-lagged model. The results indicated that physical abuse predicted children's bullying victimization across four time points, while physical neglect predicted children's bullying victimization during the first three time points. The effects of emotional abuse and neglect were negligible. Conversely, children's bullying victimization consistently predicted various types of parental maltreatment over time. Some gender differences in the relationship were found. The findings emphasized a reciprocal relationship between child maltreatment within the family and children's bullying victimization at school. Understanding the cyclical patterns between child maltreatment and bullying victimization may help improve family education approaches and reduce children's bullying victimization.


Asunto(s)
Acoso Escolar , Maltrato a los Niños , Víctimas de Crimen , Humanos , Niño , Maltrato a los Niños/psicología , Víctimas de Crimen/psicología , Abuso Físico/psicología , Acoso Escolar/psicología , Padres , China
14.
Suicide Life Threat Behav ; 54(2): 349-360, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38284480

RESUMEN

OBJECTIVE: Sleep problems are a significant risk factor for identifying and preventing suicidal involvement among adolescents. However, there is limited evidence to assess the underlying mechanisms between them. This study investigated the longitudinal relationship between sleep problems and suicidal behavior and examined whether this relationship was moderated by negative emotions, low self-control, and nonsuicidal self-injury (NSSI). METHODS: From December 2020 onward, we assessed 1214 Chinese secondary school adolescents (60.7% were boys, aged 13-19 years) three times, 6 months apart. RESULTS: In the direct effects model, sleep problems were found to have a positive impact on adolescent suicidal behavior. In the indirect effects model, we observed that sleep problems were associated with an elevated risk of suicidal behavior through several pathways: one-mediator path of negative emotions, low self-control, and NSSI, respectively; two-mediator path of negative emotions via low self-control, negative emotions via NSSI, and low self-control via NSSI, and three-mediator path from negative emotions to NSSI via low self-control. CONCLUSIONS: This longitudinal study provides evidence that sleep problems in adolescents may increase suicidal behavior by exacerbating negative emotions, weakening self-control, and promoting NSSI. The findings suggest sleep problems should be addressed in suicide prevention and intervention efforts for adolescents.


Asunto(s)
Autocontrol , Conducta Autodestructiva , Trastornos del Sueño-Vigilia , Masculino , Humanos , Adolescente , Femenino , Ideación Suicida , Estudios Longitudinales , Conducta Autodestructiva/psicología , Emociones , Trastornos del Sueño-Vigilia/complicaciones
15.
Angew Chem Int Ed Engl ; 63(12): e202319502, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38279667

RESUMEN

Aiming at the construction of novel stimuli-responsive fluorescent system with precisely tunable emissions, the typical 9,14-diphenyl-9,14-dihydrodibenzo[a, c]phenazine (DPAC) luminogen with attractive vibration-induced emission (VIE) behavior has been introduced into [2]rotaxane as a stopper. Taking advantage of their unique dual stimuli-responsiveness towards solvent and anion, the resultant [2]rotaxanes reveal both tunable VIE and switchable circularly polarized luminescence (CPL). Attributed to the formation of mechanical bonds, DPAC-functionalized [2]rotaxanes display interesting VIE behaviors including white-light emission upon the addition of viscous solvent, as evaluated in detail by femtosecond transient absorption (TA) spectra. In addition, ascribed to the regulation of chirality information transmission through anion-induced motions of chiral wheel, the resolved chiral [2]rotaxanes reveal unique switchable CPL upon the addition of anion, leading to significant increase in the dissymmetry factors (glum ) values with excellent reversibility. Interestingly, upon doping the chiral [2]rotaxanes in stretchable polymer, the blend films reveal remarkable emission change from white light to light blue with significant 6.5-fold increase in glum values up to -0.035 under external tensile stresses. This work provides not only a new design strategy for developing molecular systems with fluorescent tunability but also a novel platform for the construction of smart chiral luminescent materials for practical use.

16.
Environ Toxicol ; 39(1): 289-298, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37705237

RESUMEN

We have previously found that a mixture exposure of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) and cadmium (Cd) causes kidney damage; however, the mechanism was not fully understood. The aryl hydrocarbon receptor (AhR) is a ligand-receptor transcription factor that plays an important role in the adaptive response or metabolic detoxification of environmental toxins. Thus, this study aimed to examine the role of AhR in kidney toxicity. BDE-47 (50 µM) or Cd (5 µM) exposure reduced cell viability in renal tubular epithelial cells (HKC), with a larger effect observed in co-treatment. The cell morphology presented pyroptotic changes, including swollen cells, large bubbles, and plasma membrane pore formation. The gene expressions of AhR, heat shock protein 90 (Hsp90), AhR nuclear translocator (ARNT), and cytochrome P450 1B1 (CYP1B1) were increased, while CYP1A1 was decreased. Reactive oxygen species (ROS) were generated, which was reduced by the AhR antagonist CH223191. The apoptosis, necrosis, and intracellular lactated hydrogenase (LDH) release was elevated, and this was attenuated by N-acetylcysteine (NAC). Furthermore, the pyroptosis pathway was activated with increased protein levels of cleaved-caspase-3 and gasdermin E N-terminal (GSDME-NT), while caspase-8, caspase-3, and GSDME were decreased. These effects were alleviated by NAC and CH223191. Our data demonstrate a combined effect of BDE-47 and Cd on nephrotoxicity by activating AhR to induce ROS contributing to GSDME-dependent pyroptosis, and retardation of the AhR pathway could reduce this toxicity.


Asunto(s)
Cadmio , Receptores de Hidrocarburo de Aril , Receptores de Hidrocarburo de Aril/metabolismo , Cadmio/toxicidad , Caspasa 3/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Piroptosis , Éter , Células Epiteliales/metabolismo
17.
Cancer Lett ; 582: 216515, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-38056687

RESUMEN

Bladder cancer (BC) is a common malignancy in males, and currently lacks ideal therapeutic approaches. Exploring emerging therapeutic targets from the perspective of endogenous peptides to improve the prognosis of bladder cancer patients holds promise. In this study, we have identified CTSGDP-13, a novel endogenous peptide, which demonstrates potential anti-cancer effects in BC. Our findings reveal that CTSGDP-13 can promote ferroptosis in BC cells, both in vitro and in vivo, leading to the inhibition of BC progression. Furthermore, we have identified TRIM25 as a downstream regulatory target of CTSGDP-13. The expression of TRIM25 is significantly upregulated in BC, and its inhibition of ferroptosis promotes BC progression. Mechanistic studies have shown that CTSGDP-13 promotes the ubiquitination and subsequent degradation of TRIM25 by disrupting its interaction with the deubiquitinase USP7. Further investigations indicate that CTSGDP-13 promotes ferroptosis in BC by regulating the USP7/TRIM25/KEAP1 axis. The elucidation of the functional mechanisms of natural CTSGDP-13 and TRIM25 holds promise in providing valuable therapeutic targets for BC diagnosis and treatment.


Asunto(s)
Ferroptosis , Neoplasias de la Vejiga Urinaria , Masculino , Humanos , Proteína 1 Asociada A ECH Tipo Kelch , Micropéptidos , Peptidasa Específica de Ubiquitina 7 , Factor 2 Relacionado con NF-E2 , Neoplasias de la Vejiga Urinaria/patología
18.
Gene ; 894: 147974, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-37944649

RESUMEN

OBJECT: In this study, we aimed to elucidate the role of LUCAT1, a recently identified lncRNA, in ferroptosis within the context of bladder cancer (BC). METHODS: Through a comprehensive array of experimental techniques, including transmission electron microscopy (TEM), RNA pull-down assays, and fluorescence in situ hybridization (FISH), we investigated the molecular interactions and functional consequences associated with LUCAT1 in BC cells. RESULTS: Our findings indicate that LUCAT1 acts as a pivotal regulator in BC, fostering cell proliferation, migration, and invasion, while concurrently impeding ferroptosis. Mechanistically, we unveiled a direct binding between LUCAT1 and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), which governs the mRNA stability of signal transducer and activator of transcription 3 (STAT3). Intriguingly, ectopic expression of STAT3 counteracted the suppressive effect of LUCAT1 on ferroptosis induction in BC cells. Notably, in an in vivo setting, LUCAT1 emerged as a crucial modulator of ferroptosis inhibition in BC by regulating STAT3 mRNA stability. CONCLUSION: Collectively, our study identifies LUCAT1 as a novel oncogenic player, repressing ferroptosis in BC. These findings shed light on the intricate interplay between lncRNAs and ferroptosis in cancer, implicating LUCAT1 as a promising therapeutic target for patients afflicted with BC. Further investigations into the underlying mechanisms governing LUCAT1-mediated ferroptosis resistance are warranted, with the potential to uncover novel strategies for combating BC progression and improving patient outcomes.


Asunto(s)
Ferroptosis , MicroARNs , ARN Largo no Codificante , Neoplasias de la Vejiga Urinaria , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Hibridación Fluorescente in Situ , MicroARNs/genética , Estabilidad del ARN , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Vejiga Urinaria/genética
19.
Cancer Gene Ther ; 31(1): 82-93, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37945969

RESUMEN

The incidence and mortality rates of renal cell carcinoma (RCC) have rapidly increased worldwide. To gain new insights into the regulatory role of circular RNAs (circRNAs) in RCC progression, we conducted RNA sequencing on three pairs of ccRCC and adjacent normal tissues. RT-PCR was utilized to analyze RNA expression. We investigated the effects of circATG9A on RCC cells through various assays including CCK-8, Transwell, wound healing, and colony formation assays. Furthermore, we employed FISH, RNA pull-down, luciferase reporter, and RIP assays to elucidate the mechanism by which circATG9A regulates RCC. Ultimately, we identified 118 differentially expressed circRNAs in RCC, including a novel circRNA, circATG9A, which was found to promote RCC progression both in vitro and in vivo. Moreover, mRNA sequencing, western blotting, and rescue experiments indicated that TRPM3 is the target of circATG9A in RCC progression. Bioinformatic analysis, RNA pull-down, FISH, and RIP assays suggested that circATG9A regulates TRPM3 expression by acting as a sponge for miR-497-5p. Finally, Western blotting revealed that circATG9A promotes the epithelial-mesenchymal transition (EMT) process through the Wnt/ß-catenin signaling pathway. Our findings demonstrate that circATG9A is a novel circRNA upregulated in RCC that plays a crucial role in the EMT process through the miR-497-5p/TRPM3/Wnt/ß-catenin axis. These results suggest that circATG9A could be a promising target for RCC prognosis and therapy.


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , MicroARNs , Humanos , Carcinoma de Células Renales/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores , Neoplasias Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética
20.
J Res Adolesc ; 34(1): 127-140, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38013604

RESUMEN

This study aimed to examine the longitudinal reciprocal relationship between parental maltreatment and child bullying perpetration from middle childhood to early adolescence in China and the associated gender differences. Eight hundred ninety-one children completed a battery of questionnaires at four time points. A random-intercept cross-lagged model was established. The results indicated that at the between-person level, child bullying perpetration was positively associated with physical and psychological maltreatment. At the within-person level, there was a significant association between an increase in bullying perpetration and an increase in parental psychological and physical maltreatment across the four time points. Conversely, an increase in physical maltreatment led to an increase in child bullying perpetration from T1 to T2, while an increase in psychological maltreatment resulted in an increase in child bullying perpetration from T1 to T2 and T2 to T3. Furthermore, an increase in physical maltreatment increased boys' bullying perpetration but decreased that in girls from T2 to T3. These findings provide inspiration for future family education and anti-bullying interventions in schools.


Asunto(s)
Acoso Escolar , Masculino , Adolescente , Femenino , Humanos , Niño , Estudios Longitudinales , Acoso Escolar/psicología , Instituciones Académicas , Abuso Físico , Padres
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