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1.
Oncol Res ; 32(9): 1439-1452, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39220139

RESUMEN

Objectives: The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types; however, its precise role within the context of lung adenocarcinoma (LUAD) remains elusive. This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways. Methods: Utilizing bioinformatics methodologies, we explored the differential expression of NCAPD2 between normal and tumor samples, along with its correlations with clinical-pathological characteristics, survival prognosis, and immune infiltration. Results: In the TCGA-LUAD dataset, tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples (p < 0.001). Clinically, higher NCAPD2 expression was notably associated with advanced T, N, and M stages, pathologic stage, gender, smoking status, and diminished overall survival (OS). Moreover, differentially expressed genes (DEGs) associated with NCAPD2 were predominantly enriched in pathways related to cell division. Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells, naïve CD4+ T cells, activated memory CD4+ T cells, and M1 macrophages. In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cell cycle progression. Conclusions: In summary, NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Biomarcadores de Tumor , Ciclo Celular , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Humanos , Proliferación Celular/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/mortalidad , Pronóstico , Movimiento Celular/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Ciclo Celular/genética , Invasividad Neoplásica , Femenino , Masculino , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Biología Computacional/métodos
2.
Opt Lett ; 49(18): 5067-5070, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39270229

RESUMEN

The fabrication of anti-reflection (AR) subwavelength structures (SWSs) of lithium niobate (LN) is a challenging but rewarding task in mid-infrared LN laser systems. However, there are still some issues with the high-quality processing and fabrication of bifacial AR SWSs. Herein, a novel, to the best of our knowledge, approach to the fabrication of SWSs was proposed, which includes femtosecond laser ablation followed by wet etching and thermal annealing. The fabricated structures exhibit high surface quality (Ra = 0.08 nm) and uniformity. According to the experimental and simulated results, the transmittance of the mid-infrared AR SWSs with a period of 1.8 µm could be improved from 78% to 87% in the 3.6-5 µm band. Furthermore, the double-sided construction enabled a transmittance of up to 90%. The results have great potential in the promotion of the development of mid-infrared laser systems and LN-based photonics.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39206548

RESUMEN

Background: Despite single-incision laparoscopic surgery (SILS) being a standard procedure, its main shortcomings include narrow operating space and instrument collisions. Although the proposal of single-incision plus one-port laparoscopic surgery (SILS + 1) reduces the operational difficulty, laparoscopic pancreaticoduodenectomy (LPD) involves complex digestive tract resection and anastomosis. To reduce the number of incisions while ensuring the quality of LPD, we propose a single-incision plus two ports LPD (SILPD + 2) procedure wherein a surgeon uses two trocars with a traditional layout while the assistant and scope assistant conduct subumbilical incision. Methods: Retrospective analysis was performed of the perioperative data of 64 patients who underwent total LPD at our department from January to June 2023, including their age, gender, surgical operation time, estimated bleeding loss, and postoperative complications. Based on the number of inserted trocars, the patients were assigned to the conventional LPD (CLPD) group (n = 55) with five incisions and the new SILPD + 2 group (n = 9). Results: A total of 64 patients were included in this study, including 55 in the CLPD group and 9 in the SILPD + 2 group. The SILPD + 2 group patients had lower age and body mass index when compared to the CLPD group patients, albeit there was no statistical significance. In both groups of patients, laparoscopic surgery was completed. Regarding the operation time, estimated blood loss, and intraoperative blood transfusion, the SILPD + 2 group showed no significant disadvantage. Conclusion: When compared to CLPD, SILPD + 2 reduced the surgical difficulty by reducing incisions, and there was no significant difference in the short-term prognosis outcomes.

4.
CNS Neurosci Ther ; 30(7): e14863, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39036868

RESUMEN

OBJECTIVE: Childhood sensory abnormalities experience has a crucial influence on the structure and function of the adult brain. The underlying mechanism of neurological function induced by childhood sensory abnormalities experience is still unclear. Our study was to investigate whether the GABAergic neurons in the anterior cingulate cortex (ACC) regulate social disorders caused by childhood sensory abnormalities experience. METHODS: We used two mouse models, complete Freund's adjuvant (CFA) injection mice and bilateral whisker trimming (BWT) mice in childhood. We applied immunofluorescence, chemogenetic and optogenetic to study the mechanism of parvalbumin (PV) neurons and somatostatin (SST) neurons in ACC in regulating social disorders induced by sensory abnormalities in childhood. RESULTS: Inflammatory pain in childhood leads to social preference disorders, while BWT in childhood leads to social novelty disorders in adult mice. Inflammatory pain and BWT in childhood caused an increase in the number of PV and SST neurons, respectively, in adult mice ACC. Inhibiting PV neurons in ACC improved social preference disorders in adult mice that experienced inflammatory pain during childhood. Inhibiting SST neurons in ACC improved social novelty disorders in adult mice that experienced BWT in childhood. CONCLUSIONS: Our study reveals that PV and SST neurons of the ACC may play a critical role in regulating social disorders induced by sensory abnormalities in childhood.


Asunto(s)
Giro del Cíngulo , Ratones Endogámicos C57BL , Parvalbúminas , Somatostatina , Animales , Ratones , Somatostatina/metabolismo , Masculino , Parvalbúminas/metabolismo , Neuronas GABAérgicas/fisiología , Adyuvante de Freund/toxicidad , Vibrisas/fisiología , Vibrisas/inervación , Neuronas , Trastorno de la Conducta Social/etiología , Ratones Transgénicos
5.
FASEB J ; 38(14): e23833, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39012313

RESUMEN

Recurrent spontaneous abortion (RSA) is a common pregnancy-related disorder. Cbl proto-oncogene like 1 (CBLL1) is an E3 ubiquitin ligase, which has been reported to vary with the menstrual cycle in the endometrium. However, whether CBLL1 is involved in the occurrence and development of RSA remains unclear. This study aimed to investigate the effects of CBLL1 on RSA. We analyzed the expression of CBLL1 in the decidua of RSA patients, as well as its functional effects on cellular senescence, oxidative stress, and proliferation of human endometrial stromal cells (HESCs). RNA sequencing was employed to identify a key downstream target gene regulated by CBLL1. We found that CBLL1 was upregulated in the decidua of RSA patients. Additionally, overexpression of CBLL1 promoted HESC senescence, increased oxidative stress levels, and inhibited proliferation. Phosphatase and tensin homolog located on chromosome 10 (PTEN) was identified as one of the important downstream target genes of CBLL1. In vivo experiments demonstrated that CBLL1 overexpression in the endometrium caused higher embryo absorption rate in mice. Consequently, elevated CBLL1 expression is a potential cause of RSA, representing a novel therapeutic target for RSA.


Asunto(s)
Aborto Habitual , Senescencia Celular , Endometrio , Fosfohidrolasa PTEN , Células del Estroma , Adulto , Animales , Femenino , Humanos , Ratones , Embarazo , Aborto Habitual/metabolismo , Aborto Habitual/genética , Aborto Habitual/patología , Proliferación Celular , Decidua/metabolismo , Decidua/patología , Endometrio/metabolismo , Endometrio/patología , Estrés Oxidativo , Proto-Oncogenes Mas , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Células del Estroma/metabolismo
6.
Immunol Res ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39078518

RESUMEN

Our previous bioinformatics analysis has revealed that Rab-interacting lysosomal protein-like 2 (RILPL2) is associated with tumor immune microenvironment in non-small cell lung cancer (NSCLC). In our study, we collected 140 patients with primary NSCLC to verify the RILPL2 expression and its prognostic value, the relationship between RILPL2 expression and CD4+, CD8+T cell infiltration. A total of 140 patients who had been diagnosed with primary NSCLC (including 66 lung adenocarcinomas and 74 lung squamous cell carcinomas) were enrolled in our study. Immunohistochemical (IHC) staining was performed to analyze the expression of RILPL2, CD4, and CD8 in these patients. Compared with peri-cancer tissues, the RILPL2 expression in NSCLC tissues was significantly lower (P < 0.0001). RILPL2 expression was significantly related to clinical stage (P = 0.019), and low RILPL2 expression indicated higher stage. Low RILPL2 expression predicted worse overall survival (OS) in NSCLC patients (P = 0.017). Correlational analyses revealed that RILPL2 expression was significantly positively correlated with CD4+T cell infiltration in NSCLC (R = 0.294, P < 0.001), LUAD subgroup (R = 0.256, P = 0.038), and LUSC subgroup (R = 0.333, P = 0.004); RILPL2 expression was also significantly positively correlated with CD8+ T cell infiltration in NSCLC (R = 0.263, P = 0.002), LUAD subgroup (R = 0.280, P = 0.023), and LUSC subgroup (R = 0.250, P = 0.031). In conclusion, RILPL2 expression was downregulated in NSCLC; low RILPL2 expression was significantly related to higher stage and worse prognosis; RILPL2 expression was significantly positively correlated with CD4+, CD8+T cell infiltration.

7.
Colloids Surf B Biointerfaces ; 241: 113995, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38870647

RESUMEN

The interaction between nucleotide molecules and lipid molecules plays important roles in cell activities, but the molecular mechanism is very elusive. In the present study, a small but noticeable interaction between the negatively charged phosphatidylethanolamine (PE) and Guanosine monophosphate (GMP) molecules was observed from the PE monolayer at the air/water interface. As shown by the sum frequency generation (SFG) spectra and Pi-A isotherm of the PE monolayer, the interaction between the PE and GMP molecules imposes very small changes to the PE molecules. However, the Brewster angle microscopy (BAM) technique revealed that the assembly conformations of PE molecules are significantly changed by the adsorption of GMP molecules. By comparing the SFG spectra of PE monolayers after the adsorption of GMP, guanosine and guanine, it is also shown that the hydrogen bonding effect plays an important role in the nucleotide-PE interactions. These results provide fundamental insight into the structure changes during the nucleotide-lipid interaction, which may shed light on the molecular mechanism of viral infection, DNA drug delivery, and cell membrane curvature control in the brain or neurons.


Asunto(s)
Guanosina Monofosfato , Fosfatidiletanolaminas , Fosfatidiletanolaminas/química , Guanosina Monofosfato/química , Guanosina Monofosfato/metabolismo , Adsorción , Propiedades de Superficie , Microscopía , Enlace de Hidrógeno , Agua/química
8.
Artículo en Inglés | MEDLINE | ID: mdl-38862424

RESUMEN

The order Acipenseriformes, which includes sturgeons and paddlefishes, represents "living fossils" with complex genomes that are good models for understanding whole-genome duplication (WGD) and ploidy evolution in fishes. Here, we sequenced and assembled the first high-quality chromosome-level genome for the complex octoploid Acipenser sinensis (Chinese sturgeon), a critically endangered species that also represents a poorly understood ploidy group in Acipenseriformes. Our results show that A. sinensis is a complex autooctoploid species containing four kinds of octovalents (8n), a hexavalent (6n), two tetravalents (4n), and a divalent (2n). An analysis taking into account delayed rediploidization reveals that the octoploid genome composition of Chinese sturgeon results from two rounds of homologous WGDs, and further provides insights into the timing of its ploidy evolution. This study provides the first octoploid genome resource of Acipenseriformes for understanding ploidy compositions and evolutionary trajectories of polyploid fishes.


Asunto(s)
Evolución Molecular , Peces , Genoma , Poliploidía , Secuenciación Completa del Genoma , Animales , Peces/genética , Secuenciación Completa del Genoma/métodos , Genoma/genética , Filogenia
9.
Biometrics ; 80(2)2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38837902

RESUMEN

In mobile health, tailoring interventions for real-time delivery is of paramount importance. Micro-randomized trials have emerged as the "gold-standard" methodology for developing such interventions. Analyzing data from these trials provides insights into the efficacy of interventions and the potential moderation by specific covariates. The "causal excursion effect," a novel class of causal estimand, addresses these inquiries. Yet, existing research mainly focuses on continuous or binary data, leaving count data largely unexplored. The current work is motivated by the Drink Less micro-randomized trial from the UK, which focuses on a zero-inflated proximal outcome, i.e., the number of screen views in the subsequent hour following the intervention decision point. To be specific, we revisit the concept of causal excursion effect, specifically for zero-inflated count outcomes, and introduce novel estimation approaches that incorporate nonparametric techniques. Bidirectional asymptotics are established for the proposed estimators. Simulation studies are conducted to evaluate the performance of the proposed methods. As an illustration, we also implement these methods to the Drink Less trial data.


Asunto(s)
Simulación por Computador , Telemedicina , Humanos , Telemedicina/estadística & datos numéricos , Estadísticas no Paramétricas , Causalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Modelos Estadísticos , Biometría/métodos , Interpretación Estadística de Datos
10.
Polymers (Basel) ; 16(11)2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38891496

RESUMEN

Dielectric elastomer is a kind of electronic electroactive polymer, which plays an important role in the application of soft robots and flexible electronics. In this study, an all-organic polyaniline/copper phthalocyanine/silicone rubber (PANI/CuPc/PDMS) dielectric composite with superior comprehensive properties was prepared by manipulating the arrangement of filler in a polymer matrix assisted by electric fields. Both CuPc particles and PANI particles can form network structures in the PDMS matrix by self-assembly under electric fields, which can enhance the dielectric properties of the composites at low filler content. The dielectric constant of the assembled PANI/CuPc/PDMS composites can reach up to 140 at 100 Hz when the content of CuPc and PANI particles is 4 wt% and 2.5 wt%, respectively. Moreover, the elastic modulus of the composites remains below 2 MPa, which is important for electro-deforming. The strain of assembled PANI/CuPc/PDMS three-phase composites at low electric field strength (2 kV/mm) can increase up to five times the composites with randomly dispersed particles, which makes this composite have potential application in the field of soft robots and flexible electronics.

11.
Org Lett ; 26(24): 5136-5140, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38847357

RESUMEN

Herein, we report a rhodium-catalyzed C-H activation/[4+2] cyclization reaction between α,ß-unsaturated amides and iodonium ylides for the synthesis of novel 7,8-dihydroquinoline-2,5-diones and analogues. This protocol provides a series of pyridones fused with saturated cycles with good functional group compatibility, good water and air tolerance, and good to excellent yields under mild and green reaction conditions. Additionally, scale-up synthesis can be smoothly performed with as low as 0.25 mol % catalyst loading. Recycling experiments and different transformation experiments were also carried out to demonstrate the potential synthetic utility of this protocol.

12.
Biol Reprod ; 111(2): 448-462, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38780057

RESUMEN

Inappropriate endometrial stromal decidualization has been implied as an important reason of many pregnancy-related complications, such as unexplained recurrent spontaneous abortion, preeclampsia, and intrauterine growth restriction. Here, we observed that thrombospondin-1, an adhesive glycoprotein, was significantly downregulated in endometrial decidual cells from patients with unexplained recurrent spontaneous abortion. The immortalized human endometrial stromal cell line was used to investigate the possible THBS1-mediated regulation of decidualization. In vitro experiments found that the expression level of THBS1 increased with the normal decidualization process. Knockdown of THBS1 could decrease the expression levels of prolactin and insulin-like growth factor binding protein-1, two acknowledged human decidualization markers, whereas THBS1 overexpression could reverse these effects. The RNA sequencing results demonstrated that the extracellular regulated protein kinases signaling pathway was potentially affected by the knockdown of THBS1. We further confirmed that the regulation of THBS1 on decidualization was achieved through the ERK signaling pathway by the treatment of inhibitors. Moreover, knockdown of THBS1 in pregnant mice could impair decidualization and result in an increased fetus resorption rate. Altogether, our study demonstrated a crucial role of THBS1 in the pathophysiological process of unexplained recurrent spontaneous abortion and provided some new insights into the research of pregnancy-related complications.


Asunto(s)
Aborto Habitual , Decidua , Endometrio , Células del Estroma , Trombospondina 1 , Adulto , Animales , Femenino , Humanos , Ratones , Embarazo , Aborto Habitual/genética , Aborto Habitual/metabolismo , Decidua/metabolismo , Endometrio/metabolismo , Endometrio/patología , Células del Estroma/metabolismo , Trombospondina 1/genética , Trombospondina 1/metabolismo , Masculino
13.
Front Nutr ; 11: 1389745, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689937

RESUMEN

Background: Bread wheat is one of the most important food crops associated with ensuring food security and human nutritional health. The starch quality is an important index of high-quality wheat. It is affected by a complex series of factors; among which, suitable sowing time is a key factor. Aim and methods: To analyze the integrative effects of sowing time on the starch quality of high-quality wheat, in the present study, we selected a high-quality bread wheat cultivar Jinan 17 and investigated the effect of different sowing times on the starch properties and the related genes by analyzing X-ray diffraction patterns, apparent amylose content, thermal properties, pasting properties, in vitro starch digestibility, and qRT-PCR. Meanwhile, we also investigated the agronomic and yield performance that may be associated with the starch properties. Results: Delayed sowing had little effect on starch crystalline morphology, but there was a tendency to reduce the formation of crystals within wheat starch granules: (1) delayed sowing for 15 days altered the thermal properties of starch, including onset, peak and termination temperatures, and enthalpy changes; (2) delayed sowing for 30 days changed the thermal characteristics of starch relatively insignificant; (3) significant differences in pasting characteristics occurred: peak viscosity and hold-through viscosity increased, while final viscosity, breakdown viscosity, and setback viscosity tended to increase and then decrease, suggesting that delayed sowing caused changes in the surface of the starch granules resulting in a decrease in digestibility. Analysis of related genes showed that several key enzymes in starch biosynthesis were significantly affected by delayed sowing, leading to a reduction in apparent straight-chain starch content. In addition to starch properties, thousand-kernel weight also increased under delayed sowing conditions compared with normal sowing. Conclusion: The impact of delayed sowing on starch quality is multifaceted and complex, from the fine structure, and functional properties of the starch to the regulation of key gene expression. Our study holds significant practical value for optimizing wheat planting management and maximizing the potential in both quality and yield.

14.
Front Plant Sci ; 15: 1387427, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817928

RESUMEN

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durumDesf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulks were annotated and analyzed by Gene Ontology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew.

15.
Brain Behav ; 14(5): e3529, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38747741

RESUMEN

BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.


Asunto(s)
Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Anciano , Persona de Mediana Edad , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Imagen por Resonancia Magnética , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/epidemiología , Úlcera/patología
16.
J Nanobiotechnology ; 22(1): 242, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735936

RESUMEN

BACKGROUND: Two-dimensional ultrathin Ti3C2 (MXene) nanosheets have gained significant attention in various biomedical applications. Although previous studies have described the accumulation and associated damage of Ti3C2 nanosheets in the testes and placenta. However, it is currently unclear whether Ti3C2 nanosheets can be translocated to the ovaries and cause ovarian damage, thereby impairing ovarian functions. RESULTS: We established a mouse model with different doses (1.25, 2.5, and 5 mg/kg bw/d) of Ti3C2 nanosheets injected intravenously for three days. We demonstrated that Ti3C2 nanosheets can enter the ovaries and were internalized by granulosa cells, leading to a decrease in the number of primary, secondary and antral follicles. Furthermore, the decrease in follicles is closely associated with higher levels of FSH and LH, as well as increased level of E2 and P4, and decreased level of T in mouse ovary. In further studies, we found that exposure toTi3C2 nanosheets increased the levels of Beclin1, ATG5, and the ratio of LC3II/Ι, leading to autophagy activation. Additionally, the level of P62 increased, resulting in autophagic flux blockade. Ti3C2 nanosheets can activate autophagy through the PI3K/AKT/mTOR signaling pathway, with oxidative stress playing an important role in this process. Therefore, we chose the ovarian granulosa cell line (KGN cells) for in vitro validation of the impact of autophagy on the hormone secretion capability. The inhibition of autophagy initiation by 3-Methyladenine (3-MA) promoted smooth autophagic flow, thereby partially reduced the secretion of estradiol and progesterone by KGN cells; Whereas blocking autophagic flux by Rapamycin (RAPA) further exacerbated the secretion of estradiol and progesterone in cells. CONCLUSION: Ti3C2 nanosheet-induced increased secretion of hormones in the ovary is mediated through the activation of autophagy and impairment of autophagic flux, which disrupts normal follicular development. These results imply that autophagy dysfunction may be one of the underlying mechanisms of Ti3C2-induced damage to ovarian granulosa cells. Our findings further reveal the mechanism of female reproductive toxicity induced by Ti3C2 nanosheets.


Asunto(s)
Autofagia , Células de la Granulosa , Nanoestructuras , Ovario , Titanio , Animales , Femenino , Autofagia/efectos de los fármacos , Titanio/toxicidad , Titanio/química , Titanio/farmacología , Ratones , Ovario/efectos de los fármacos , Ovario/metabolismo , Nanoestructuras/química , Células de la Granulosa/efectos de los fármacos , Células de la Granulosa/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo
17.
Front Med (Lausanne) ; 11: 1338947, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633306

RESUMEN

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

18.
Heliyon ; 10(8): e29352, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38644837

RESUMEN

Background and objective: The association between cardiac dysfunction and functional outcome in acute ischemic stroke (AIS) is not clear. We aimed to investigate the relationship between the routinely assessed left ventricular ejection fraction (LVEF) and functional outcomes in patients with AIS. Methods: Data came from a prospective, observational, single-center study (Effect of Cardiac Function on Short-term Functional Prognosis in Patients with Acute Ischemic Stroke, SPARK). The LVEF was assessed with transthoracic echocardiography within 7 days of stroke onset. The primary outcome was functional disability, defined as a modified Rankin Scale score of 3-6 at 90 days (range: 0-6, with higher scores indicating greater disability). We also investigated the association of the LVEF with mortality, early neurological deterioration, hospital stay, and costs. Multivariate logistic regression analysis and 2:1 propensity score matching (PSM) were performed to compare the differences in outcomes. Results: A total of 1181 patients were included in this analysis, of which 87 (7.4 %) patients were found to have LVEF of <60 %. In the entire study population, LVEF<60 % was significantly associated with functional disability at 90 days (odds ratio [OR]: 1.85, 95 % confidence intervals (CI): 1.01-3.40) after adjusting for all confounders. After PSM, the association was consistently significant (OR: 5.32, 95 % CI: 3.04-9.30). However, associations of the LVEF with mortality, early neurological deterioration, hospital stay, and costs were not consistently significant across all analyses. In the subgroup analysis, the association of LVEF of <60 % with functional disability was statistically significant in patients with non-cardioembolic stroke, but not in patients with cardioembolic stroke (P for interaction = 0.872). Conclusions: An LVEF of <60 % will likely increase the risk of functional disability in patients with AIS. Future strategies to prevent cardiac dysfunction in the acute phase are needed.

19.
Front Cell Dev Biol ; 12: 1369091, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38601082

RESUMEN

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.

20.
Front Endocrinol (Lausanne) ; 15: 1354577, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38577568

RESUMEN

Introduction: Osteoporosis, a disease of reduced bone mass and microstructural deterioration leading to fragility fractures, is becoming more prevalent as aging progresses, significantly increasing the socioeconomic burden. In past studies, there has been a growing awareness of the harmful effects of heavy metals on bone, with cadmium being a significant exposure factor. The purpose of this study was to look into the association between adult bone mineral density(BMD) and blood cadmium levels. Methods: Based on information from the 2013-2014, 2017-2018 NHANES, weighted multiple regression, generalized weighted modeling, and smoothed curve fitting were utilized to investigate the association between blood cadmium and femur BMD. Furthermore, subgroup analyses were conducted to investigate any differences in the associations between age, sex, race, chronic kidney disease, and diabetes. Results: In 2,146 participants, blood cadmium levels and total femur [-0.02 (-0.03, -0.01), 0.0027], femoral neck [-0.01 (-0.02, -0.00), 0.0240], femoral trochanter [-0.01 (-0.02, -0.00), 0.0042], and intertrochanteric femoral trochanter [-0.02 (-0.03, -0.00), 0.0101] BMD were negatively correlated. Subgroup analyses showed that this association was more pronounced in women, non-Hispanic white people and other Hispanics, and those with chronic kidney disease and diabetes. Our results pointed to a negative relationship between femoral BMD and blood cadmium. This negative association varied by age, sex, race, diabetes, and chronic kidney disease. In particular, bone mineral density was more significantly negatively affected by blood cadmium levels in groups with diabetes and chronic kidney disease. Conclusion: Our findings demonstrated a significant negative association between blood cadmium levels and bone mineral density in a population of U.S. adults.


Asunto(s)
Diabetes Mellitus , Insuficiencia Renal Crónica , Adulto , Humanos , Femenino , Densidad Ósea , Estudios Transversales , Cadmio , Encuestas Nutricionales
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