The Kaohsiung journal of medical sciences最新文献

Intrauterine adhesion (IUA) is the second most common cause of secondary infertility in women and can also lead to menstrual abnormalities and multiple adverse pregnancy outcomes. Therefore, elucidating the mechanism of its development is crucial for the prevention and treatment of IUA. This study will investigate the function and mechanism of forkhead box P1 (FOXP1)/DNA methyltransferase 1 (DNMT1)/unc-51-like autophagy activating kinase 1 (ULK1) in IUA. Expression levels of key genes were detected using western blot and quantitative - real time reverse transcription polymerase chain reaction. Cell proliferation was detected by CCK-8 and EdU staining. Transcriptional regulation relationships were detected by dual luciferase reporter gene and chromatin immunoprecipitation (ChIP) assay. Methylation station of ULK1 was detected by methylmion specific PCR (MSP). Fibrosis and pathological changes in the uterine cavity tissues were detected by Masson and hematoxylin and eosin staining. It was observed that the expression of FOXP1 and DNMT1 increased in transforming growth factor (TGF)-β1-induced cells, while ULK1 expression decreased. Downregulation of FOXP1 could inhibit human endometrial stromal cells proliferation and autophagy, as well as decrease the expression of fibrogenic factors (collagen type I alpha 1 chain [COL1A1], fibronectin [FN], and alpha-smooth muscle actin [α-SMA]). The results of MSP and ChIP experiments showed that DNMT1 promotes methylation of the ULK1 promoter region and inhibits its transcription. In an animal model, knockdown of FOXP1 alleviated pathological fibrosis and uterine adhesions. Knockdown of FOXP1 can inhibit endometrial fibrosis in IUA rats; FOXP1 could be a potential target for the treatment of IUA.

Diabetes-induced cognitive dysfunction (DCD) is a neurological disorder associated with diabetes, characterized by cognitive impairment driven by neuronal injury from chronic high glucose (HG) exposure. This study aims to elucidate the role and mechanisms of the X-linked inhibitor of apoptosis protein (XIAP)/thioredoxin-interacting protein (TXNIP) in hippocampal neuron cell death and cognitive function within DCD models. A diabetic rat model was established using a high-fat/sucrose diet and streptozotocin injection. Primary hippocampal neurons were stimulated with HG to mimic diabetic conditions. Cognitive and memory functions were assessed using the Morris water maze (MWM) and novel object recognition test (ORT).

Metabolic-associated fatty liver disease (MAFLD) induced-severe hepatic steatosis poses significant health risks. Early prediction of this condition is crucial for prompt intervention. Short-chain fatty acids (SCFAs) and tryptophan are gut metabolites correlated with MAFLD pathogenesis in the gut-liver axis. This study aims to construct prediction models for severe hepatic steatosis by including SCFAs and tryptophan metabolites. This study enrolled 83 participants from the outpatient department in 2023. Physical measurements, serum metabolic and inflammatory markers, metabolites of serum SCFAs and tryptophan were collected. Severe hepatic steatosis was diagnosed using vibration-controlled transient elastography and abdominal sonography. All 40 (48.2%) participants diagnosed with severe hepatic steatosis had MAFLD, while approximately three-quarters of those without severe hepatic steatosis had MAFLD. In comparison to the non-severe hepatic steatosis group, individuals with severe hepatic steatosis exhibited higher levels of waist and arm circumference, serum triglyceride (TG), and lower levels of serum high-density lipoprotein cholesterol (HDL-C) and AST/ALT ratio. They also had higher serum levels of lipopolysaccharide-binding protein, isovaleric acid, and propionic acid, and lower levels of 3-methylvaleric acid, indole-3-propionic acid, and indoxyl sulfate. Models incorporating these markers predicted severe hepatic steatosis. One model additionally included waist circumference and triglyceride-glucose index, while the other incorporated arm circumference and TG/HDL-C ratio. The area under the curve reached 0.958 and 0.938, respectively (p < 0.001). SCFAs and tryptophan metabolites are valuable in predicting severe hepatic steatosis. Further research is needed to investigate the roles of these metabolites in MAFLD.

Patients with chronic migraine (CM) often exhibit structural and functional alterations in pain-matrix regions, but it remains unclear how preventive treatment affects these changes. Therefore, this study aimed to investigate the structural and functional changes in pain-matrix regions in CM patients after 6-month treatment. A total of 24 patients with CM and 15 healthy controls were recruited for this study. Patients were divided into responder group (N = 9) and non-responder group (N = 15). After completing the Migraine Disability Assessment (MIDAS) questionnaire, all patients underwent whole-brain high-resolution T1-weighted images, diffusion-weighted imaging, and resting-state functional magnetic resonance imaging at baseline and 6-month follow-up. Whole brain gray matter volume and white matter diffusion indices were analyzed using voxel-based analysis. Structural and functional connectivity analyses were performed to understand brain changes in patients after 6-month preventive treatment. The responder group exhibited significantly higher MIDAS scores than the non-responder group at baseline, but no significant difference between the two groups at follow-up. No significant interval change was noted in gray matter volume, white matter diffusion indices, and structural connectivity in CM patients after 6-month treatment. Nonetheless, the functional connectivity was significantly increased between occipital, temporal lobes and cerebellum, and was significantly decreased between parietal and temporal lobes after 6-month preventive treatment. We concluded that resting-state functional connectivity was suitable for investigating the preventive treatment effect on CM patients.

Retinoblastoma (RB) poses significant challenges in clinical management due to the emergence of resistance to conventional chemotherapeutic agents, particularly carboplatin (CBP). In this study, we investigated the molecular mechanisms underlying CBP resistance in RB, with a focus on the role of autophagy and the influence of ubiquitin-specific peptidase 49 (USP49). We observed upregulation of USP49 in RB tissues and cell lines, correlating with disease progression. Functional assays revealed that USP49 promoted aggressive proliferation and conferred CBP resistance in RB cells. Furthermore, USP49 accelerated tumor growth and induced CBP resistance in vivo. Mechanistically, we found that USP49 facilitated CBP resistance by promoting autophagy activation. In addition, we identified insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)-mediated N6-methyladenosine (m⁶A) modification of USP49 as a regulatory mechanism, wherein IGF2BP3 upregulated USP49 expression in an m⁶A-dependent manner. Moreover, USP49 stabilized SIRT1, a protein associated with CBP resistance and autophagy, by inhibiting its ubiquitination and degradation. Rescue experiments confirmed the pivotal role of SIRT1 in USP49-mediated CBP resistance. Our findings delineate a novel molecular network involving USP49-mediated autophagy in promoting CBP resistance in RB, offering potential targets for therapeutic intervention to enhance treatment efficacy and improve outcomes for RB patients.

Nuciferine (NCF) is a bioactive compound from lotus leaves and has been proven to prevent osteoclastogenesis and ovariectomy-induced osteoporosis by our previous research. However, the underlying mechanism is still unclear. In this research, Raw264.7 cells were induced into osteoclast with or without NCF. CCK-8 and Edu assays were performed to detect the effects of 30 μM NCF on cell viability and proliferation. TRAP staining and bone resorption assays were performed to observe the role of NCF in osteoclastogenesis and bone resorption. RT-PCR and Western blot were performed to detect the effects of NCF on osteoclast-related genes, glycolysis-related genes, and reactive oxygen species (ROS)-related genes. Seahorse assays, lactate concentration and glucose consumption were performed to observe cell metabolism change. DCFH-DA fluorescent probe was used to detect ROS level. In this work, 30 μM NCF could not influence cell viability and cell proliferation. Osteoclast differentiation could be inhibited by 30 μM NCF. Bone resorption assay could also observe that bone resorption ability was successfully inhibited by 30 μM NCF. In seahorse assay, we discovered that NCF could decrease extracellular acid rate and increase oxygen consumption. RT-PCR and Western blot results showed that NCF could decrease the expression of hexokinase2, pyruvate kinase muscle 2, and lactate dehydrogenase A and that NCF could also weaken the concentration of lactate. However, pyruvate kinase muscle 2 activator (GC69716) and lactate addition could promote osteoclastogenesis and bone resorption and promote the expression of c-Fos and nuclear factor of activated T cells c1. Besides, NCF could also inhibit the production of ROS. In conclusion, NCF might inhibit osteoclast formation through inhibiting glycolysis metabolism and ROS production.