Current Medical Science最新文献

Objective: The objective of this study was to explore the therapeutic effects of kaempferol (Kae) on rheumatoid arthritis (RA) and to elucidate the underlying mechanisms.

Methods: The collagen-induced arthritis (CIA) model was established using collagen II to induce RA. Mice were treated with Kae at a dose of 25 or 50 mg/kg/day via gavage. Pathological changes in the ankle joint were analyzed. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of inflammatory factors. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to assess the expression of genes associated with the balance of regulatory T (Treg)/T helper 17 (Th17) cells. Flow cytometry was utilized to determine the Treg/Th17 ratio. Furthermore, these techniques were employed to evaluate the impact of miR-34a and Foxp3 dysregulation on cellular functions in RA under the influence of Kae. Dual luciferase reporter assay was conducted to analyze the binding of miR-34a to Foxp3.

Results: Treatment with Kae led to a downregulation of receptor-related orphan receptor gamma t (RORγt) and IL-17 expression, and an upregulation of Foxp3, IL-10, and TGF-β expression in CIA mice. Kae intervention inhibited the production of proinflammatory cytokines and increased the production of anti-inflammatory cytokines. Furthermore, Kae treatment suppressed the expression of miR-34a, which was identified as a target of miR-34a. Finally, Kae regulated Treg/ Th17 balance-related genes and cellular inflammation through the miR-34a/Foxp3 axis.

Conclusion: The study demonstrated that Kae effectively ameliorates CIA in mice by modulating the Treg/Th17 balance and related genes via the miR-34a/Foxp3 axis. These findings suggest that Kae may serve as a promising therapeutic agent for the treatment of RA and for restoring immune homeostasis.

Objective: Alternative splicing affects gene expression during placental development. The present study aimed to identify poly (ADP-ribose) polymerase 1 (PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.

Methods: Decidual tissues were collected from women with induced abortion and spontaneous abortion. PARP1 transcription was quantified by RT-qPCR. Small interfering RNA (siRNA) was used to knock down the PARP1 expression in HTR-8/Svneo cells. The transfection efficiency was verified by RT-qPCR and Western blotting. Total RNA was extracted, and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes. The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR. Functional analysis, which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, was performed.

Results: The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group, when compared to the induced abortion group. However, the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells. Furthermore, 227 genes that underwent alternative splicing were identified, and these were differentially expressed in siPARP1 cells, when compared to siNC cells.

Conclusion: The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts. Furthermore, the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.

Objective: Our research aims to evaluate the diagnostic accuracy of colposcopy-guided biopsy (CGB) in detecting high-grade cervical lesions and explore how human papilloma virus (HPV) integration status and other factors affect its performance.

Methods: A retrospective cohort analysis involving 550 patients was conducted to evaluate whether the HPV integration plays a role in identifying high-grade cervical lesions and cervical cancer. Logistic regression models and area under the curve (AUC) calculations were employed.

Results: Our findings revealed that 53.5% of CGB/surgery pairs demonstrated congruent diagnoses, whereas 17.1% showed underestimation and 29.5% overestimation. Furthermore, multivariate logistic regression analysis identified several key predictors for cervical intraepithelial neoplasia (CIN)2+ and CIN3+ according to surgical pathology. Notably, a CGB confirming CIN2+ [odds ratio (OR)=6.0, 95% confidence interval (CI): 3.9-9.1, P<0.001], high-grade cytology (OR=2.6, 95% CI: 1.4-1.9, P=0.003), and HPV integration positivity (OR=2.2, 95% CI: 1.3-3.5, P<0.001) emerged as significant factors for CIN2+. Similarly, for CIN3+ identification, CGB confirming CIN2+ (OR=5.3, 95% CI: 3.4-8.3, P<0.001), high-grade cytology (OR=2.6, 95% CI: 1.5-4.7, P=0.001), and HPV integration positivity (OR=2.0, 95% CI: 1.3-3.1, P=0.003) were independent predictors.

Conclusion: Our study highlights the innovative role of HPV integration testing as a pivotal adjunct to CGB and cytology, offering a comprehensive approach that may enhance the diagnostic precision for high-grade cervical lesions, ultimately achieving more precise management strategies.

Objective: To investigate whether cardiac mast cells (MCs) participate in pressure overload-induced myocardial hypertrophy through the regulation of transient receptor potential vanilloid 4 (TRPV4).

Methods: Pressure overload-induced myocardial hypertrophy was induced via abdominal aortic constriction (AAC). Myocardial hypertrophy was evaluated by measuring the heart weight index (HW/BW), lung weight index (LW/BW), ratio of heart weight to tibia length (HW/TL), ratio of lung weight to tibia length (LW/TL), and cross-sectional area of myocardial cells. qRT-PCR was used to detect the mRNA expression of TRPV4. Western blotting was used to detect the protein expression of TRPV4, mast cell tryptase, myosin heavy chain beta (β-MHC), calcineurin A (CnA), and nuclear factor of activated T-cell c3 (NFATc3). ELISA was used to measure the levels of brain natriuretic peptide (BNP) and histamine. Fluo4 AM was used to detect the calcium signal in H9c2 myocardial cells.

Results: Compared with those of the sham rats, the myocardial mast cells, tryptase, HW/BW, LW/BW, HW/TL, and LW/TL, the cross-sectional area of the myocardial cells, and the expression of β-MHC, TRPV4, CnA, and NFATc3 in the myocardial tissue and the serum BNP of the AAC-treated rats increased significantly, whereas the MC stabilizer cromolyn sodium (CS) reversed these indicators. In H9c2 cardiomyocytes, treatment with histamine and the TRPV4 agonist GSK1016790A upregulated the expression of TRPV4, β-MHC, BNP, CnA and NFATc3 and increased calcium ion influx, whereas these effects were inhibited by the H2 receptor inhibitor famotidine and the TRPV4 inhibitor HC067047.

Conclusion: Cardiac MCs participate in pressure overload-induced myocardial hypertrophy through the upregulation of TRPV4 via its mediator histamine, and the Ca²⁺/CnA/NFATc3 signaling pathway is involved in this process.

Objective: Behavioral interventions have been shown to ameliorate the electroencephalogram (EEG) dynamics underlying the behavioral symptoms of autism spectrum disorder (ASD), while studies have also demonstrated that mirror neuron mu rhythm-based EEG neurofeedback training improves the behavioral functioning of individuals with ASD. This study aimed to test the effects of a wearable mu rhythm neurofeedback training system based on machine learning algorithms for children with autism.

Methods: A randomized, placebo-controlled study was carried out on 60 participants aged 3 to 6 years who were diagnosed with autism, at two center-based intervention sites. The neurofeedback group received active mu rhythm neurofeedback training, while the control group received a sham neurofeedback training. Other behavioral intervention programs were similar between the two groups.

Results: After 60 sessions of treatment, both groups showed significant improvements in several domains including language, social and problem behavior. The neurofeedback group showed significantly greater improvements in expressive language (P=0.013) and cognitive awareness (including joint attention, P=0.003) than did the placebo-controlled group.

Conclusion: Artificial intelligence-powered wearable EEG neurofeedback, as a type of brain-computer interface application, is a promising assistive technology that can provide targeted intervention for the core brain mechanisms underlying ASD symptoms.

Artificial intelligence (AI) is an interdisciplinary field that combines computer technology, mathematics, and several other fields. Recently, with the rapid development of machine learning (ML) and deep learning (DL), significant progress has been made in the field of AI. As one of the fastest-growing branches, DL can effectively extract features from big data and optimize the performance of various tasks. Moreover, with advancements in digital imaging technology, DL has become a key tool for processing high-dimensional medical image data and conducting medical image analysis in clinical applications. With the development of this technology, the diagnosis of orthopedic diseases has undergone significant changes. In this review, we describe recent research progress on DL in fracture diagnosis and discuss the value of DL in this field, providing a reference for better integration and development of DL technology in orthopedics.

Objective: Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM.

Methods: The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment.

Results: At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant.

Conclusion: QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.

Sepsis is a secondary condition resulting from severe systemic infections. It is a significant contributor to mortality in critically ill patients with rapid onset and severe symptoms. Acupuncture is a traditional Chinese medical treatment. Recent clinical studies have demonstrated that acupuncture, as an important synergistic therapy, has promising therapeutic effects in the treatment of sepsis. This paper reviews the mechanisms of immunomodulation and target organ protection associated with acupuncture and synergistic drug acupuncture in the treatment of sepsis. It also integrates existing studies to elucidate the modulation of the immune system and the protective effect of acupuncture on target organs.

Objective: Imbalances in liver lipid metabolism and inflammatory reactions driven by oxidized lipid deposition in blood vessels constitute the core of atherosclerosis. Insufficient degradation of cholesterol in the liver promotes oxidative modification of lipid particles and their deposition on the blood vessel wall in the peripheral circulation. The blood vessel wall engulfs and processes oxidized low-density lipoprotein (Ox-LDL) as foreign matter through pattern recognition receptors, ultimately forming lipid-encapsulated plaques. Among them, endothelial cell oxidized low density lipoprotein receptor 1 (LOX1) phagocytosis is an important link in initiating and promoting this mechanism, and hepatocytes, which are the core of lipid metabolism, are unable to process oxidized lipid particles because of the lack of receptors for the uptake of Ox-LDL. The objective of this study was to investigate whether continuous clearance of Ox-LDL through the liver metabolic pathway could provide better protection against statins therapy.

Methods: This study used statins combined with an adeno-associated virus (AAV8-TBG-LOX-1) liver-specific transfection system developed by our research group, in which statins reduced the level of LDL and promoted the ectopic expression of LOX-1 in hepatocytes to clear the continuous production of Ox-LDL. An ApoE knockout mouse model was used to study the effects of virus transfection and liver uptake and degradation of Ox-LDL. Laser confocal detection, Oil red staining and immunofluorescence staining were used to observe the effects of combined therapy on anti-atherosclerotic lesions.

Results: Laser confocal microscopy revealed that the recombinant viral vector AAV8-TBG-LOX-1 could specifically transfect hepatocytes and express LOX-1, which mediate hepatocyte phagocytosis and clearance of Ox-LDL. Oil red O staining of the aorta and valvular ring suggested that statins combined with AAV8-TBG-LOX-1 significantly inhibited atherosclerotic lesions. Tissue immunofluorescence staining suggested that statins could reduce the aggregation of macrophages in plaques and that combined therapy could further reduce the aggregation of macrophages in plaques.

Conclusion: Statins combined with AAV8-TBG-LOX-1 can alleviate the inflammatory response driven by lipids in the vascular wall, reduce the deposition of macrophages in plaques and inhibit atherosclerosis.

Objective: Menstrual blood-derived stem cells from endometriosis patients (E-MenSCs) have different gene expression patterns than those from healthy nonendometriotic females (NE-MenSCs). Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases. This study aimed to compare the effects of exosomes derived from NE-MenSCs (C-exos) and those from the roots of ginger (P-exos) on E-MenSCs.

Methods: E-MenSCs at the third passage were used, and after evaluating the effective dosage with MTT, C-exos (200 µg/mL) or P-exos (100 µg/mL) were added to treat them. Following a 72-h incubation, the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate. Also, genes related to inflammation (IL-6, IL-8, IL-1β, NF-κB, COX2), cell cycle (Cyclin D1), the steroid pathway (ESR1), migration and invasion (MMP-2, MMP-9, VEGF), and the apoptosis pathway (BAX, BCL2) were detected by real-time PCR.

Results: Apoptosis was increased in both the P- and C-exos groups. The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group. The expression levels of IL-8, NF-κB, COX-2, and MMP-9 were significantly decreased in both the P-exos group and the C-exos group. The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group. The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.

Conclusion: In this study, we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells. Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells. Considering that plant exosomes are easier to access and less expensive, they can be considered for clinical use in improving the symptoms of endometriosis patients.