Discovery medicine最新文献

Background: Age-related macular degeneration (AMD) is a significant factor causing blindness in adults. However, the clinical diagnosis of AMD is relatively challenging, due to the shortcomings of the existing clinical examination methods and the latent period of retinal damage before macular degeneration becomes apparent. This study aims to explore the potential of extracellular vesicles (EVs) protein chips for early diagnosis of AMD using patients' plasma samples.

Methods: To achieve early diagnosis of AMD, this study utilized a high-throughput platform for liquid biopsy based on EVs protein chips. Forty AMD patients and 41 normal individuals were recruited. Through machine learning methods, we identified that ATP-binding cassette transporter A1 (ABCA1) is an EVs protein marker for diagnosing AMD. Additionally, a validation set was constructed using the random forest method for verification.

Results: The results of the study indicated that ABCA1 is a reliable biomarker for diagnosing AMD. The validation using the random forest method confirmed the robustness and reliability of ABCA1 as a diagnostic marker. This finding suggested that ABCA1 can serve as a new promising liquid biopsy-based marker for diagnosing macular degeneration.

Conclusion: The utilization of EVs protein chips, combined with machine learning methods, can effectively identify ABCA1 as a biomarker for the early diagnosis of AMD. This approach offers a promising new method for liquid biopsy diagnostics, potentially improving the clinical diagnosis and management of macular degeneration.

Backgrounds: Recent studies have proven the oncogenic role of kinesin family member 20A (KIF20A) in several cancers. Tumor-associated macrophages (TAMs) were reported to participate in tumor initiation and metastasis. In this study, we aimed to explore the detailed mechanism underlying KIF20A in regulating the progression of ovarian cancer and its involvement with TAMs.

Methods: KIF20A and phosphatase and tensin homolog (PTEN) levels were assessed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-2'-deoxyuridine (EdU) staining assay, colony formation assay, flow cytometry, and western blot were employed to evaluate cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT). The relationship between KIF20A and PTEN was validated using a dual-luciferase assay. M2 macrophage polarization was verified by detecting their markers using RT-qPCR. THP-1 cells were co-cultured with ovarian cancer cells to format TAMs.

Results: Ovarian cancer tissues and cells exhibited upregulated KIF20A and downregulated PTEN levels (p < 0.05). Irradiation significantly decreased KIF20A levels (p < 0.05) and blunted the progression of ovarian cancer by reducing cell proliferation and EMT (p < 0.05) and inducing apoptosis (p < 0.05). These effects were augmented by KIF20A depletion (p < 0.05). KIF20A depletion also suppressed ovarian cancer cell progression (p < 0.05). Our findings illustrated that KIF20A negatively regulated PTEN expression in ovarian cancer cells. Moreover, the inhibitory effects of KIF20A depletion on ovarian cancer development in irradiated ovarian cancer cells were obviously impeded by PTEN knockdown (p < 0.05). Additionally, we observed the increased KIF20A expression in M2-like TAMs and its ability to induce M2 macrophage polarization (p < 0.05).

Conclusion: KIF20A was found to induce M2 macrophage polarization in ovarian cancer, and KIF20A depletion regulated PTEN to increase radiosensitivity and inhibit ovarian cancer development.

Background: To explore the mechanism of hyperbaric oxygen (HBO) intervention on acute lung injury secondary to Deinagkistrodon acutus snake venom poisoning and provide more toxicological and clinical evidence for Deinagkistrodon acutus venom poisoning.

Methods: Male Kunming mice (n = 96) were randomly divided into four groups: the control group which was not given any interventional treatments, venom group in which each mouse was injected with Deinagkistrodon acutus venom (1 mg/kg) through the tail vein, antivenom group in which each mouse was injected with anti-Deinagkistrodon acutus venom immediately after the model was successfully established, and HBO+antivenom group in which each mouse was given HBO treatment at 1 h, 5 h, 11 h and 23 h following the injection of antivenom. Lung tissues of mice were obtained and processed for the detection of the lung coefficient, the levels of inflammatory factors such as interleukin (IL)-6, IL-10 and IL-17, and the protein expression of retinoic acid receptor (RAR)-related orphan receptor gamma (RORγt) and forkhead box P3 (FOXP3). Separate lung tissue specimens were acquired for hematoxylin-eosin staining.

Results: Compared with the venom group, HBO+antivenom group exhibited (1) improved survival rate within 24 h; (2) resolution of pulmonary edema, integrity restoration of alveolar structure, and reduced number of infiltrated inflammatory cells; (3) diminished levels of pro-inflammatory factors and increased abundance of anti-inflammatory factors beginning 2 h after envenomation; and (4) balanced expression of RORγt protein and FOXP3 protein at 24 h after envenomation.

Conclusion: HBO combined with antivenom can significantly relieve secondary lung injury in mice poisoned with Deinagkistrodon acutus venom by immediately regulating the balance of helper T cell 17 (Th17)/regulatory T cell (Treg) related proteins.

Background: Lung cancer treatment remains a global challenge due to tumor cell resistance. Propofol, traditionally used as an anesthetic, has demonstrated potential anti-tumor properties. This study seeks to elucidate how propofol induces cell death in lung cancer cells by upregulating Pannexin 1 (PANX1) expression, activating the mitochondrial cell death pathway, and augmenting reactive oxygen species (ROS) production.

Methods: In this study, the A549 lung cancer cell line was employed as the experimental model. Cells underwent exposure to varying propofol concentrations and were pre-treated with H₂O₂ and N-acetylcysteine (NAC) to simulate oxidative stress and antioxidant conditions. Various techniques, including 5-Ethynyl-2'-deoxyuridine (EdU), colony formation, Transwell, 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA), Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL), and JC-1 (5,5',6,6'-Tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide) probes, were employed to evaluate propofol's effects on lung cancer cell viability, growth, invasion, ROS levels, apoptosis, and mitochondrial membrane potential. Western blot analysis was used to measure PANX1, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, and Cytochrome C (Cyt C) protein levels. Additionally, PANX1's influence on propofol-induced apoptosis was investigated through siRNA interference.

Results: The experiment unveiled propofol's dose-dependent inhibition of A549 lung cancer cell growth, coupled with decreased cell proliferation and invasion attributable to heightened ROS production. Notably, propofol treatment significantly elevated mitochondrial membrane potential, signifying activation of the mitochondrial cell death pathway (p < 0.01). Furthermore, propofol upregulated PANX1 expression (p < 0.01), thereby intensifying apoptosis signaling, whereas PANX1 inhibition ameliorated propofol-induced apoptosis (p < 0.01). These findings underscore the pivotal role of PANX1 upregulation and ROS augmentation in propofol-induced apoptosis in lung cancer cells.

Conclusion: This study provides evidence that propofol induces cell death in lung cancer cells by upregulating PANX1, activating the mitochondrial apoptosis pathway, and increasing ROS production. These findings suggest that targeting PANX1 and ROS could enhance the anti-cancer efficacy of propofol in lung cancer.

Utilizing metal complexes to inhibit histone deacetylases (HDACs) and carbonic anhydrases (CAs) highlights their therapeutic potential, particularly in anticancer strategies. The metal complexes, with their unique three-dimensional structures, fit adequately into the active sites of the enzymes, not only improving selectivity but also providing facile coordination with amino acid residues to enhance their inhibitory ability. This review emphasizes the role of metal complexes in the selective inhibition of HDACs and CAs along with details of their mechanism of action. Additionally, we summarize the inhibition ability and cytotoxicity of metal complexes targeting HDACs and CAs, as well as the therapeutic implications that can lead to the invention and development of metal complexes as potent anticancer agents.

Background: The incidence of atherosclerotic cardiovascular disease (ASCVD) is increasing, with individuals experiencing acute myocardial infarction (AMI) at a younger age. Premature AMI is a serious condition with high rates of morbidity and mortality. This study aimed to identify clinical characteristics and risk factors associated with premature AMI and to evaluate the diagnostic value of those risk factors.

Methods: The study collected data from first-time AMI patients who underwent coronary angiography at the hospital between January 2022 and April 2023. They were divided into two groups by age: premature AMI (men <55 years, women <65 years) and non-premature AMI. A control group of similar-aged patients without coronary artery disease was also included.

Results: Out of 388 patients with first-time AMI, 313 were male, and 249 had ST-segment elevation myocardial infarction (STEMI). Among 73 control patients, 31 were male. Those with premature AMI had more risk factors like smoking, overweight, obesity, family history of coronary artery disease, and STEMI. They also had shorter hospital stays and higher diastolic blood pressure and faster heart rates. Single-vessel lesions were more frequent in premature AMI patients. After adjusting for confounding factors, smoking status (Odds ratio (OR) 4.454, 95% confidence interval (CI): 1.836-10.806, p = 0.001), glycated hemoglobin (HbA1c) level (OR 2.261, 95% CI: 1.219-4.193, p = 0.010), the non-high-density lipoprotein cholesterol (non-HDL-C)/HDL-C ratio (OR 4.394, 95% CI: 1.204-16.031, p = 0.025), and the monocyte-to-high-density lipoprotein ratio (MHR) (OR 6.164, 95% CI: 1.386-27.417, p = 0.017) were identified as independent risk factors for premature AMI development. The combination of these risk factors provided the greatest predictive value for premature AMI (area under the curve (AUC) = 0.874, 95% CI: 0.826-0.922, p < 0.001, sensitivity = 0.843, specificity = 0.795).

Conclusions: Premature AMI is often characterized by STEMI, single-vessel lesions, and a low occurrence of left main coronary artery involvement. Smoking status, HbA1c levels, the non-HDL-C/HDL-C ratio, and the MHR are significantly associated with premature AMI.

Background: Our previous research revealed that daphnetin (7,8-dihydroxycou-marin) positively influences the balance between forked transcription factor P3 (Foxp3+) regulatory T cells (Treg) and T helper 17 (Th17) cells in the peripheral blood mononuclear cells of individuals with unexplained recurrent pregnancy loss. However, the specific mechanism remains unclear. This research aims to further examine how daphnetin regulates the Th17 cell/Foxp3+ Treg cell imbalance in a mouse model with unexplained recurrent spontaneous abortion (URSA).

Methods: Mice (n = 40) were allocated into the following groups: daphnetin high dose (4 mg/kg·day), daphnetin low dose (1 mg/kg·day), URSA model, and normal pregnancy (control). We used flow cytometry for assessing the Th17/Treg cell ratio in peripheral blood mononuclear cells, quantitative real-time polymerase chain reaction for measuring cytokine expression levels, and transmission electron microscopy for observing ultrastructural changes in decidual tissues and calculating the embryo absorption rate.

Results: Compared to the URSA model group, daphnetin significantly reduced the T17cell/Foxp3+ Treg cell ratio in peripheral blood mononuclear cells. Daphnetin also decreased the expression of Th17 cell-related cytokines, including orphan nuclear receptor γt (RORγt) and signal transduction and transcriptional activator 3 (STAT3), as well as increase the expression of Foxp3+ Treg cells-related cytokines, including STAT5 and Foxp3+. Furthermore, daphnetin reduced the embryo absorption rate and improved the decidual tissue ultrastructure of URSA model mice.

Conclusion: Daphnetin improves the Th17 cell/Foxp3+ Treg cell imbalance in URSA model mice, thereby contributing to the repair of decidual tissue damage and reducing the embryo absorption rate. These findings suggest that daphnetin may offer a new method for treating URSA.