Molecular hydrogen promotes retinal vascular regeneration and attenuates neovascularization and neuroglial dysfunction in oxygen-induced retinopathy mice.

BACKGROUND: Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. METHODS: In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. RESULTS: Our results indicate that 3-4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. CONCLUSIONS: Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.

circCUL3 drives malignant progression of cervical cancer by activating autophagy through sponge miR-223-3p upregulation of ATG7.

Circular RNA (circRNA) has emerged as a pivotal regulatory factor in cancer biology, yet its exact role in cervical cancer remains incompletely understood. In this study, we investigated the functional role of circCUL3 in cervical cancer and explored its potential as a therapeutic target. Functional gain and loss experiments were conducted in Hela and Siha cell lines to elucidate the biological functions of circCUL3 in cervical cancer. The results revealed that circCUL3 overexpression significantly enhanced cell viability, migration, and invasion while suppressing apoptosis, while circCUL3 knockout displayed the opposite effects. Mechanistically, we identified hsa-miR-223-3p as a target of circCUL3, with its expression being negatively regulated by circCUL3. Furthermore, we discovered that circCUL3 could sequester miR-223-3p, leading to the upregulation of ATG7 expression, and this was linked to the regulation of autophagy in cervical cancer cells. In vivo validation using a xenograft mouse model further supported our in vitro findings. Notably, we found that chloroquine (CQ), an autophagy inhibitor, restored miR-223-3p expression and counteracted the oncogenic effect of circCUL3 overexpression. In conclusion, circCUL3 potentially contributes to the malignant progression of cervical cancer by acting as a sponge for miR-223-3p, resulting in the upregulation of ATG7 and the activation of autophagy.

Effect of increased pCO2 and temperature on the phytoplankton community in the coastal of Yellow Sea.

In order to study the dynamics of marine phytoplankton communities in response to anticipated in temperature and CO2, a shipboard continuous culture experiment (Ecostat) was conducted. The experiment involved simulations under current atmospheric CO2 concentrations (400 ppm) and projected year-2100 CO2 levels (1000 ppm), as well as varying temperature under present (22 °C) versus increased temperature (26 °C) in the Yellow Sea during the summer of 2020. The results showed that both the increased pCO2 and temperature had significant effects on microphytoplankton and picophytoplankton, with the warming effect proving to be more significant. The different responses of various species to acidification and warming and their coupling effect led to the changes in microphytoplankton and picophytoplankton community structure. Elevated temperature and greenhouse treatments promoted the growth of dominant diatoms and Synechococcus, such as Guinardia flaccida and Pseudo-nitzschia delicatissima. This phenomenons widened the ecological niche, and the changes in the growth patterns of dominant species consequently influenced the content of cellular elements. Mantel's analysis further demonstrated that both warming and greenhouse promoted the growth of diatoms and Synechococcus. Projections of marine phytoplankton community trends by the end of the century based on Growth Rate Ratio (GRR), indicated that not only would species with GRR < 1 decrease, but also numerous species with growth rates >1 at elevated pCO2 levels would be ousted from competition. This experiment demonstrates the need to investigate whether extended exposure to increased pCO2 and temperature over more extended time scales would similarly induce shifts in the biological and biogeochemical dynamics of the Yellow Sea.

Ferroptosis in cardiovascular disease.

In the 21st century, cardiovascular disease (CVD) has become one of the leading causes of death worldwide. The prevention and treatment of CVD remain pressing scientific issues. Several recent studies have suggested that ferroptosis may play a key role in CVD. Most studies conducted thus far on ferroptosis and CVD have supported the link. Ferroptosis mediated by different signaling and metabolic pathways can lead to ischemic heart disease, myocarditis, heart failure, ischemia-reperfusion injury, and cardiomyopathy. Still, the specific mechanism of ferroptosis in CVD, the particular organ areas affected, and the stage of disease involved need to be further studied. Therefore, understanding the mechanisms regulating ferroptosis in CVD may improve disease management. Throughout this review, we summarized the mechanism of ferroptosis and its effect on the pathogenesis of CVD. We also predicted and discussed future research directions, aiming to provide new ideas and strategies for preventing and treating CVD.

Nomogram for predicting severe abdominal pain after initial conventional transarterial chemoembolisation for hepatocellular carcinoma: a retrospective study.

Transarterial chemoembolisation (TACE) is a standard therapy for hepatocellular carcinoma (HCC). However, adverse events, including abdominal pain, are common. This study aimed to investigate and verify the feasibility of a nomogram model to predict severe abdominal pain after first conventional TACE (cTACE) among patients with HCC. Patients with HCC treated with cTACE between October 28, 2019, and August 5, 2022, at a single centre were enrolled (n = 216). Patients were divided into training and validation cohorts (ratio, 7:3). A visual analogue scale score between 7 and 10 was considered severe abdominal pain. A total of 127 (58.8%) patients complained of severe abdominal pain after first cTACE treatment. The nomogram considered age and tumour number and size. The nomogram demonstrated good discrimination, with a C-index of 0.749 (95% confidence interval [CI], 0.617, 0.881). Further, the C-index in the validation cohort reached 0.728 (95% CI 0.592, 0.864). The calibration curves showed ideal agreement between the prediction and real observations, and the nomogram decision curve analysis performed well. The nomogram model can provide an accurate prediction of severe abdominal pain in patients with HCC after first cTACE, aiding in the personalization of pain management and providing novel insights into hospital nursing.

Proteomic analysis to identification of hypoxia related markers in spinal tuberculosis: a study based on weighted gene co-expression network analysis and machine learning.

OBJECTIVE: This article aims at exploring the role of hypoxia-related genes and immune cells in spinal tuberculosis and tuberculosis involving other organs. METHODS: In this study, label-free quantitative proteomics analysis was performed on the intervertebral discs (fibrous cartilaginous tissues) obtained from five spinal tuberculosis (TB) patients. Key proteins associated with hypoxia were identified using molecular complex detection (MCODE), weighted gene co-expression network analysis(WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature Elimination (SVM-REF) methods, and their diagnostic and predictive values were assessed. Immune cell correlation analysis was then performed using the Single Sample Gene Set Enrichment Analysis (ssGSEA) method. In addition, a pharmaco-transcriptomic analysis was also performed to identify targets for treatment. RESULTS: The three genes, namely proteasome 20 S subunit beta 9 (PSMB9), signal transducer and activator of transcription 1 (STAT1), and transporter 1 (TAP1), were identified in the present study. The expression of these genes was found to be particularly high in patients with spinal TB and other extrapulmonary TB, as well as in TB and multidrug-resistant TB (p-value < 0.05). They revealed high diagnostic and predictive values and were closely related to the expression of multiple immune cells (p-value < 0.05). It was inferred that the expression of PSMB9, STAT 1, and TAP1 could be regulated by different medicinal chemicals. CONCLUSION: PSMB9, STAT1, and TAP1, might play a key role in the pathogenesis of TB, including spinal TB, and the protein product of the genes can be served as diagnostic markers and potential therapeutic target for TB.

Analysis of complete mitochondrial genome sequence of Kessleri thrush, Turdus kessleri (Passeriformes, Turdidae).

In this study, the complete mitochondrial genome of T. kessleri was sequenced and characterized. The overall base composition of T. kessleri mitogenome is 29.3% for A, 32.3% for C, 15.0% for G, and 23.5% for T. The percentage of G + C content is 47.2%. The mitogenome is a circular DNA molecule of 16,754 bp in length, including a D-loop region, two rRNA genes (12SrRNA and 16SrRNA), 13 protein-coding genes (PCGs), and 22 tRNA genes. The sequence information of T. kessleri can contribute to enrich the molecular data resources about birds and could also enable the phylogenetic research and help to resolve phylogenetic relationship problems related to Turdus.