Astaxanthin activates the Nrf2/Keap1/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity.

Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe2+ content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe2+ metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.

Real-Time Camera Image-Guided Nasoenteric Tube Placement in Prone COVID-19 ICU Patients: A Single-Center Study.

Background & Aims: This study aims to assess the application value of the real-time camera image-guided nasoenteric tube placement in critically ill COVID-19 patients undergoing endotracheal intubation and prone position ventilation therapy. Methods: We enrolled 116 COVID-19 patients receiving endotracheal intubation and prone position ventilation therapy in the intensive care unit (ICU). Patients were randomly divided into the real-time camera image-guided nasoenteric tube placement (n = 58) and bedside blind insertion (n = 58) groups. The success rate, placement time, complications, cost, heart rate, respiratory rate, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores were compared between the 2 groups. Results: For ICU patients with COVID-19 undergoing prone position ventilation therapy, the success rate and cost were significantly higher in the real-time camera image-guided group compared to the bedside blind group (P < .05). The placement time and complication incidence were significantly lower in the real-time camera image-guided group (P < .05). The differences in heart rate, respiratory rate, GCS scores, and APACHE-II scores were insignificant (P > .05). Conclusions: The real-time camera image-guided nasoenteric tube placement system had advantages for ICU COVID-19 patients undergoing prone position ventilation therapy, including a high success rate, short placement time, and no impact on patient position during tube placement. Real-time camera image-guided nasoenteric tube placement can be performed in any position, and demonstrates high efficiency, safety, and accuracy.

A multifaceted comparative analysis of image and video technologies in gastrointestinal endoscope and their clinical applications.

This paper presents a comprehensive exploration of endoscopic technologies in clinical applications across seven tables, each focusing on a unique facet of the medical field. The discourse begins with a detailed analysis of pediatric endoscopes, highlighting their diagnostic capabilities in various conditions. It then delves into the specifications and applications of globally recognized capsule endoscopy devices. Additionally, the paper incorporates an analysis of advanced imaging techniques, such as Narrow Band Imaging (NBI), Flexible Spectral Imaging Color Enhancement (FICE), and i-scan, which are increasingly being integrated into ultrathin gastrointestinal (GI) endoscopes. Factors like technological capabilities, light source, camera technology, and computational constraints are evaluated to understand their compatibility with these advanced imaging techniques, each offering unique advantages and challenges in clinical settings. NBI, for instance, is lauded for its user-friendly, real-time enhanced imaging capabilities, making it effective for early detection of conditions like colorectal cancer and Barrett's esophagus. Conversely, FICE and i-scan offer high customizability and are compatible with a broader range of endoscope models. The paper further delves into innovative advances in movement control for Nasojejunal (NJ) feeding tube endoscopy, elucidating the potential of AI and other novel strategies. A review of the technologies and methodologies enhancing endoscopic procedure control and diagnostic precision follows, emphasizing image and video technologies in pediatric endoscopy, capsule endoscopes, ultrathin endoscopes, and their clinical applications. Finally, a comparative analysis of leading real-time video monitoring endoscopes in clinical practices underscores the continuous advancements in the field of endoscopy, ensuring improved diagnostics and precision in surgical procedures. Collectively, the comparative analysis presented in this paper highlights the remarkable diversity and continuous evolution of endoscopic technologies, underlining their crucial role in diagnosing and treating an array of medical conditions, thereby fostering advancements in patient care and clinical outcomes.

Transgenerational effects of BDE-47 to zebrafish based on histomorphometry and toxicogenomic analyses.

Exposure to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) has been found to have an impact on reproductive output and endocrine function in female zebrafish (Danio rerio). However, the transgenerational effects of BDE-47 have not been fully explored in previous reports. In this study, female zebrafish were exposed to BDE-47 for three consecutive weeks. The oogenesis, sex hormones, reproductive histology, and transcriptional profiles of genes along the hypothalamus-pituitary-gonad (HPG) axis were assessed in the exposed-F0 generation. After mating with unexposed males, the transgenerational effects of BDE-47 were evaluated on the basis of histopathology, morphometry and toxicogenome of the unexposed F1 generations at the larval stage. Results indicated that exposure to BDE-47 impaired reproductive capacity, disrupted endocrine system in F0 zebrafish, and compromised craniofacial skeletons and vertebrae development in F1 generations. In addition, through the use of toxicogenomics approach, immune-responsive pathways were found to be significantly enriched, and the transcript expression profiling of immune-related DEGs (IRDs) were dramatically inhibited in F1 generations following maternal BDE-47 exposure, indicating its immunotoxicity to offspring larvae. These findings advance our understanding of the transgenerational toxicity of BDE-47 and advocate for a more comprehensive assessment of other PBDE congeners through histomorphometry and toxicogenomic approaches.

Comparative pharyngeal cartilage developmental toxicity of bisphenol A, bisphenol S and bisphenol AF to zebrafish (Danio rerio) larvae: A combination of morphometry and global transcriptome analyses.

Exposure to BPA is recently shown to affect cartilage development in teleost fishes; whether BPS and BPAF, its two most frequently used phenolic analogues have similar effect, however, remains unclear. Here, we utilize zebrafish (Danio rerio) as an in-vivo larval model for systematic comparison of the pharyngeal arch-derived cartilage developmental toxicity of BPA, BPS and BPAF. Zebrafish are continuously exposed to three bisphenol analogues (3-BPs) at a range of concentrations since the embryonic stage (0.5 hpf), and identified cartilage malformations of the mandibular and hyoid pharyngeal arches at larval stage (120 hpf). BPA and BPAF prolong length and broaden cartilage angles; however, BPS shortens length and narrows the angles of skull cartilages. The results of the comparative transcriptome show that FoxO and MAPK signaling pathways are closely associated with the toxicity of BPA and BPAF, while BPS exposure affects energy metabolism-related pathways. Moreover, exposure to 3-BPs have an impact on the oxidative stress status. Our data collectively indicate that BPS and BPAF may not be safer than BPA regarding the impact on pharyngeal cartilage development in fish model, the mechanisms still need explorations, and that these two analogues should be applied with caution.

Application of visual placement of a nasojejunal indwelling feeding tube in intensive care unit patients receiving mechanical ventilation.

Background: Compared with nasogastric nutrition, nasojejunal nutrition may prevent some complications of critically ill patients by maintaining better nutritional status, and blind placement of nasojejunal dwelling feeding tubes is widely used. However, the visual placement seems to be safer and more effective than the blind placement, and is still seldom reported. Objective: We tried to develop visual placement of a nasojejunal feeding tube in intensive care unit patients. Methods: A total of 122 patients receiving mechanical ventilation were admitted to the Department of Critical Care Medicine of the Fifth Affiliated Hospital of Wenzhou Medical University and received the placement of nasojejunal feeding tubes. These patients were randomly and evenly assigned into two groups, one group receiving visual placement of nasojejunal dwelling feeding tubes and another group receiving blind placement. Actual tube placement was confirmed by X-ray. The primary outcome included the success rates of first placement of feeding tubes. The secondary outcome included the time of tube placement, complications, the total cost, heart rates and respiratory rates. Results: The primary outcome showed that the success rates of first placement were 96.70% (59 cases/61 cases) in the visual placement group, and two cases failed due to pyloric stenosis and gastroparesis. The success rates were 83.6% (51 cases/61 cases) in the blind placement group and 10 cases failed due to either wrong placement or retrograde tube migration. The success rates in the visual placement group were higher than that in the blind placement group (P = 0.015). The secondary outcome showed that the time of tube placement in the visual placement group was shorter than that in the blind placement group (P < 0.0001). The cost of tube placement in the visual placement group was higher than that in the blind placement group (P < 0.0001). The statistical differences in complications, heart and respiratory rates were insignificant between the two groups (P > 0.05). Conclusion: Compared with the blind placement, the visual placement shortened the time of nasojejunal tube placement and increased success rates of first placement. The visual placement was more efficient, easy to operate, safe, and has potential clinical applications.

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis.

Glioma is the most common type of central nervous system tumor with increasing incidence. 7-methylguanosine (m7G) is one of the diverse RNA modifications that is known to regulate RNA metabolism and its dysregulation was associated with various cancers. However, the expression pattern of m7G regulators and their roles in regulating tumor immune microenvironments (TIMEs) as well as alternative splicing events (ASEs) in glioma has not been reported. In this study, we showed that m7G regulators displayed a close correlation with each other and most of them were differentially expressed between normal and glioma tissues. Two m7G signatures were then constructed to predict the overall survival of both GBM and LGG patients with moderate predictive performance. The risk score calculated from the regression coefficient and expression level of signature genes was proved to be an independent prognostic factor for patients with LGG, thus, a nomogram was established on the risk score and other independent clinical parameters to predict the survival probability of LGG patients. We also investigated the correlation of m7G signatures with TIMEs in terms of immune scores, expression levels of HLA and immune checkpoint genes, immune cell composition, and immune-related functions. While exploring the correlation between signature genes and the ASEs in glioma, we found that EIF4E1B was a key regulator and might play dual roles depending on glioma grade. By incorporating spatial transcriptomic data, we found a cluster of cells featured by high expression of PTN exhibited the highest m7G score and may communicate with adjacent cancer cells via SPP1 and PTN signaling pathways. In conclusion, our work brought novel insights into the roles of m7G modification in TIMEs and ASEs in glioma, suggesting that evaluation of m7G in glioma could predict prognosis. Moreover, our data suggested that blocking SPP1 and PTN pathways might be a strategy for combating glioma.

Intelligent Algorithm-Based Magnetic Resonance for Evaluating the Effect of Platelet-Rich Plasma in the Treatment of Intractable Pain of Knee Arthritis.

The application of intelligent algorithms in the treatment of intractable pain of patients with platelet-rich plasma (PRP) knee osteoarthritis by magnetic resonance was investigated. The automatic diagnosis of magnetic resonance knee osteoarthritis was established with multiple intelligent algorithms, including gray projection algorithm, adaptive binarization algorithm, and active shape model (ASM). The difference between automatic magnetic resonance detection indexes of the patients with knee osteoarthritis and artificial measurement results was analyzed. The included patients received PRP treatment. Knee osteoarthritis MRI osteoarthritis knee scores (KOA MOAKS) and Western Ontario and McMaster Universities arthritis index (WOMAC) before and after treatment were compared. The results showed that the results of knee osteoarthritis scores, inferior angle of femur, superior angle of tibia, and tibiofemoral angle (TFA) by automatic magnetic resonance diagnostic model were entirely consistent with artificial detection results. After the treatment, the total scores of knee lateral area, interior area, central area, and patellar area were all remarkably lower than those before the treatment (P < 0.05). After the treatment, knee KOA MOAKS scores and WOMAC scores were both lower than those before the treatment (P < 0.05). Visual analogue scale (VAS) scores 1 week, 2 weeks, and 3 weeks after the treatment were decreased compared with those before the treatment (P < 0.05). Relevant studies indicated that intelligent algorithm-based automatic magnetic resonance diagnostic knee osteoarthritis model showed good utilization values, which could provide the reference and basis for the treatment of the patients with knee osteoarthritis.

Corrigendum: Application of visual placement of a nasojejunal indwelling feeding tube in intensive care unit patients receiving mechanical ventilation.

[This corrects the article DOI: 10.3389/fmed.2022.1022815.].

Downregulation of lncRNA ZFAS1 and upregulation of microRNA-129 repress endocrine disturbance, increase proliferation and inhibit apoptosis of ovarian granulosa cells in polycystic ovarian syndrome by downregulating HMGB1.

OBJECTIVE: The objective was to find the role of long-non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1)/microRNA (miR)-129/high-mobility group box protein 1 (HMGB1) axis in polycystic ovary syndrome (PCOS). METHODS: Ovarian granulosa cells from non-PCOS patients and PCOS patients were collected, and HMGB1, miR-129 and lncRNA ZFAS1 expression were detected. Ovarian granulosa cells were transfected with si-ZFAS1 or miR-129 mimics to verify their roles in P4 and E2 secretion, and the biological functions of ovarian granulosa cells. RESULTS: LncRNA ZFAS1 and HMGB1 were elevated, while miR-129 was down-regulated in ovarian granulosa cells of PCOS patients. Down-regulated lncRNA ZFAS1 or overexpressed miR-129 could decrease HMGB1 expression, increase P4 and E2 secretion, promote proliferation activity while inhibit apoptosis of ovarian granulosa cells in PCOS. CONCLUSION: LncRNA ZFAS1 could bind to miR-129 to promote HMGB1 expression, thereby affecting the endocrine disturbance, proliferation and apoptosis of ovarian granulosa cells in PCOS.

Bu Shen Yang Xue Prescription Has Treating Effect on Endometrial Cancer through FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD 1 Pathway in Ishikawa Cells.

Background. The formulation of Bu Shen Yang Xue (BSYX) has been clinically used in treating gynecologic disease in China, especially for the development of the endometrium. Endometrial carcinoma is the most common malignant tumor of the female genital tract in developed countries. And few studies have been reported on the antitumor activity of BSYX. Therefore, this study aimed to investigate the effect of BSYX on endometrial cancer and make an initial discussion of the underlining mechanisms in Ishikawa cells. Methods and Results. Firstly, 60 SPF female nude mice were randomly divided into control group, model group, BSYX group, and positive group. The models of subcutaneous tumor xenograft of nude mice were established by injection of human endometrial carcinoma cell line Ishikawa tumor cell suspension. Compared with model group, BSYX reduced effectively tumor volume and changed pathological feature in mice tumor issue. Meanwhile, proteins from tumor issues were detected by western blot analysis. The protein levels of follicle-stimulating hormone receptor (FSHR), p-Akt/Akt, Gankyrin, and cyclinD1 in the model group were higher than those in control group but the expression in BSYX group was lower than that in the model group. The hypoxia inducible factor alpha (HIF-α) protein level in the model group was lower than those in control group and upregulated in BSYX group. In addition, Ishikawa cells were cultured and then exposed to follicle-stimulating hormone (FSH), LY294002, a highly selective PI3K inhibitor and serum containing BSYX, respectively. LY294002 and BSYX markedly decreased the cancer cell viability and migration ability and increased the apoptosis rate. FSH promoted the cancer cell ability and migration ability. LY294002 and BSYX evidently downregulated the proteins levels of FSHR, p-Akt/Akt, Gankyrin, and cyclinD1 and upregulated the expression of HIF-α protein, and FSH was on the opposite. Conclusions. Taken together, our results showed that the formulation of BSYX had antitumor effect on endometrial cancer in vivo and in vitro and was related with FSH/PI3K/AKT/Gankyrin/HIF-α/cyclinD1 transduction pathway.