Itaconate protects ferroptotic neurons by alkylating GPx4 post stroke.

Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.

The endonuclease FEN1 mediates activation of STAT3 and facilitates proliferation and metastasis in breast cancer.

BACKGROUND: The metastasis accounts for most deaths from breast cancer (BRCA). Understanding the molecular mechanisms of BRCA metastasis is urgently demanded. Flap Endonuclease 1 (FEN1), a pivotal factor in DNA metabolic pathways, contributes to tumor growth and drug resistance, however, little is known about the role of FEN1 in BRCA metastasis. METHODS AND RESULTS: In this study, FEN1 expression and its clinical correlation in BRCA were investigated using bioinformatics, showing being upregulated in BRCA samples and significant relationships with tumor stage, node metastasis, and prognosis. Immunohistochemistry (IHC) staining of local BRCA cohort indicated that the ratio of high FEN1 expression in metastatic BRCA tissues rose over that in non-metastatic tissues. The assays of loss-of-function and gain-of-function showed that FEN1 enhanced BRCA cell proliferation, migration, invasion, xenograft growth as well as lung metastasis. It was further found that FEN1 promoted the aggressive behaviors of BRCA cells via Signal Transducer and Activator of Transcription 3 (STAT3) activation. Specifically, the STAT3 inhibitor Stattic thwarted the FEN1-induced enhancement of migration and invasion, while the activator IL-6 rescued the decreased migration and invasion caused by FEN1 knockdown. Additionally, overexpression of FEN1 rescued the inhibitory effect of nuclear factor-κB (NF-κB) inhibitor BAY117082 on phosphorylated STAT3. Simultaneously, the knockdown of FEN1 attenuated the phosphorylation of STAT3 promoted by the NF-κB activator tumor necrosis factor α (TNF-α). CONCLUSIONS: These results indicate a novel mechanism that NF-κB-driven FEN1 contributes to promoting BRCA growth and metastasis by STAT3 activation.

Ultra-sensitive analysis of exhaled biomarkers in ozone-exposed mice via PAI-TOFMS assisted with machine learning algorithms.

Ground-level ozone ranks sixth among common air pollutants. It worsens lung diseases like asthma, emphysema, and chronic bronchitis. Despite recent attention from researchers, the link between exhaled breath and ozone-induced injury remains poorly understood. This study aimed to identify novel exhaled biomarkers in ozone-exposed mice using ultra-sensitive photoinduced associative ionization time-of-flight mass spectrometry and machine learning. Distinct ion peaks for acetonitrile (m/z 42, 60, and 78), butyronitrile (m/z 70, 88, and 106), and hydrogen sulfide (m/z 35) were detected. Integration of tissue characteristics, oxidative stress-related mRNA expression, and exhaled breath condensate free-radical analysis enabled a comprehensive exploration of the relationship between ozone-induced biological responses and potential biomarkers. Under similar exposure levels, C57BL/6 mice exhibited pulmonary injury characterized by significant inflammation, oxidative stress, and cardiac damage. Notably, C57BL/6 mice showed free radical signals, indicating a distinct susceptibility profile. Immunodeficient non-obese diabetic Prkdc-/-/Il2rg-/- (NPI) mice exhibited minimal biological responses to pulmonary injury, with little impact on the heart. These findings suggest a divergence in ozone-induced damage pathways in the two mouse types, leading to alterations in exhaled biomarkers. Integrating biomarker discovery with comprehensive biopathological analysis forms a robust foundation for targeted interventions to manage health risks posed by ozone exposure.

Effect of PCI on ophthalmic artery hemodynamics in patients with acute coronary syndrome.

Purpose: We aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS). Methods: A total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters. Results: The angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators. Conclusions: The OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions. Trial registration: ChiCTR2100050428.

Investigating diagnostic potential of long non-coding RNAs in head and neck squamous cell carcinoma using TCGA database and clinical specimens.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent and prognostically challenging cancer worldwide. The role of long non-coding RNAs (lncRNAs) in cancer regulation is progressively being understood. This study aims to identify lncRNAs with diagnostic potential as biomarkers for HNSCC. Statistical analysis was performed on expression data from the Cancer Genome Atlas (TCGA) database to identify potential lncRNAs associated with HNSCC. Four selected lncRNAs were validated using real-time quantitative reverse transcription polymerase chain reaction and correlated with clinical factors. Functional roles were further investigated. A total of 488 differentially expressed lncRNAs were identified in TCGA-HNSC. After rigorous evaluation based on p-values, survival analysis, and ROC analysis, 24 lncRNAs were prioritized for additional investigation. LINC00460, LINC00941, CTC-241F20.4, and RP11-357H14.17 were established as candidate diagnostic biomarkers. These lncRNAs exhibited elevated expression in HNSCC tissues and were associated with poor prognosis. Combining them showed high diagnostic accuracy. Notably, LINC00460 and CTC-241F20.4 demonstrated a significant elevation in the advanced stages of HNSCC. We constructed an lncRNA-mRNA regulatory network, and the array of significant regulatory pathways identified included focal adhesion, regulation of epithelial cell migration, and others. Additionally, these lncRNAs were found to influence immune responses by modulating immune cell infiltration in the HNSCC microenvironment. Our research indicates that LINC00460, LINC00941, RP11-357H14.17, and CTC-241F20.4 may have diagnostic and prognostic importance in HNSCC. Furthermore, we have gained insights into their potential functional roles, particularly about immune responses and interactions in the microenvironment.

Targeted macrophage phagocytosis by Irg1/itaconate axis improves the prognosis of intracerebral hemorrhagic stroke and peritonitis.

BACKGROUND: Macrophages are innate immune cells whose phagocytosis function is critical to the prognosis of stroke and peritonitis. cis-aconitic decarboxylase immune-responsive gene 1 (Irg1) and its metabolic product itaconate inhibit bacterial infection, intracellular viral replication, and inflammation in macrophages. Here we explore whether itaconate regulates phagocytosis. METHODS: Phagocytosis of macrophages was investigated by time-lapse video recording, flow cytometry, and immunofluorescence staining in macrophage/microglia cultures isolated from mouse tissue. Unbiased RNA-sequencing and ChIP-sequencing assays were used to explore the underlying mechanisms. The effects of Irg1/itaconate axis on the prognosis of intracerebral hemorrhagic stroke (ICH) and peritonitis was observed in transgenic (Irg1flox/flox; Cx3cr1creERT/+, cKO) mice or control mice in vivo. FINDINGS: In a mouse model of ICH, depletion of Irg1 in macrophage/microglia decreased its phagocytosis of erythrocytes, thereby exacerbating outcomes (n = 10 animals/group, p < 0.05). Administration of sodium itaconate/4-octyl itaconate (4-OI) promoted macrophage phagocytosis (n = 7 animals/group, p < 0.05). In addition, in a mouse model of peritonitis, Irg1 deficiency in macrophages also inhibited phagocytosis of Staphylococcus aureus (n = 5 animals/group, p < 0.05) and aggravated outcomes (n = 9 animals/group, p < 0.05). Mechanistically, 4-OI alkylated cysteine 155 on the Kelch-like ECH-associated protein 1 (Keap1), consequent in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and transcriptional activation of Cd36 gene. Blocking the function of CD36 completely abolished the phagocytosis-promoting effects of Irg1/itaconate axis in vitro and in vivo. INTERPRETATION: Our findings provide a potential therapeutic target for phagocytosis-deficiency disorders, supporting further development towards clinical application for the benefit of stroke and peritonitis patients. FUNDING: The National Natural Science Foundation of China (32070735, 82371321 to Q. Li, 82271240 to F. Yang) and the Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education (KZ202010025033 to Q. Li).

Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.

AIM: Mitochondrial dysfunction, a characteristic pathological feature of renal Ischemic/reperfusion injury (I/RI), predisposes tubular epithelial cells to maintain an inflammatory microenvironment, however, the exact mechanisms through which mitochondrial dysfunction modulates the induction of tubular injury remains incompletely understood. METHODS: ESI-QTRAP-MS/MS approach was used to characterize the targeted metabolic profiling of kidney with I/RI. Tubule injury, mitochondrial dysfunction, and fumarate level were evaluated using qPCR, transmission electron microscopy, ELISA, and immunohistochemistry. RESULTS: We demonstrated that tubule injury occurred at the phase of reperfusion in murine model of I/RI. Meanwhile, enhanced glycolysis and mitochondrial dysfunction were found to be associated with tubule injury. Further, we found that tubular fumarate, which resulted from fumarate hydratase deficiency and released from dysfunctional mitochondria, promoted tubular injury. Mechanistically, fumarate induced tubular injury by causing disturbance of glutathione (GSH) hemostasis. Suppression of GSH with buthionine sulphoximine administration could deteriorate the fumarate inhibition-mediated tubule injury recovery. Reactive oxygen species/NF-κB signaling activation played a vital role in fumarate-mediated tubule injury. CONCLUSION: Our studies demonstrated that the mitochondrial-derived fumarate promotes tubular epithelial cell injury in renal I/RI. Blockade of fumarate-mediated ROS/NF-κB signaling activation may serve as a novel therapeutic approach to ameliorate hypoxic tubule injury.

Alterations in the diversity, composition and function of the gut microbiota in Uyghur individuals with sarcopenia.

BACKGROUND: Research on the gut microbiota has emerged as a new direction for understanding pathophysiologic changes in diseases associated with aging, such as sarcopenia. Several studies have shown that there are differences in the gut microbiota between individuals with sarcopenia and without sarcopenia. However, these differences are not consistent across regions and ethnic groups, and additional research is needed. METHODS: In this study, we collected fresh fecal samples from 31 Uyghur individuals with sarcopenia and 31 healthy controls. We used 16S rRNA sequencing to obtain fecal base sequences and analyzed the diversity, composition and function of the gut microbiota. RESULTS: There was no significant difference in alpha diversity between the sarcopenia group and the healthy control group (P > 0.05). There was a significant difference in beta diversity between the groups (P < 0.05). In the sarcopenia group, the abundances of Alloprevotella, un_f_Prevotellaceae, Anaerovibrio, Prevotellaceae_NK3B31_group, Mitsuokella, Prevotella and Allisonella were lower than those in the heathy control group, and the abundances of Flavobacteriales, Flavobacteriaceae, Catenibacterium, Romboutsia, Erysipelotrichaceae_UCG-003, GCA-900066575, Lachnospiraceae_FCS020_group, and un_f_Flavobacteriaceae were higher than those in the heathy control group. Linear discriminant analysis effect size (LEfSe) revealed that the microbial species in the control group that were significantly different from those in the sarcopenia group were concentrated in the genus Alloprevotella, while the species in the sarcopenia group were concentrated in the genus Catenibacterium. Functional prediction analysis revealed that D-alanine, glycine, serine, and threonine metabolism and transcription machinery, among others, were enriched in the sarcopenia group, which indicated that metabolic pathways related to amino acid metabolism and nutrient transport may be regulated to varying degrees in the pathophysiological context of sarcopenia. CONCLUSIONS: There were significant differences in the composition and function of the gut microbiota between Xinjiang Uyghur sarcopenia individuals and healthy individuals. These findings might aid in the development of probiotics or microbial-based therapies for sarcopenia in Uyhur individuals.

DDAH1 recruits peroxiredoxin 1 and sulfiredoxin 1 to preserve its activity and regulate intracellular redox homeostasis.

Growing evidence suggests that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a crucial enzyme for the degradation of asymmetric dimethylarginine (ADMA), is closely related to oxidative stress during the development of multiple diseases. However, the underlying mechanism by which DDAH1 regulates the intracellular redox state remains unclear. In the present study, DDAH1 was shown to interact with peroxiredoxin 1 (PRDX1) and sulfiredoxin 1 (SRXN1), and these interactions could be enhanced by oxidative stress. In HepG2 cells, H2O2-induced downregulation of DDAH1 and accumulation of ADMA were attenuated by overexpression of PRDX1 or SRXN1 but exacerbated by knockdown of PRDX1 or SRXN1. On the other hand, DDAH1 also maintained the expression of PRDX1 and SRXN1 in H2O2-treated cells. Furthermore, global knockout of Ddah1 (Ddah1-/-) or liver-specific knockout of Ddah1 (Ddah1HKO) exacerbated, while overexpression of DDAH1 alleviated liver dysfunction, hepatic oxidative stress and downregulation of PRDX1 and SRXN1 in CCl4-treated mice. Overexpression of liver PRDX1 improved liver function, attenuated hepatic oxidative stress and DDAH1 downregulation, and diminished the differences between wild type and Ddah1-/- mice after CCl4 treatment. Collectively, our results suggest that the regulatory effect of DDAH1 on cellular redox homeostasis under stress conditions is due, at least in part, to the interaction with PRDX1 and SRXN1.

IL-8 activates fibroblasts to promote the invasion of HNSCC cells via STAT3-MMP1.

Matrix metalloproteinase-1 (MMP1) has an aberrant expression relevant to various behaviors of cancers. As dominant components of the tumor stroma, fibroblasts constitute an important source of Matrix metalloproteinase (MMPs) including mainly MMP1. The impacts of MMP1 derived from fibroblasts in tumor microenvironment, however, is not well defined. In this study, we demonstrated a part of crosstalk between fibroblasts and cancer cells that enhanced the invasiveness of cancer cells, IL8-induced activation of STAT3 signaling pathway as a key promoter to elevated MMP1 level in fibroblasts that supports the migration and invasion of head and neck squamous cell carcinoma (HNSCC) cells by extracellular matrix degradation. Importantly, once exposed to the inhibitor of STAT3 phosphorylation (TPCA-1), the enhanced induction of HNSCC cells invasion triggered by fibroblasts was significantly impaired.

Timing theory integrated nursing combined behavior change integrated theory of nursing on primiparous influence.

BACKGROUND: The comprehension and utilization of timing theory and behavior change can offer a more extensive and individualized provision of support and treatment alternatives for primipara. This has the potential to enhance the psychological well-being and overall quality of life for primipara, while also furnishing healthcare providers with efficacious interventions to tackle the psychological and physiological obstacles encountered during the stages of pregnancy and postpartum. AIM: To explore the effect of timing theory combined with behavior change on self-efficacy, negative emotions and quality of life in patients with primipara. METHODS: A total of 80 primipara cases were selected and admitted to our hospital between August 2020 and May 2022. These cases were divided into two groups, namely the observation group and the control group, with 40 cases in each group. The nursing interventions differed between the two groups, with the control group receiving routine nursing and the observation group receiving integrated nursing based on the timing theory and behavior change. The study aimed to compare the pre- and post-nursing scores of Chinese Perceived Stress Scale (CPSS), Edinburgh Postpartum Depression Scale (EPDS), Self-rating Anxiety Scale (SAS), breast milk knowledge, self-efficacy, and SF-36 quality of life in both groups. RESULTS: After nursing, the CPSS, EPDS, and SAS scores of the two groups was significantly lower than that before nursing, and the CPSS, EPDS, and SAS scores of the observation group was significantly lower than that of the control group (P = 0.002, P = 0.011, and P = 0.001 respectively). After nursing, the breastfeeding knowledge mastery, self-efficacy, and SF-36 quality of life scores was significantly higher than that before nursing, and the breastfeeding knowledge mastery (P = 0.013), self-efficacy (P = 0.008), and SF-36 quality of life (P = 0.011) scores of the observation group was significantly higher than that of the control group. CONCLUSION: The integration of timing theory and behavior change integrated theory has been found to be an effective approach in alleviating negative mood and stress experienced by primipara individuals, while also enhancing their self-efficacy and overall quality of life. This study focuses on the key concepts of timing theory, behavior change, primipara individuals, negative mood, and quality of life.

Association between dietary intake of saturated fatty acid subgroups and breast cancer risk.

The impact of dietary saturated fatty acids (SFAs) on breast cancer risk may vary depending on their carbon chain lengths, attributable to the discrepancy in their dietary sources and biological activities. The associations between SFA subgroups classified by chain length and breast cancer risk remain controversial. In this case-control study, we aimed to investigate the association between the dietary intake of SFA subgroups, classified by chain lengths, and odds of breast cancer in China. This study included 1661 cases of breast cancer (confirmed as primary and histologically) and 1674 frequency-matched controls. Face-to-face interviews were used to collect basic information, while dietary intake information was obtained by a food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). All SFA subgroups were inversely associated with odds of breast cancer. The adjusted ORs (95% CIs) were 0.78 (0.61-0.99) for medium-chain SFAs, 0.50 (0.31-0.83) for long even-chain SFAs, 0.69 (0.54-0.88) for long odd-chain, and 0.67 (0.48-0.95) for very long-chain SFAs, respectively. In the restricted cubic spline (RCS) models, a non-linear M-shaped association was observed between long odd-chain SFAs and odds of breast cancer (Pnon-linearity = 0.007). However, the associations of medium-chain SFAs, long even-chain SFAs, and very long-chain SFAs did not reach statistical significance (Pnon-linearity > 0.05). No significant interactions were observed between all these four subgroups of SFAs and menopausal status or BMI. Our findings emphasize the significance of elucidating the associations of dietary SFAs according to chain lengths, providing insights into the etiology as well as the potential benefits of SFA-rich food intake in reducing the risk of breast cancer. Further prospective cohort studies and intervention studies are warranted to confirm these findings and identify the underlying mechanisms of the association between dietary SFAs and breast cancer.

Accuracy comparison of scan segmental sequential ranges with two intraoral scanners for maxilla and mandible.

Background/purpose: The accuracy of a full-arch scan by using an intraoral scanner should be validated under clinical conditions. This study aimed to compare the accuracy of full-arch digital impressions in the maxilla and mandible using two intra oral scanners with three different scan segmental sequential ranges. Materials and methods: A dental model with 28 teeth in their normal positions served as the reference. Sixty full-arch scans were performed using Trios 3 and Trios 4, employing scanning strategy O (manufacturer's original method), OH (segmental sequential ranges one half), and TQ (segmental sequential ranges third quarter). Trueness was evaluated by comparing digital impressions with a reference dataset using specialized software. One-way ANOVA and Tukey tests assessed differences between the groups. Results: For Trios 3 on the maxilla, no significant difference was found among the groups of trueness; in the mandible, strategy O exhibited a significant difference (P = 0.008) with the highest deviation. For Trios 4 on the maxilla, strategy TQ demonstrated the lowest deviation with a significant difference (P = 0.006); in the mandible, no significant difference was found among the groups of trueness. Conclusion: Strategy TQ exhibited the best trueness for Trios 3 and Trios 4, suggesting it may be preferred for higher accuracy. Clinicians should consider these findings when selecting scanning strategies and intraoral scanners for specific cases.

Trueness of intraoral scanning for different tooth-size arch-length deficiencies.

Background/purpose: As science and technology continue to advance, the utilization of intraoral scanners (IOSs) has become increasingly popular in the orthodontic workflow. The aim of this study was to discuss whether the degree of crowded arches affects scan accuracy. Materials and methods: Three different crowding levels of dental models (model MI: mild, model MO: moderate, and model SE: severe) were scanned using both an IOS and desktop scanner. Stereolithographic files were obtained and superimposed via CAD software to calculate differences between each measuring point of a model and the farthest corresponding point. The deviations from three models were compared with statistical analysis. Results: The trueness of different crowding arches showed that the deviation value of model SE was the maximum, followed by model MI, and model MO in the maxillary arch. In the mandibular arch, the order of the deviation from greatest to least was firstly model SE, then model MO, and model MI. Significant differences were observed among the maxillary models (P < 0.001), but there was no significant difference between models in the mandible (P = 0.669). Conclusion: The trueness of the three crowded arches is in the clinically acceptable range. The degree of crowding increases, the trueness of scanning at each position decreases. In the maxillary arch, more severe crowding corresponds to higher deviations. In the mandible, the degree of crowding is not explicitly related to the maximum deviation; therefore, the clinician should notice the deviation when using IOSs for crowding cases.

Convolutional-neural-network-based radiographs evaluation assisting in early diagnosis of the periodontal bone loss via periapical radiograph.

Background/Purpose: The preciseness of detecting periodontal bone loss is examiners dependent, and this leads to low reliability. The need for automated assistance systems on dental radiographic images has been increased. To the best of our knowledge, no studies have quantitatively and automatically staged periodontitis using dental periapical radiographs. The purpose of this study was to evaluate periodontal bone loss and periodontitis stage on dental periapical radiographs using deep convolutional neural networks (CNNs). Materials and methods: 336 periapical radiographic images (teeth: 390) between January 2017 and December 2019 were collected and de-identified. All periapical radiographic image datasets were divided into training dataset (n = 82, teeth: 123) and test dataset (n = 336, teeth: 390). For creating an optimal deep CNN algorithm model, the training datasets were directly used for the segmentation and individual tooth detection. To evaluate the diagnostic power, we calculated the degree of alveolar bone loss deviation between our proposed method and ground truth, the Pearson correlation coefficients (PCC), and the diagnostic accuracy of the proposed method in the test datasets. Results: The periodontal bone loss degree deviation between our proposed method and the ground truth drawn by the three periodontists was 6.5 %. In addition, the overall PCC value of our proposed system and the periodontists' diagnoses was 0.828 (P < 0.01). The total diagnostic accuracy of our proposed method was 72.8 %. The diagnostic accuracy was highest for stage III (97.0 %). Conclusion: This tool helps with diagnosis and prevents omission, and this may be especially helpful for inexperienced younger doctors and doctors in underdeveloped countries. It could also dramatically reduce the workload of clinicians and timely access to periodontist care for people requiring advanced periodontal treatment.

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling.

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-ß-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

8-Br-cGMP suppresses tumor progression through EGFR/PLC γ1 pathway in epithelial ovarian cancer.

BACKGROUND: Cyclic guanosine monophosphate (cGMP)-dependent protein kinase I (PKG-I), a serine/threonine kinase, is important in tumor development. The present study determines that the cGMP/PKG I pathway is essential for promoting cell proliferation and survival in human ovarian cancer cells, whereas cGMP analog has been shown to lead to growth inhibition and apoptosis of various cancer cells. The role of cGMP/PKG I pathway in epithelial ovarian cancer (EOC), therefore, remains controversial. We investigated the effect of cGMP/PKG I pathway and the underlying mechanism in EOC. METHODS AND RESULTS: The results showed that exogenous 8-Bromoguanosine-3', 5'-cyclic monophosphate (8-Br-cGMP) (cGMP analog) could antagonize the effects by EGF, including suppressing proliferation, invasion and migration of EOC cells. In vivo, 8-Br-cGMP hampered the growth of the xenograft tumor. Additionally, the expressions of epidermal growth factor receptor (EGFR), matrix metallopeptidase 9 (MMP9), proliferating cell nuclear antigen and Ki67 in xenograft tumor were decreased after 8-Br-cGMP intervention. Further research demonstrated that 8-Br-cGMP decreased the phosphorylation of EGFR (Y992) and downstream proteins phospholipase Cγ1 (PLC γ1) (Y783), calmodulin kinase II (T286) and inhibited cytoplasmic Ca2+ release as well as PKC transferring to cell membrane. It's worth noting that the inhibition was 8-Br-cGMP dose-dependent and 8-Br-cGMP showed similar inhibitory effect on EOC cells compared with U-73122, a specific inhibitor of PLC γ1. CONCLUSIONS: The activation of endogenous PKG I by addition of exogenous 8-Br-cGMP could inhibit EOC development probably via EGFR/PLCγ1 signaling pathway. 8-Br-cGMP/PKG I provide a new insight and strategy for EOC treatment.

Clinical nursing value of predictive nursing in reducing complications of pregnant women undergoing short-term massive blood transfusion during cesarean section.

BACKGROUND: Cesarean hemorrhage is one of the serious complications, and short-term massive blood transfusion can easily cause postoperative infection and physical stress response. However, predictive nursing intervention has important clinical significance for it. AIM: To explore the effect of predictive nursing intervention on the stress response and complications of women undergoing short-term mass blood transfusion during cesarean section (CS). METHODS: A clinical medical record of 100 pregnant women undergoing rapid mass blood transfusion during sections from June 2019 to June 2021. According to the different nursing methods, patients divided into control group (n = 50) and observation group (n = 50). Among them, the control group implemented routine nursing, and the observation group implemented predictive nursing intervention based on the control group. Moreover, compared the differences in stress response, complications, and pain scores before and after the nursing of pregnant women undergoing rapid mass blood transfusion during CS. RESULTS: The anxiety and depression scores of pregnant women in the two groups were significantly improved after nursing, and the psychological stress response of the observation group was significantly lower than that of the control group (P < 0.05). The heart rate and mean arterial pressure (MAP) of the observation group during delivery were lower than those of the control group, and the MAP at the end of delivery was lower than that of the control group (P < 0.05). Moreover, different pain scores improved significantly in both groups, with the observation group considerably less than the control group (P < 0.05). After nursing, complications such as skin rash, urinary retention, chills, diarrhea, and anaphylactic shock in the observation group were 18%, which significantly higher than in the control group (4%) (P < 0.05). CONCLUSION: Predictive nursing intervention can effectively relieve the pain, reduce the incidence of complications, improve mood and stress response, and serve as a reference value for the nursing of women undergoing rapid mass transfusion during CS.

IL-10 protects against OPC ferroptosis by regulating lipid reactive oxygen species levels post stroke.

Accumulation of reactive oxygen species (ROS), especially on lipids, induces massive cell death in neurons and oligodendrocyte progenitor cells (OPCs) and causes severe neurologic deficits post stroke. While small compounds, such as deferoxamine, lipostatin-1, and ferrostatin-1, have been shown to be effective in reducing lipid ROS, the mechanisms by which endogenously protective molecules act against lipid ROS accumulation and subsequent cell death are still unclear, especially in OPCs, which are critical for maintaining white matter integrity and improving long-term outcomes after stroke. Here, using mouse primary OPC cultures, we demonstrate that interleukin-10 (IL-10), a cytokine playing roles in reducing neuroinflammation and promoting hematoma clearance, significantly reduced hemorrhage-induced lipid ROS accumulation and subsequent ferroptosis in OPCs. Mechanistically, IL-10 activated the IL-10R/STAT3 signaling pathway and upregulated the DLK1/AMPK/ACC axis. Subsequently, IL-10 reprogrammed lipid metabolism and reduced lipid ROS accumulation. In addition, in an autologous blood injection intracerebral hemorrhagic stroke (ICH) mouse model, deficiency of the endogenous Il-10, specific knocking out Il10r or Dlk1 in OPCs, or administration of ACC inhibitor was associated with increased OPC cell death, demyelination, axonal sprouting, and the cognitive deficits during the chronic phase of ICH and vice versa. These data suggest that IL-10 protects against OPC loss and white matter injury by reducing lipid ROS, supporting further development of potential clinical applications to benefit patients with stroke and related disorders.

Translation, cultural adaptation, and validation of the Chinese standardized outcomes in nephrology-hemodialysis fatigue (C-SONG-HD fatigue) scale: a study of Chinese patients undergoing hemodialysis.

OBJECTIVE: This study aimed to translate and culturally adapt the standardized outcomes in nephrology-hemodialysis fatigue (SONG-HD fatigue) scale and to assess the psychometric properties of the Chinese version of the SONG-HD fatigue (C-SONG-HD fatigue) scale. METHODS: Forward and back translations were used to translate the SONG-HD fatigue scale into Chinese. We used the C-SONG-HD fatigue scale to survey Chinese patients undergoing hemodialysis (HD) in China. We examined the distribution of responses and floor and ceiling effects. Cronbach's alpha and McDonald's omega coefficient, intraclass coefficients, and Spearman correlations were used to assess internal consistency reliability, test-retest reliability, and convergent validity, respectively. Responsiveness was also evaluated. RESULTS: In total, 489 participants across southeast China, northwest China, and central China completed the study. The C-SONG-HD fatigue scale had good internal consistency (Cronbach's alpha coefficient 0.861, omega coefficient 0.916), test-retest reliability (intraclass correlation coefficient 0.695), and convergent validity (Spearman correlation 0.691). The analysis of all first-time HD patients did not show notable responsiveness, and only patients with temporary vascular access had good responsiveness with an effect size (ES) of 0.54, a standardized response mean (SRM) of 0.85, and a standard error of measurement (SEM) of 0.77. CONCLUSION: The Chinese version of the SONG-HD fatigue scale showed satisfactory reliability and validity in patients undergoing hemodialysis (HD) in China. It could be used as a tool to measure the fatigue of Chinese HD patients.