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INTRODUCTION: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. METHODS: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. RESULTS: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. CONCLUSION: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.
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Estresse do Retículo Endoplasmático , Miócitos de Músculo Liso , Artéria Pulmonar , Piroptose , Estresse do Retículo Endoplasmático/fisiologia , Piroptose/fisiologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Animais , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , RNA Circular/metabolismo , RNA Circular/genética , Masculino , Células Cultivadas , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Proteínas de MembranaRESUMO
The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.
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Background: Restricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière's disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD. Methods: Summary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias. Results: The primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429-1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427-1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555-1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993-1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987-1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985-1.011; p = 0.72). Conclusion: This MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.
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This article analyzed the mechanism of Huangqi Simiao Decoction(HSD) for the treatment of type 2 diabetes mellitus(T2DM). The component targets of HSD and the related disease targets of T2DM were screened through network pharmacology. The protein-protein interaction(PPI) network of intersecting targets and the drug-component-intersecting target network were constructed to screen the potential active ingredients and targets. Molecular docking was performed using AutoDock Vina software to verify the interaction between potential components and core targets. The serum was tested by ultra performance liquid chromatography-tandem mass spectrometry, and multivariate statistical analyses, such as principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA), were used to search for the differential metabolites and related metabolic pathways of each group by combining with the MetaboAnalyst database. The same metabolic pathways were analyzed by combining the screened differential metabolites with the intersecting targets screened by network pharmacology. Network pharmacology showed that the nine core components of HSD for the treatment of T2DM were quercetin, kaempferol, stigmasterol, baicalein, ß-sitosterol, flavodoxin, canthaxanthin, canthaxanthin, berberine, and berberine, and the five core targets included AKT1, TP53, TNF, IL6, and VEGFA. Molecular docking showed that the core components bound well to the target genes. Metabolomics showed that a total of 112 common differential metabolites were identified, of which 88 metabolites exhibited increased concentration and 24 metabolites decreased concentration after treatment with HSD. Enrichment analysis showed that HSD regulated the body metabolism of patients with T2DM, mainly related to seven metabolic pathways, such as amino acid metabolism and tricarboxylic acid cycle. The joint analysis of metabolomics and network pharmacology showed that both involved histidine metabolism, arginine and proline metabolic pathways. This study suggests that HSD has a good efficacy for T2DM. Based on the combined analysis of metabolomics and network pharmacology, it was found that the mechanism may be that the pharmacodynamic bases of quercetin, kaempferol, and stigmasterol in HSD enhance the effects on histidine metabolism, arginine and proline metabolic pathways by modulating a variety of metabolites, which provides the basis for further prevention and treatment of T2DM.
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Diabetes Mellitus Tipo 2 , Medicamentos de Ervas Chinesas , Metabolômica , Farmacologia em Rede , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Solitary spinal metastasis (SM) is one of the indications for total en bloc spondylectomy (TES). Conventional TES carries the risk of damage to the great vessels anterior to the vertebral column, mainly because of a lack of visualization of the anterior structures. In this study, we devised a modified standard TES technique to achieve direct visualization in a 1-stage posterior approach. METHODS: Included in this study were patients ≥18 years old with solitary thoracic or lumbar SM who underwent the modified standard TES at our institution between January 2017 and October 2022. Patient data were retrospectively sourced from medical records, and patients had a minimum of 3 months of postoperative follow-up. RESULTS: This study involved 71 East Asian patients (median age, 57 years; 34 males), comprising 38 patients with thoracic SM and 33 with lumbar SM. Lung cancer was the most common tumor histology. Fourteen patients (19.7%) experienced intraoperative complications; pleural rupture was the predominant complication, and there were no cases of injury to the spinal cord or great vessels. The median operative time was 305 minutes (range, 203 to 660 minutes). The median intraoperative blood loss was 1,000 mL (range, 400 to 4,000 mL). The median perioperative blood transfusion was 4 units (range, 0 to 12 units), and the median hospitalization duration was 17 days (range, 14 to 29 days). Additionally, 27 patients (38.0%) had acute (perioperative) complications. Seven patients were lost to follow-up. Significant clinical improvement was achieved 3 months postoperatively. Postoperative early and late complications were observed in 5 patients. Of the 64 patients with completed follow-up, 47 (73.4%) had negative surgical margins, and none received postoperative radiation therapy. Revision surgery for local tumor recurrence was performed in 4.7% of patients. The median follow-up was 31.5 months (range, 3 to 81 months). CONCLUSIONS: Our modified standard TES was demonstrated to be a safe and effective surgical technique for solitary thoracolumbar SM. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation. CDNF moderates mitochondrial membrane potential, reactive oxygen species production, and intracellular calcium in activated platelets by interfering with GTP binding to Rap1b, thereby reducing Rap1b activation and downregulating the Rap1b-MAPK-PLA2 signaling pathway, which decreases release of the pro-inflammatory mediator thromboxane A2. In addition, CDNF reduces the inflammatory response in BV2 microglial cells co-cultured with activated platelets. Consistent with ex vivo findings, subcutaneous administration of CDNF in a rat model of ischemic stroke significantly reduces platelet activation, aggregation, lipid mediator production, infarct volume, and neurological deficits. In summary, our study highlights CDNF as a promising therapeutic target for mitigating platelet-induced inflammation and enhancing recovery in stroke. Harnessing the CDNF pathway may offer a novel therapeutic strategy for stroke intervention.
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Objective: Investigating the interaction between Mast cells (MCs) and Mononuclear Phagocytes (MPs) in the tumor microenvironment (TME) of blader cancer (BCa) to uncover potential immunotherapeutic targets. Methods: Single-cell RNA sequencing (scRNA-Seq) was conducted on 12 BCa patients to identify distinct subgroups of MCs and MPs. Transcriptome data was analyzed to characterize the phenotype, gene enrichment, cell-cell communication, and biological processes. The expression levels of cytokines were assessed by enzyme-linked immunosorbent assay (ELISA), while the chemotactic effects of cytokines were evaluated through Transwell assay. Results: In muscle-invasive bladder cancer (MIBC), the proportion of interferon-stimulated MC subtype (Mast-ISG15) increased. Mast-IL13 subgroup and Mast-CCL2 subgroups were functionally enriched in interferon (IFN) and nuclear factor kappa-B (NF-κB) signaling pathways. The Mast-CCL2 subgroup overexpressed the CCL2 gene, which could chemoattract MPs through CCL2. In vitro experiments confirmed that under stimulation, activated MCs activated IFN and NF-κB signaling, increasing the secretion of CCL2 and IL-13, chemoattracted THP-1 monocyte. Conclusion: This study revealed the vital role of MCs in shaping the TME of BCa. And provides new insights for the precise treatment of BCa.
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Integrated agriculture-aquaculture has emerged as a promising ecological development model. Crayfish, a popular aquaculture species, are traditionally reared either in monoculture ponds (mono-C) or in rice-crayfish polyculture system (poly-RC). In this study, we introduced a novel polyculture system by combining fruit tree with crayfish (poly-FC), aiming to compare these three crayfish culture modes in terms of production performance and ecological sustainability. The results indicated that crayfish reared in the two polyculture modes exhibited significantly higher specific growth rate and condition factor compared to those in mono-C. Crayfish cultured in poly-FC also showed better muscle quality and higher levels of crude fat and flavor or essential amino acids. Isotope mixing model showed that feed and benthic animals were the primary food sources of crayfish in mono-C, whereas aquatic plants, fruit litter or rice contributed more to those in polyculture modes. For greenhouse gas emissions, poly-FC mode emitted almost no CO2 and N2O even favored negative CH4 emission, while poly-RC and mono-C modes showed positive emissions of CH4 and CO2, respectively. Supported by metagenomics, the sink of CH4 in poly-FC was probably due to the lower mcr abundance but the higher pmo abundance in water. The low production and emission of N2O in poly-FC might result from the low-abundant Nitrospirae_bacterium and its coding gene norC in sediment, consistent with the lower denitrification rate but the higher NO3- concentration than mono-C. Overall, our findings reveal the superiority of polyculture of fruit tree with crayfish in terms of production performance and greenhouse gas emissions in the system.
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Introduction: Early identification of high-risk traumatic brain injury (TBI) patients is crucial for optimizing treatment strategies and improving outcomes. The C-reactive protein-to-lymphocyte ratio (CLR) reflects systemic immunology and inflammation function and serves as a new biomarker for patient stratification. This study aimed to assess the predictive value of the CLR for mortality in patients with isolated moderate to severe TBI. Methods: A retrospective analysis of trauma registry data from 2009 to 2022 was conducted, including 1641 adult patients with isolated moderate to severe TBI. Patient demographics, the CLR, injury characteristics, and outcomes were compared between deceased and surviving patients. Univariate and multivariate analyses were performed to identify mortality risk factors. The optimal CLR cut-off value for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Results: The CLR was significantly higher in deceased patients compared to survivors (60.1 vs. 33.9, p < 0.001). The optimal CLR cut-off value for predicting mortality was 54.5, with a sensitivity of 0.328 and a specificity of 0.812. The area under the ROC curve was 0.566, indicating poor discriminative ability. In the multivariate analysis, the CLR was not a significant independent predictor of mortality (OR 1.03, p = 0.051). After propensity score matching to attenuate the difference in baseline characteristics, including sex, age, comorbidities, conscious level, and injury severity, the high-CLR group (CLR ≥ 54.5) did not have significantly higher mortality compared to the low-CLR group (CLR < 54.5). Conclusion: While the CLR was associated with mortality in TBI patients, it demonstrated poor discriminative ability as a standalone predictor. The association between a high CLR and worse outcomes may be primarily due to other baseline patient and injury characteristics, rather than the CLR itself.
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In recent years, research on attribute-based encryption (ABE) has expanded into the quantum domain. Because a traditional single authority can cause the potential single point of failure, an improved lattice-based quantum-resistant identity authentication and policy attribute encryption scheme is proposed, in which the generation of random values is optimized by adjusting parameters in the Gaussian sampling algorithm to improve overall performance. Additionally, in the key generation phase, attributes are processed according to their shared nature, which reduces the computational overhead of the authorization authority. In the decryption phase, the basis transformation of the Lenstra-Lenstra-Lovász (LLL) lattice reduction algorithm is utilized to rapidly convert shared matrices into the shortest vector form, which can reduce the computational cost of linear space checks. The experimental results demonstrate that the proposed method not only improves efficiency but also enhances security compared with related schemes.
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PROBLEM: No studies have been conducted to examine the relationships between perceived stress, positive/negative dyadic coping, and prenatal depression symptoms in Chinese couples with gestational diabetes mellitus (GDM). BACKGROUND: GDM is a stressful event for pregnant women and their partners, which may result in clinically significant prenatal depression symptoms in couples. AIM: This study aims to examine the relationships and differences in perceived stress, positive/negative dyadic coping, and prenatal depression symptoms between Chinese pregnant women with GDM and their partners and to explore the mediating role of positive/negative dyadic coping. METHODS: A cross-sectional study was conducted in Guangzhou, China, from January to October 2021. 402 pairs of GDM couples completed the questionnaires, including the Edinburgh Postnatal Depression Scale, the Chinese version of the Dyadic Coping Inventory, and the Perceived Stress Scale. Dyadic data was analyzed using the actor-partner interdependence mediation model. FINDINGS: 37.6 % of pregnant women with GDM and 24.6 % of their partners experienced clinically significant prenatal depression symptoms. Depression symptoms in couples mutually influence each other. Perceived stress was directly or indirectly related to their and partners' prenatal depression symptoms in GDM couples, with negative dyadic coping acting as a mediator. Maternal negative dyadic coping was also a partner-mediator. DISCUSSION: The findings of the present study may provide healthcare professionals with a better understanding of the effect of the interpersonal interaction between the couples as a dyad on prenatal depression symptoms in Chinese context. CONCLUSION: There were intrapersonal and interpersonal associations among perceived stress, negative dyadic coping, and prenatal depression symptoms in pregnant women with GDM and their partners. It suggests a need for screening clinically significant prenatal depression symptoms and decreasing perceived stress and negative dyadic coping among couples with GDM with a focus on pregnant women with GDM.
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Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.
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Neoplasias da Mama , Movimento Celular , Proliferação de Células , Regulação para Baixo , Glicólise , Peptídeos e Proteínas de Sinalização Intracelular , Fator de Transcrição STAT3 , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Glicólise/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Movimento Celular/genética , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Apoptose/genética , Células MCF-7 , Espécies Reativas de Oxigênio/metabolismoRESUMO
Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.
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Anti-Inflamatórios , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Peixe-Zebra , Animais , Sulfato de Dextrana/efeitos adversos , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismoRESUMO
INTRODUCTION: Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. METHODS: A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. RESULTS: SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). CONCLUSION: SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival.
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Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis. The development of general and practical methods for the stereoselective construction of synthetically versatile P(III)-stereogenic phosphines is particularly appealing but remains elusive. Herein, we describe a nickel-catalyzed asymmetric alkylation of primary phosphines with alkyl halides for the synthesis of P-stereogenic secondary phosphine-boranes with high enantioselectivity and broad substrate scope. The resulting optically active secondary phosphine-boranes allow for further stereospecific transformations, thereby establishing a modular and efficient platform for the diversity-oriented construction of P-stereogenic phosphine compounds.
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BACKGROUND: The leakage of saliva through the deep neck region from a pharyngocutaneous fistula could cause devastating complications, including vascular ruptures leading to mortality. While a partial pharyngoesophageal defect is created after total laryngectomy, a patch pattern of hypopharyngeal reconstruction is required, for which a fasciocutaneous free flap is usually applied. If radiotherapy fails to cure pharyngeal cancer, salvage total laryngectomy (STL) is needed. However, postradiation tissues tend not to heal well, and the incidence of pharyngocutaneous fistula therefore increases. We proposed an edge-epithelialization method to address this problem and conducted a retrospective study for comparison. METHODS: The inclusion criteria were patients with head and neck cancer who underwent total laryngectomy that immediately required patch free flap reconstruction at a single medical center (January 2012-December 2021). Receipt of presurgical radiotherapy, hospitalization duration, and the presence of postoperative complications were recorded. RESULTS: The included patients were separated into two groups: Group A (edge de-epithelialization not adopted) (n = 79) and Group B (edge de-epithelialization adopted) (n = 51). Forty-four and twenty-two patients in Groups A and Group B, respectively, received preoperative radiotherapies and simultaneous STL and fasciocutaneous free flap reconstructions. The incidence of pharyngocutaneous fistula was significantly lower in Group B (p = 0.0145). This phenomenon was the same for patients who underwent preoperative radiotherapy only (p = 0.0470) but not for patients who did not receive preoperative radiotherapy (p = 0.2363). CONCLUSIONS: Edge de-epithelialization is an effective method for reducing pharyngocutaneous fistula formation in patch free flap reconstructions after STLs.
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BACKGROUND: Sleep regularity has been linked to a risk of arterial stiffness (AS). However, the association between sleep regularity indicators, which reflect 24-hour sleep variability, and AS has not yet been examined. METHODS: We analyzed data from 516 adults, aged 40-65 years (the median age of 51 years), from the 'Follow-up Study of Sleep Characteristics and Chronic Diseases in the Middle-aged and Elderly Population in Guizhou Province'. Participants underwent assessments of AS (OMRON HBP-8000, baPWV ≥ 1400 cm/s) and sleep (wrist smart band (Honor band 5i) for ≥ 7 days). Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between sleep regularity and AS. RESULTS: A total of 516 people were included in this study, of which 279 (54.07%) were in the AS group. The univariate results showed that the AS group (Median 71.18) had lower SRI compared to the No-AS group (Median 75.00) (p < 0.001). The multifactorial results showed participants with higher SRI scores were more likely to have a lower risk of AS compared to those with lower SRI scores (ORQ4 VS. Q1=0.46, 95%CI: 0.25-0.85, p = 0.013). The SRI effect was more pronounced in male (ORQ4 VS. Q1=0.28, 95%CI: 0.12-0.69, p = 0.005), snoring populations (ORQ4 VS. Q1=0.13, 95%CI: 0.04-0.48, p = 0.002), and non-retired populations (ORQ4 VS. Q1=0.45, 95%CI: 0.22-0.92, p = 0.028). CONCLUSIONS: The present findings indicated that the effect between SRI and AS may be more sensitive than the standard deviation of sleep duration as well as the standard deviation of sleep onset.
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Rigidez Vascular , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Feminino , Adulto , Idoso , Rigidez Vascular/fisiologia , Sono/fisiologia , Fatores de Risco , SeguimentosRESUMO
Tellurium is a rare element, and ammonium trichloro (dioxoethylene-o,o') tellurate (AS101) is the most bioactive molecule among several synthetic tellurium compounds. AS101 was found to be immunomodulatory and can modulate types of cytokines. However, the effect of AS101 on tumor metastasis remains unclear. Heparanase, an endo-glucuronidase, cleaves heparin sulfate side chains of proteoglycans on the cell surface, further leading to the degradation of the extracellular matrix. Heparanase also releases angiogenic factors in the extracellular matrix, is overexpressed in tumor cells, and promotes tumor metastasis and angiogenesis. In this study, we investigated the effect of AS101 in 4T1 and CT26 cells, especially heparanase. Heparanase expression was downregulated in 4T1 and CT26 cells after treatment with AS101 in vitro. The protein level involved in the protein kinase-B/mammalian target of rapamycin (AKT/mTOR) signaling pathway also declined. Cell migration assays revealed the inhibitory effect of AS101 on migration. The results of this study indicate that AS101 inhibits tumor migration by downregulating heparanase through the AKT/mTOR signaling pathway and has positive effects in vivo.
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BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. AIM: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. METHODS: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. RESULTS: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a ß of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (ß = 0.0078, 95%CI: 0.0052-0.0104) and ALT (ß = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. CONCLUSION: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.
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Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.