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Artificial tracheal substitutes encounter significant challenges during long-segmental tracheal defects (LSTD) reconstruction, notably early postoperative anastomotic stenosis and tracheal chondromalacia. Mitigating early anastomotic stenosis by creating a compliant sutureless substitute is pivotal. Enhancing its chondrogenic capacity is equally critical for sustained healthy tracheal cartilage regeneration. This study proposes a self-healing hydrogel for sutureless tracheal anastomosis to mitigate anastomotic stenosis, enriched with kartogenin (KGN) and transforming growth factor-ß1 (TGFß1) to bolster chondrogenic properties. Initially, two precursor solutions were prepared: 1) aldehyde-modified hyaluronic acid with sulfonation and ß-cyclodextrin-CHO loaded with KGN; 2) hydrazide-grafted gelatin loaded with TGFß1. Coextrusion of these solutions resulted in a gelated G + TGFß1/sH-CD + KGN hydrogel, characterized by a robust covalent bonding network of acylhydrazones between hydrazide and aldehyde groups, imparting excellent self-healing properties. The G + TGFß1/sH-CD + KGN hydrogels, showcasing favorable cytocompatibility, excellent injectability, and rapid gelation, were loaded with bone marrow stem cells. These were customized into O-shaped rings and assembled into a malleable tracheal substitute using our established ring-to-tube method. This resultant compliant substitute facilitated sutureless anastomosis of LSTD in a rabbit model, attributed to the Schiff base reaction between the hydrogel's carbonyl group and the tissue's amino group. Notably, the tracheal substitute reduced early postoperative anastomotic stenosis, maintained tracheal patency, alleviated sputum blockage, promoted reepithelization, and increased the survival rate of the experimental rabbits. The sustained release of chondrocytokines resulted in excellent tracheal cartilage regeneration. Employing chondrocytokines-loaded hydrogels with self-healing properties represents a significant advancement in sutureless tracheal anastomosis and tracheal cartilage regeneration, holding promising potential in inhibiting early postoperative anastomotic stenosis and tracheal chondromalacia when treating LSTD.
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INTRODUCTION: Overactive bladder (OAB) affects approximately 500 million people worldwide, with a higher prevalence in women than in men, significantly impacting the quality of life of female patients. Treatment options for OAB are currently limited. Previous research has proposed that electroacupuncture could be a viable treatment for OAB in women, but there is a lack of high-quality clinical evidence. This study aims to evaluate the effectiveness of electroacupuncture as a safe and efficient non-pharmacological treatment for female OAB by comparing it with solifenacin succinate. METHODS AND ANALYSIS: This study is a multicentre, single-blind, double-dummy randomised controlled non-inferiority clinical trial involving 204 eligible female participants with OAB. Participants will be randomly assigned in a 1:1 ratio to either the electroacupuncture group (receiving electroacupuncture and placebo) or the solifenacin succinate group (receiving sham electroacupuncture and solifenacin succinate). Each participant will undergo 12 sessions of electroacupuncture (or sham electroacupuncture) treatment and solifenacin succinate (or placebo) treatment over a 4-week period. The primary outcome measure will be the percentage change in the number of micturition episodes every 24 hours at week 4 compared with baseline. Secondary outcomes will include a percentage reduction in the number of micturition episodes every 24 hours at 2th, 8th and 16th weeks of the trial, Overactive Bladder Symptom Score, number of urinary incontinence and urgency episodes every 24 hours based on a 3-day voiding diary, OAB Questionnaire, Generalised Anxiety Disorder Scale-7, King's Health Questionnaire and Participant Self-evaluation of Therapeutic Effects. Adverse events will be monitored throughout the study. Efficacy analyses will be conducted on both the intention-to-treat population and the per-protocol set population. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Ethics Committee of Longhua Hospital Shanghai University of Traditional Chinese Medicine (approval number: 2022LCSY097). Each participant will sign a written informed consent before randomisation. The results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER : NCT05798403.
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Electroacupuntura , Antagonistas Muscarínicos , Succinato de Solifenacina , Vejiga Urinaria Hiperactiva , Humanos , Succinato de Solifenacina/uso terapéutico , Vejiga Urinaria Hiperactiva/terapia , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Femenino , Electroacupuntura/métodos , Antagonistas Muscarínicos/uso terapéutico , Adulto , Persona de Mediana Edad , Calidad de Vida , Método Simple Ciego , Estudios Multicéntricos como Asunto , Resultado del Tratamiento , Estudios de Equivalencia como Asunto , Agentes Urológicos/uso terapéutico , AncianoRESUMEN
Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatments for non-small cell lung cancer (NSCLC) patients without driver mutations. However, a considerable proportion of patients suffer from severe immune side effects and fail to respond to ICIs. As effective biomarkers, programmed cell death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) require invasive procedures that place heavy physical and psychological burdens on patients. This study aims to identify simple and effective markers to optimize patient selection through therapeutic decisions and outcome prediction. Methods: This retrospective study comprised 95 patients with metastatic NSCLC who were treated with ICIs either as the standard of care or in a clinical trial. The following data were extracted from the medical records. The baseline and dynamic neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated in the present study. Responses were assessed by computed tomography (CT) imaging and classified according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 every 6-12 weeks during treatment. Results: In total, 95 patients were included in the present study. The median age of patients was 61 years, 83.2% (79/95) patients were male, 62.1% (59/95) were former or current smokers, 66.3% (63/95) had adenocarcinoma, 93.7% (89/95) had stage IV disease, and 87.4% were without molecular alterations. A higher overall response rate (ORR) and prolonged median progression-free survival (PFS) was observed in patients with a lower cycle 3 (C3) NLR [7.7 vs. 5.5 months, hazard ratio (HR): 1.70, 95% confidence interval (CI): 0.90-3.22; P=0.12] and derived NLR (dNLR) (8.2 vs. 5.6 months, HR: 1.67, 95% CI: 0.94-2.97; P=0.08). After two cycles of ICI treatment, patients who had an increased NLR, dNLR, and PLR had a lower ORR and an inferior median PFS than those with a decreased NLR (5.5 vs. 8.5 months, HR: 1.87, 95% CI: 1.09-3.21; P=0.02), dNLR (5.6 vs. 8.4 months, HR: 1.49, 95% CI: 0.87-2.57; P=0.15), and PLR (11.8 vs. 5.5 months, HR: 2.28, 95% CI: 1.32-3.94; P=0.003). Moreover, patients with both an increased NLR and PLR had a worse ORR and median PFS than those with either an increased NLR or PLR, or both an increased NLR and PLR (11.8 vs. 5.5 vs. 5.6 months, P=0.003). In addition, the dynamic changes in the PLR could serve as an independent predictive factor of PFS in NSCLC patients treated with ICIs. Conclusions: Elevated dynamic changes in the NLR and PLR were associated with lower response rates and shorter PFS in the patients with NSCLC treated with ICIs. Our results also highlight the role of dynamic changes in the PLR in identifying patients with NSCLC who could benefit from ICIs.
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Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.
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The deposition of lithium ions in an uneven manner can lead to the formation of lithium dendrites, which can puncture the battery separator and cause a short circuit. Additionally, intermediate polysulfides can shuttle between the separator, resulting in damage to the capacity of lithium-sulfur batteries and corrosion of the negative electrode. It is crucial to address these issues promptly. Hence, we developed a modified separator using nano-molybdenum powder, which effectively inhibits the growth of lithium dendrites and suppresses the shuttle effect of polysulfides. The modified separator extends the lifetime of the lithium metal anode, and the uniform pore distribution of the molybdenum powder facilitates the uniform diffusion of Li+ ions, thereby slowing down the detrimental effects. As a result, Li-S cells equipped with the nano-molybdenum powder modified separator achieve a remarkable capacity of 802 mA h g-1 at a current density of 0.5C and maintain a capacity of up to 614 mA h g-1 after 200 cycles.
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Loffler endocarditis is a rare disease associated with high mortality rates, therefore early diagnosis and prompt treatment are crucial factors in managing this condition effectively. The clinical manifestations are nonspecific which can lead to misdiagnosis easily. Here we report a case of rare idiopathic hypereosinophilic syndrome with Loffler endocarditis as the first presentation, first suspected acute coronary syndrome, diagnosed correctly by cardiac ultrasound. The purpose is to improve our understanding of the ultrasound manifestations of this disease.
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The immunosuppressive tumor microenvironment (TME) in solid tumors often impedes the efficacy of immunotherapy. Bacterial outer membrane vesicles (OMVs), as a promising cancer vaccine that can potently stimulate immune responses, have garnered interest as a potential platform for cancer therapy. However, the low yield of OMVs limits their utilization. To address this limitation, we developed a novel approach to synthesize OMV-like multifunctional synthetic bacterial vesicles (SBVs) by pretreating bacteria with ampicillin and lysing them through sonication. Compared to OMVs, the yield of SBVs increased by 40 times. Additionally, the unique synthesis process of SBVs allows for the encapsulation of bacterial intracellular contents, endowing SBVs with the capability of delivering catalase (CAT) for tumor hypoxia relief and activating the host cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. To overcome the toxicity of lipopolysaccharide (LPS) on the SBVs surface, we decorated SBVs with a biocompatible polydopamine (PDA) shell, which allowed TME reprogramming using SBVs to be conducted without adverse side effects. Additionally, the photosensitizer indocyanine green (ICG) was loaded into the PDA shell to induce immunogenic cell death and further improve the efficacy of immunotherapy. In summary, the SBVs-based therapeutic platform SBV@PDA/ICG (SBV@P/I) can synergistically elicit safe and potent tumor-specific antitumor responses through combined immunotherapy and phototherapy.
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With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8-14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1-5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96-12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57-8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06-16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50-0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19-0.51), and NWCO (PAF: 0.13, 95% CI: 0.03-0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.
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Hipertensión , Humanos , Estudios Transversales , Masculino , Femenino , Hipertensión/epidemiología , China/epidemiología , Niño , Prevalencia , Adolescente , Factores de Riesgo , Modelos Logísticos , Bosques AleatoriosRESUMEN
Diurnal floret opening time (DFOT) is a pivotal trait for successful fertilization and hybrid breeding in rice. However, the molecular mechanism underlying this trait is poorly understood in rice. In this study, we combined the cytological, genetic and molecular studies to demonstrate that jasmonic acid (JA) regulates DFOT in rice through modulating the turgor and osmotic pressure of the lodicules. We show that lodicules undergo dramatic morphologic changes, accompanied by changes in water and sugar contents during the process of floret opening. Consistently, a large set of genes associated with cell osmolality and cell wall remodeling exhibits distinct expression profiles at different time points in our time-course transcriptomes of lodicules. Notably, a group of JA biosynthesis and signaling genes is continuously upregulated, accompanied by a gradual increase in JA accumulation as floret opening approaching. Furthermore, we demonstrate that the JA biosynthesis gene OsAOS1 is required for endogenous JA biosynthesis in lodicules and promoting rice DFOT. Moreover, OsMYC2, a master regulator of JA signaling, regulates rice DFOT by directly activating OsAOS1, OsSWEET4, OsPIP2;2 and OsXTH9. Collectively, our findings establish a core regulatory network mediated by JA for modulating rice DFOT and provide effective gene targets for the genetic improvement of DFOT in rice.
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Ritmo Circadiano , Ciclopentanos , Regulación de la Expresión Génica de las Plantas , Redes Reguladoras de Genes , Oryza , Oxilipinas , Proteínas de Plantas , Oryza/genética , Oryza/fisiología , Oryza/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiología , Flores/fisiología , Flores/genética , Transducción de Señal , Genes de Plantas , Presión Osmótica , Factores de Tiempo , Agua/metabolismo , Transcriptoma/genéticaRESUMEN
Glaucoma is a degenerative disease characterized by retinal ganglion cell (RGC) death and visual impairment caused by elevated intraocular pressure (IOP). Elevated IOP can activate microglia, which participate in ganglion cell injury. Based on the study of caveolin-1 (Cav-1) in glaucoma, we aimed to explore the effect and mechanism of Cav-1 on RGC apoptosis in mice with acute ocular hypertension (AOH). AOH mice were established, and Cav-1 was intravitreally injected. Retinal microglia and RGCs were isolated from neonatal mice. TUNEL staining, hematoxylin-eosin staining, immunohistochemistry, flow cytometry, PCR and western blotting were used to observe the effect of Cav-1 on RGCs and mouse retinas. The thickness of the whole retina and the inner retinal sublayer decreased significantly, retinal cell apoptosis increased after AOH injury, and Cav-1 treatment reversed the effect of AOH injury. In addition, Cav-1 treatment promoted the conversion of proinflammatory M1 microglia to anti-inflammatory M2 microglia. Microglia and RGCs were isolated from neonatal mice. Cav-1 protects RGCs from OGD/R-induced injury by changing the polarization status of retinal microglia in vitro. Further studies revealed that Cav-1 activated the Akt/PTEN signaling pathway and inhibited TLR4. Our study provides evidence that Cav-1 may be a promising therapeutic target for glaucoma.
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Caveolina 1 , Glaucoma , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Células Ganglionares de la Retina , Transducción de Señal , Receptor Toll-Like 4 , Animales , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/efectos de los fármacos , Caveolina 1/metabolismo , Transducción de Señal/fisiología , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Glaucoma/metabolismo , Glaucoma/patología , Receptor Toll-Like 4/metabolismo , Ratones Endogámicos C57BL , Apoptosis/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Modelos Animales de EnfermedadRESUMEN
Metal lithium negative electrodes are considered the "holy grail" of lithium battery negative electrodes due to their ultra-high energy density and low overpotential. However, the arbitrary growth of lithium dendrites during the cycling process hindered its industrialization process. We prepared porous carbon doped with zinc oxide nanoparticles (ZNC-MOF-5) by high-temperature carbonization of MOF-5, and coated ZNC-MOF-5 on the surface of commercial membranes (ZNC-MOF-5@PP). Used to improve the cycling stability of metal lithium negative electrodes. Zinc oxide nanoparticles in ZNC-MOF-5 have good lithium affinity and can promote Li+ deposition. The porous structure with a high specific surface area endows the electrode with high lithium loading capacity, reduces local current density, and obtains a dendrite-free metal lithium negative electrode. The electrochemical cycling performance of Li/Cu batteries indicates that, ZNC-MOF-5@PP. The separator can prevent the growth of dendrites and improve cycling stability, proving that ZNC-MOF-5 can effectively guide the deposition of Li and solve dendrite problems.
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KEY MESSAGE: This study provided a non-destructive detection method with Vis-NIR hyperspectral imaging combining with physio-biochemical parameters in Helianthus annuus in response to Orobanche cumana infection that took insights into the monitoring of sunflower weed. Sunflower broomrape (Orobanche cumana Wallr.) is an obligate weed that attaches to the host roots of sunflower (Helianthus annuus L.) leading to a significant reduction in yield worldwide. The emergence of O. cumana shoots after its underground life-cycle causes irreversible damage to the crop. In this study, a fast visual, non-invasive and precise method for monitoring changes in spectral characteristics using visible and near-infrared (Vis-NIR) hyperspectral imaging (HSI) was developed. By combining the bands sensitive to antioxidant enzymes (SOD, GR), non-antioxidant enzymes (GSH, GSH + GSSG), MDA, ROS (O2-, OH-), PAL, and PPO activities obtained from the host leaves, we sought to establish an accurate means of assessing these changes and conducted imaging acquisition using hyperspectral cameras from both infested and non-infested sunflower cultivars, followed by physio-biochemical parameters measurement as well as analyzed the expression of defense related genes. Extreme learning machine (ELM) and convolutional neural network (CNN) models using 3-band images were built to classify infected or non-infected plants in three sunflower cultivars, achieving accuracies of 95.83% and 95.83% for the discrimination of infestation as well as 97.92% and 95.83% of varieties, respectively, indicating the potential of multi-spectral imaging systems for early detection of O. cumana in weed management.
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Helianthus , Imágenes Hiperespectrales , Orobanche , Helianthus/parasitología , Orobanche/fisiología , Imágenes Hiperespectrales/métodos , Espectroscopía Infrarroja Corta/métodos , Hojas de la Planta/parasitología , Hojas de la Planta/metabolismo , Enfermedades de las Plantas/parasitología , Antioxidantes/metabolismo , Malezas , Interacciones Huésped-ParásitosRESUMEN
Breast cancer remains one of the predominant malignancies worldwide. In the context of inoperable advanced or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer, systemic management primarily relies on HER2-targeting monoclonal antibodies. With the successful development of anti-HER2 antibody-drug conjugates (ADCs), these agents have been increasingly integrated into therapeutic regimens for metastatic breast cancer. Here, we present the case of a 42-year-old female patient with HER2-positive pulmonary metastatic breast cancer who underwent an extensive treatment protocol. This protocol included chemotherapy, radiation therapy, hormonal therapy, surgical intervention on the breast, and anti-HER2 therapies. The anti-HER2 therapies involved both singular and dual targeting strategies using trastuzumab and the ADC disitamab vedotin (RC48) over an 8-year period. After experiencing disease progression following HER2-targeted therapy with RC48, the patient achieved noticeable partial remission through a therapeutic regimen that combined trastuzumab deruxtecan (DS8201) and tislelizumab. The data suggest a promising role for DS8201 in managing advanced stages of HER2-amplified metastatic breast cancer, especially in cases that demonstrate progression after initial HER2-directed therapies using ADCs. Furthermore, its combination with anti-PD-1 agents enhances therapeutic efficacy by augmenting the anti-tumoral immune response.
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BACKGROUND AND AIMS: The liver possesses a remarkable regenerative capacity in response to injuries or viral infections. Various growth factors and cytokines are involved in regulating liver regeneration. Prostaglandin D 2 , a pro-resolution lipid mediator, is the most abundant hepatic prostanoid. However, the role of prostaglandin D 2 in the injury-induced liver regeneration remains unclear. APPROACH AND RESULTS: Two-thirds partial hepatectomy (70% PH), massive hepatectomy (85% resection), and carbon tetrachloride-induced chronic injury were performed in mice to study the mechanisms of live regeneration. Hepatic prostaglandin D 2 production was elevated in mice after PH. Global deletion of D prostanoid receptor (DP) 1, but not DP2, slowed PH-induced liver regeneration in mice, as evidenced by lower liver weight to body weight ratio, less Ki67 + hepatocyte proliferation, and G2/M phase hepatocytes. In addition, DP1 deficiency, specifically in resident KCs, and not in endothelial cells or HSCs, retarded liver regeneration in mice after PH. Conversely, the overexpression of exogenous DP1 in KCs accelerated liver regeneration in mice. Mechanistically, DP1 activation promoted Wnt2 transcription in a PKA/CREB-dependent manner in resident KCs and mediated hepatocyte proliferation through Frizzled8/ß-catenin signaling. Adeno-associated virus vector serotype 8-mediated Frizzled8 knockdown in hepatocytes attenuated accelerated liver regeneration in KC-DP1 transgenic mice after PH. Treatment with the DP1 receptor agonist BW245C promotes PH-induced liver regeneration in mice. CONCLUSIONS: DP1 activation mediates crosstalk between KCs and hepatocytes through Wnt2 and facilitates liver regeneration. Hence, DP1 may serve as a novel therapeutic target in acute and chronic liver diseases.
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OBJECTIVE: The purpose of this study was to evaluate the pharmacovigilance and clinical characteristics of psychiatric adverse events(AEs) related to Fluoroquinolones(FQs), and to determine the risk factors for timely management. METHODS: Data about AE reporting comes from the FDA Adverse Event Reporting System (FAERS) database, which was used for pharmacovigilance assessments. In addition, we also analyzed the cases of psychiatric AEs related to FQs retrospectively. RESULTS: Both of the FAERS database analysis and literature reports show that the proportion of FQs-related psychiatric AEs reported in females were higher (51.11% VS 33.44% and 53.23% VS 46.77%). Both of them show that the proportion of psychiatric AEs caused by FQs was higher in the age groups of 19-44 (28.08% and 40.32%) and 45-64 (28.17% and 25.81%). Most psychiatric AEs occurred within 10 days after FQs administration. Literature shows that 67.74% of the psychiatric AEs disappeared within 3 days after drug withdrawal (some cases were accompanied by other drug). CONCLUSION: Psychiatric AEs caused by FQs are serious, and there are many important safety signals that have not been mentioned in the label or previous studies. It is very important to identify and manage psychiatric AEs in time for the safe use of FQs.
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Astrocyte-elevated gene-1 (AEG-1/MTDH/LYRIC) has garnered signficant attention in cancer research, yet, its role in inflammation-associated astrogliosis remains underexplored. This study aims to elucidate the effects of AEG-1 on reactive astrogliosis, including proliferation, migration, and glutamate uptake in primary astrocytes derived from rats. We first confirmed the effect of AEG-1 on these parameters. Subsequently, we investigated whether AEG-1 plays a role in the process of pro-inflammation factors such as tumor necrosis factor-alpha (TNF-α) induced astrogliosis. Our findings revealed that AEG-1-lentivirus infection led to hypertrophic cell bodies and enhanced expression of astrogliosis markers, including glial fibrillary acidic protein (GFAP) and vimentin. Additionally, AEG-1 was found to upregulate the mRNA and protein expression levels of EAAT2, a major glutamate transporter in the brain predominantly expressed by astrocytes and responsible for 90% of glutamate clearance. Furthermore, TNF-α was shown to promote astrogliosis, as well as astrocyte proliferation and migration, by upregulating AEG-1 expression through the NF-κB pathway. Collectively, these results suggest a potential role for AEG-1 in inflammation-related astrogliosis.
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Astrocitos , Gliosis , Proteínas de la Membrana , FN-kappa B , Proteínas de Unión al ARN , Factor de Necrosis Tumoral alfa , Regulación hacia Arriba , Animales , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , FN-kappa B/metabolismo , Gliosis/metabolismo , Gliosis/patología , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Ratas , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ratas Sprague-Dawley , Transducción de Señal , Células Cultivadas , Transportador 2 de Aminoácidos Excitadores/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Ácido Glutámico/metabolismoRESUMEN
BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.
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DNA damage-inducible transcript 3 (DDIT3) is a transcription factor central to apoptosis, differentiation, and stress response. DDIT3 has been extensively studied in cancer biology. However, its precise implications in breast cancer progression and its interaction with the immune microenvironment are unclear. In this study, we utilized a novel multi-omics integration strategy, combining bulk RNA sequencing, single-cell sequencing, spatial transcriptomics and immunohistochemistry, to explore the role of DDIT3 in breast cancer and establish the correlation between DDIT3 and poor prognosis in breast cancer patients. We identified a robust prognostic signature, including six genes (unc-93 homolog B1, TLR signaling regulator, anti-Mullerian hormone, DCTP pyrophosphatase 1, mitochondrial ribosomal protein L36, nuclear factor erythroid 2, and Rho GTPase activating protein 39), associated with DDIT3. This signature stratified the high-risk patient groups, characterized by increased infiltration of the regulatory T cells and M2-like macrophages and fibroblast growth factor (FGF)/FGF receptor signaling activation. Notably, the high-risk patient group demonstrated enhanced sensitivity to immunotherapy, presenting novel therapeutic opportunities. Integrating multi-omics data helped determine the spatial expression pattern of DDIT3 in the tumor microenvironment and its correlation with immune cell infiltration. This multi-dimensional analysis provided a comprehensive understanding of the intricate interplay between DDIT3 and the immune microenvironment in breast cancer. Overall, our study not only facilitates understanding the role of DDIT3 in breast cancer but also offers innovative insights for developing prognostic models and therapeutic strategies. Identifying the DDIT3-related prognostic signature and its association with the immune microenvironment provided a promising avenue for personalized breast cancer treatment.
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Tinea capitis, primarily caused by dermatophytes such as Trichophyton and Microsporum species, is a superficial fungal infection affecting the scalp and hair, commonly observed in prepubertal children but rare in adults. Here we report a unique case of an adult female with tinea capitis presenting as diffused alopecia and erythema inflammation on the scalp's apex, mimicking seborrheic dermatitis. Examination of the hair and scalp using fluorescence microscopy and fungal culture identified the presence of hyphae from Malassezia globosa, Malassezia furfur and Microsporum canis. The patient underwent with oral antifungal treatment for 3 months, resulting in the resolution of the rash and subsequent hair regrowth, with no recurrence during 6-month follow-up. In vitro co-culture experiments of Microsporum canis and Malassezia (both Malassezia globose and Malassezia furfur) revealed that Malassezia appears to facilitate Microsporum canis growth, while the reverse was not observed. This data suggests that Malassezia's use of long-chain fatty acids by might reduce its antibacterial effect, potentially aiding adult tinea capitis development caused by Microsporum canis.