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1.
Mol Pharm ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951109

RESUMEN

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

2.
Mol Cell Biochem ; 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38985252

RESUMEN

Cardiovascular disease (CVD) stands as a predominant global cause of morbidity and mortality, necessitating effective and cost-efficient therapies for cardiovascular risk reduction. Mitochondrial coupling factor 6 (CF6), identified as a novel proatherogenic peptide, emerges as a significant risk factor in endothelial dysfunction development, correlating with CVD severity. CF6 expression can be heightened by CVD risk factors like mechanical force, hypoxia, or high glucose stimuli through the NF-κB pathway. Many studies have explored the CF6-CVD relationship, revealing elevated plasma CF6 levels in essential hypertension, atherosclerotic cardiovascular disease (ASCVD), stroke, and preeclampsia patients. CF6 acts as a vasoactive and proatherogenic peptide in CVD, inducing intracellular acidosis in vascular endothelial cells, inhibiting nitric oxide (NO) and prostacyclin generation, increasing blood pressure, and producing proatherogenic molecules, significantly contributing to CVD development. CF6 induces an imbalance in endothelium-dependent factors, including NO, prostacyclin, and asymmetric dimethylarginine (ADMA), promoting vasoconstriction, vascular remodeling, thrombosis, and insulin resistance, possibly via C-src Ca2+ and PRMT-1/DDAH-2-ADMA-NO pathways. This review offers a comprehensive exploration of CF6 in the context of CVD, providing mechanistic insights into its role in processes impacting CVD, with a focus on CF6 functions, intracellular signaling, and regulatory mechanisms in vascular endothelial cells.

3.
Acad Radiol ; 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38918153

RESUMEN

RATIONALE AND OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) combined with immune-inflammatory markers in predicting axillary lymph node metastasis (ALNM) in breast cancer patients. METHODS: From January 2020 to June 2023, the clinicopathological data and ultrasound features of 401 breast cancer patients who underwent biopsy or surgery were recorded. Patients were randomly divided into a training set (321 patients) and a validation set (80 patients). The risk factors for ALNM were determined using univariate, least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression analysis, and prediction models were constructed. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess their diagnostic performance. RESULTS: Logistic regression analysis demonstrated that systemic immunoinflammatory index (SII), CA125, Ki67, pathological type, lesion size, enhancement pattern and Breast Imaging Reporting and Data System (BI-RADS) category were significant risk factors for ALNM. Three different models were constructed, and the combined model yielded an AUC of 0.903, which was superior to the clinical model (AUC=0.790) and ultrasound model (AUC=0.781). A nomogram was constructed based on the combined model, calibration curves and DCA demonstrated its satisfactory performance in predicting ALNM. CONCLUSION: The nomogram combining ultrasound features and immune-inflammatory markers could serve as a valuable instrument for predicting ALNM in breast cancer patients. DATA AVAILABILITY STATEMENT: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.

4.
ACS Appl Mater Interfaces ; 16(23): 29600-29609, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38832656

RESUMEN

Hydrogel tubes made of sodium alginate (SA) have potential applications in drug delivery, soft robots, biomimetic blood vessels, tissue stents, and other fields. However, the continuous preparation of hollow SA hydrogel tubes with good stability and size control remains a huge challenge for chemists, material scientists, and medical practitioners. Inspired by the plant apical growth strategy, a new method named soft cap-guided growth was proposed to produce SA hydrogel tubes. Due to the introduction of inert low gravity substances, such as air and heptane, into the extrusion needle in front of calcium chloride solution to form a soft cap, the SA hydrogel tubes with controllable sizes were fabricated rapidly and continuously without using a template through a negative gravitropism mechanism. The SA hydrogel tubes had good tensile strength, high burst pressure, and good cell compatibility. In addition, hydrogel tubes with complex patterns were conveniently created by controlling the motion path of a soft cap, such as a rotating SA bath or magnetic force. Our research provided a simple innovative technique to steer the growth of hydrogel tubes, which made it possible to mass produce hydrogel tubes with controllable sizes and programmable patterns.


Asunto(s)
Alginatos , Hidrogeles , Alginatos/química , Hidrogeles/química , Resistencia a la Tracción
5.
ACS Nano ; 18(24): 15590-15606, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38847586

RESUMEN

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.


Asunto(s)
Medios de Contraste , Ultrasonografía , Medios de Contraste/química , Medios de Contraste/farmacología , Humanos , Animales , Ratones , Nanopartículas/química , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Imagen Óptica , Gases/química , Línea Celular Tumoral , Femenino , Ratones Desnudos
6.
Angew Chem Int Ed Engl ; : e202408218, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38923694

RESUMEN

Photorechargeable zinc ion batteries (PZIBs), which can directly harvest and store solar energy, are promising technologies for the development of a renewable energy society. However, the incompatibility requirement between narrow band gap and wide coverage has raised severe challenges for high-efficiency dual-functional photocathodes. Herein, half-metallic vanadium (III) oxide (V2O3) was first reported as a dual-functional photocathode for PZIBs. Theoretical and experimental results revealed its unique photoelectrical and zinc ion storage properties for capturing and storing solar energy. To this end, a synergistic protective etching strategy was developed to construct carbon superstructure-supported V2O3 nanospheres (V2O3@CSs). The half-metallic characteristics of V2O3, combined with the three-dimensional superstructure assembled by ultrathin carbon nanosheets, established rapid charge transfer networks and robust framework for efficient and stable solar-energy storage. Consequently, the V2O3@CSs photocathode delivered record zinc ion storage properties, including a photo-assisted discharge capacities of 463 mAh∙g-1 at 2.0 A∙g-1 and long-term cycling stability over 3000 cycles. Notably, the PZIBs assembled using V2O3@CSs photocathodes could be photorecharged without an external circuit, exhibiting a high photo conversion efficiency (0.354%) and photorecharge voltage (1.0 V). This study offered a promising direction for the direct capture and storage of solar energy.

7.
Postgrad Med ; : 1-10, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38912905

RESUMEN

OBJECTIVES: To investigate the association between lipid ratios and survival outcomes in patients with locally advanced breast cancer (LABC) undergoing neoadjuvant chemotherapy. METHOD: This retrospective study included patients with LABC receiving neoadjuvant chemotherapy. Serum lipid levels were prospectively measured at baseline. Associations of triglyceride to total cholesterol (TG/TC), triglyceride to high-density lipoprotein (TG/HDL) and triglyceride to low-density lipoprotein (TG/LDL) ratios with prognosis were evaluated. RESULTS: Patients with high TG/TC (adjusted hazard ratio [aHR] = 2.47, 95% CI: 1.10, 5.56, p = 0.029), TG/HDL (aHR = 2.73, 95% CI: 1.16, 6.41, p = 0.021) and TG/LDL (aHR = 2.50, 95% CI: 1.11, 5.65, p = 0.027) ratios were more likely to experience disease-free survival (DFS) events. Subgroup analysis suggested that the prognostic impact of lipid ratios was more pronounced in patients with negative HER2 status or those at a high risk of recurrence (e.g. clinical stage III, Ki67 > 30%). Additionally, higher lipid ratios tended to indicate early DFS events (0 ~ 2 years) (TG/TC p = 0.021, TG/HDL p = 0.046, TG/LDL p < 0.001), and the TG/LDL ratio demonstrated the best predictive efficacy (TG/TC vs. TG/HDL vs. TG/LDL, 1-year AUC: 0.724 vs. 0.676 vs. 0.846, 2-year AUC: 0.653 vs. 0.638 vs. 0.708). CONCLUSION: Baseline serum TG/TC, TG/HDL and TG/LDL ratios were independent prognostic factors in patients with LABC undergoing neoadjuvant therapy. However, their utility in predicting the early DFS events warrants further investigation. CLINICAL TRIAL REGISTRATION: NCT05621564.

8.
Molecules ; 29(12)2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38930832

RESUMEN

In this research, with an aim to develop novel pyrazole oxime ether derivatives possessing potential biological activity, thirty-two pyrazole oxime ethers, including a substituted pyridine ring, have been synthesized and structurally identified through 1H NMR, 13C NMR, and HRMS. Bioassay data indicated that most of these compounds owned strong insecticidal properties against Mythimna separata, Tetranychus cinnabarinus, Plutella xylostella, and Aphis medicaginis at a dosage of 500 µg/mL, and some title compounds were active towards Nilaparvata lugens at 500 µg/mL. Furthermore, some of the designed compounds had potent insecticidal effects against M. separata, T. cinnabarinus, or A. medicaginis at 100 µg/mL, with the mortalities of compounds 8a, 8c, 8d, 8e, 8f, 8g, 8o, 8s, 8v, 8x, and 8z against A. medicaginis, in particular, all reaching 100%. Even when the dosage was lowered to 20 µg/mL, compound 8s also expressed 50% insecticidal activity against M. separata, and compounds 8a, 8e, 8f, 8o, 8v, and 8x displayed more than 60% inhibition rates against A. medicaginis. The current results provided a significant basis for the rational design of biologically active pyrazole oxime ethers in future.


Asunto(s)
Diseño de Fármacos , Insecticidas , Oximas , Pirazoles , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Oximas/química , Oximas/farmacología , Oximas/síntesis química , Insecticidas/química , Insecticidas/síntesis química , Insecticidas/farmacología , Animales , Relación Estructura-Actividad , Éteres/química , Estructura Molecular , Piridinas/química , Piridinas/farmacología , Piridinas/síntesis química , Mariposas Nocturnas/efectos de los fármacos
9.
Front Public Health ; 12: 1401044, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38932768

RESUMEN

Objective: To investigate the status quo of empathic fatigue, professional identity, and sleep quality of nursing staff in nursing institutions. To analyze the correlation between empathic fatigue, professional identity and sleep quality of nursing staff. Methods: This is a cross-sectional study. The method of convenient sampling was used to select 224 nursing workers from the older adult's institutions in the Panjin area as the investigation objects. The nurses' general data questionnaire, the Chinese version of the compassion fatigue short scale, the nurses' professional identity Scale, and the Pittsburgh Sleep Quality Index were used as evaluation tools. SPSS26.0 statistical software was used to sort out and analyze the data. Results: There was a positive correlation between empathic fatigue and sleep quality; there was a negative correlation between empathy fatigue and professional identity. Occupational identity and sleep quality were negatively correlated. Conclusion: There is a correlation between empathic fatigue, professional identity, and sleep quality of nursing workers. Empathy fatigue is positively correlated with sleep quality. Empathy fatigue was negatively correlated with professional identity. Occupational identity was negatively correlated with sleep quality. To provide a theoretical basis for the management of older adult's nursing staff and the formulation of corresponding management systems and policies, promote the mental health of older adult's nursing staff, improve sleep quality, and provide a theoretical basis and reference for future intervention research.


Asunto(s)
Desgaste por Empatía , Calidad del Sueño , Humanos , Estudios Transversales , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Desgaste por Empatía/psicología , China , Empatía , Personal de Enfermería/psicología , Personal de Enfermería en Hospital/psicología , Personal de Enfermería en Hospital/estadística & datos numéricos
10.
Am J Clin Nutr ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38942116

RESUMEN

BACKGROUND: Although high ultraprocessed food (UPF) consumption has been linked with increased mortality risk in the general population, whether UPFs harm participants with a history of cancer remains unclear. OBJECTIVES: This study aimed to evaluate the association of UPF consumption with mortality among participants with a history of cancer. METHODS: Prospective cohort analysis was conducted on 13,640 participants with a history of cancer from the UK Biobank. UPFs were defined by the Nova classification. UPF consumption was calculated as the weight proportion of UPFs in the total food consumption. Cox proportional hazard models were used to assess the association between UPF consumption and mortality among participants with a history of cancer. RESULTS: The median UPF consumption was 29.25% (interquartile range [IQR]: 19.46%-40.62%) for males and 25.81% (IQR: 16.61%-36.35%) for females in the total diet among participants with a history of cancer. During a median follow-up of 10.77 years, 1611 deaths were documented. Multivariable-adjusted hazard ratios (95% confidence intervals) among participants in the highest quartile of UPF consumption relative to the lowest were 1.17 (1.02, 1.35) for all-cause mortality and 1.22 (1.03, 1.44) for cancer-related mortality. CONCLUSIONS: Higher UPF consumption after the diagnosis among participants with a history of cancer is associated with higher risk of mortality.

11.
EMBO Mol Med ; 16(7): 1675-1703, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38806641

RESUMEN

Profibrotic proximal tubules (PT) were identified as a unique phenotype of proximal tubule cells (PTCs) in renal fibrosis by single-cell RNA sequencing (scRNA-seq). Controlling the process of renal fibrosis requires understanding how to manage the S1 subset's branch to the S3 subset rather than to the profibrotic PT subset. Insulin-induced gene 1 (Insig1) is one of the branch-dependent genes involved in controlling this process, although its role in renal fibrosis is unknown. Here, we discovered that tubular Insig1 deficiency, rather than fibroblast Insig1 deficiency, plays a detrimental role in the pathogenesis of renal fibrosis in vivo and in vitro. Overexpression of Insig1 profoundly inhibited renal fibrosis. Mechanistically, Insig1 deletion in PTCs boosted SREBP1 nuclear localization, increasing Aldh1a1 transcriptional activity, causing excessive NAD+ consumption and ER enlargement, as well as accelerating renal fibrosis. We also identified nicardipine as a selective inhibitor of Aldh1a1, which could restore NAD+ and maintain ER homeostasis, as well as improve renal fibrosis. Together, our findings support tubular Insig1 as a new therapeutic target for chronic kidney disease (CKD).


Asunto(s)
Fibrosis , Proteínas de la Membrana , NAD , Animales , Ratones , NAD/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/metabolismo , Masculino , Humanos , Ratones Endogámicos C57BL , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/metabolismo , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética
12.
Prev Med ; 185: 108021, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821420

RESUMEN

OBJECTIVE: Lifestyle factors after cancer diagnosis could influence cancer survival. This study aimed to investigate the joint effects of smoking, physical activity, alcohol consumption, diet and sleep duration on all-cause, cancer and non-cancer mortality of cancer survivors in UK biobank. METHODS: The follow-up period concluded in December 2021, with post-diagnostic lifestyle factors assessed at baseline. A lifestyle score ranging from 0 to 5 was assigned based on adherence to the selected lifestyle factors. The study employed Cox regression models for hazard ratios (HRs) and Kaplan-Meier for survival rates, with stratified and sensitivity analyses to assess the robustness of our findings under various assumptions. RESULTS: During a median follow-up of 12.7 years, 5652 deaths were documented from 34,184 cancer survivors. Compared to scoring 0-1, the HRs (95% CIs) for all-cause mortality with lifestyle scores of 2, 3, 4, and 5 were 0.70 (95% CI: 0.64, 0.76), 0.57 (0.52, 0.62), 0.50 (0.45, 0.54) and 0.43 (0.38, 0.48), respectively. Specific cancer types, particularly digestive, breast, female reproductive, non-solid, and skin cancers, showed notable benefits from adherence to healthy lifestyle, with the HRs of 0.55 (0.39, 0.79), 0.54 (0.42, 0.70), 0.32 (0.19, 0.53), 0.58 (0.39, 0.86), and 0.36 (0.28, 0.46) for lifestyle score of 5, respectively. Stratified analyses indicated the association was particularly significant among those with normal/lower BMI and higher Townsend Deprivation Index (Pinteraction = 0.001 and < 0.001, respectively). CONCLUSIONS: Healthier lifestyles were significantly linked with reduced mortality among cancer survivors. These findings highlight the need for adherence to healthy lifestyle habits to improve survival.

13.
Org Lett ; 26(22): 4779-4783, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38807481

RESUMEN

A new strategy to obtain ß,γ-unsaturated ketones via the cross-coupling of 1,3-butadiene, alkyl bromides, and arylboronic acids under 1 bar of CO with nickel as the catalyst has been developed. This newly developed four-component carbonylation procedure features advantages including using a cheap catalytic system, high step economy, mild reaction conditions, and excellent 1,4-regioselectivity, thereby providing a sustainable and alternative tool for ß,γ-unsaturated ketones production compared to the present tactics. To elucidate the application potential of this method, olefin synthons are derived from the representative coupling product.

14.
Mol Psychiatry ; 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704506

RESUMEN

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions. Different mutations on a single ASD gene contribute to heterogeneity of disease phenotypes, possibly due to functional diversity of generated isoforms. SHANK2, a causative gene in ASD, demonstrates this phenomenon, but there is a scarcity of tools for studying endogenous SHANK2 proteins in an isoform-specific manner. Here, we report a point mutation on SHANK2, which is found in a patient with autism, located on exon of the SHANK2B transcript variant (NM_133266.5), hereby SHANK2BY29X. This mutation results in an early stop codon and an aberrant splicing event that impacts SHANK2 transcript variants distinctly. Induced pluripotent stem cells (iPSCs) carrying this mutation, from the patient or isogenic editing, fail to differentiate into functional dopamine (DA) neurons, which can be rescued by genetic correction. Available SMART-Seq single-cell data from human midbrain reveals the abundance of SHANK2B transcript in the ALDH1A1 negative DA neurons. We then show that SHANK2BY29X mutation primarily affects SHANK2B expression and ALDH1A1 negative DA neurons in vitro during early neuronal developmental stage. Mice knocked in with the identical mutation exhibit autistic-like behavior, decreased occupancy of ALDH1A1 negative DA neurons and decreased dopamine release in ventral tegmental area (VTA). Our study provides novel insights on a SHANK2 mutation derived from autism patient and highlights SHANK2B significance in ALDH1A1 negative DA neuron.

15.
Small ; : e2402277, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773868

RESUMEN

It is still challenging to stabilize α-FAPbI3 perovskite for high performance optoelectrical devices. Herein, a novel strategy is proposed utilizing the synergetic electrostatic and steric effect to stabilize the α-FAPbI3 phase and suppress the ion migration. Dimethylamine (DMA+) cations are chosen as the dopant to fabricate FA0.96DMA0.04PbI3 single crystals (SCs). DFT calculations reveal that DMA+ cations can improve the stability of α-FAPbI3 phase in both thermodynamics (lower Gibbs free energy) and kinetics (higher defect formation and migration energy). The resulting SCs exhibit an environmental stability over 100 days and an extraordinary low dark current drift of 3.7 × 10-7 nA cm-1 s-1 V-1, comparable to 2D perovskite SCs. The X-ray detectors have also achieved the-state-of-the-art performance in X-ray detection and imaging. This work demonstrates the significance of electrostatic and steric effects in improving the phase and operational stability of perovskites.

16.
Molecules ; 29(10)2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38792046

RESUMEN

In response to the need for improvement in the utilization of ammonium-rich solutions after the electrochemical reduction of nitrate (NO3--RR), this study combined phosphorus-containing wastewater and adopted the electrochemical precipitation method for the preparation of struvite (MAP) to simultaneously recover nitrogen and phosphorus resources. At a current density of 5 mA·cm-2 and an initial solution pH of 7.0, the recovery efficiencies for nitrogen and phosphorus can reach 47.15% and 88.66%, respectively. Under various experimental conditions, the generated struvite (MgNH4PO4·6H2O) exhibits a typical long prismatic structure. In solutions containing nitrate and nitrite, the coexisting ions have no significant effect on the final product, struvite. Finally, the characterization of the precipitate product by X-ray diffraction (XRD) revealed that its main component is struvite, with a high purity reaching 93.24%. Overall, this system can effectively recover ammonium nitrogen from the NO3--RR solution system after nitrate reduction, with certain application prospects for the recovery of ammonium nitrogen and phosphate.

17.
Cell Rep ; 43(4): 114032, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38568805

RESUMEN

N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.


Asunto(s)
Desmetilasa de ARN, Homólogo 5 de AlkB , Carcinogénesis , Retroalimentación Fisiológica , Proteínas Supresoras de Tumor , Proteínas Supresoras de Tumor/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Retroalimentación Fisiológica/fisiología , Estabilidad Proteica , Fosforilación/genética , Glioblastoma/enzimología , Glioblastoma/fisiopatología , Humanos , Animales , Ratones , Línea Celular Tumoral , Adenosina/análogos & derivados , Adenosina/metabolismo , Recuento de Células , Proteolisis , Carcinogénesis/genética , Carcinogénesis/patología
18.
Front Immunol ; 15: 1357638, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38576608

RESUMEN

Objectives: With the increasing number of people worldwide infected with SARS-CoV-2, the likelihood of co-infection and/or comorbidities is rising. The impact of these co-infections on the patient's immune system remains unclear. This study aims to investigate the immunological characteristics of secondary infections in hospitalized COVID-19 patients, and preliminarily predict potential therapeutic effects of traditional Chinese medicine and their derivatives for the treatment of co-infections. Methods: In this retrospective cohort study, we included 131 hospitalized patients with laboratory-confirmed COVID-19, of whom there were 64 mild and 67 severe cases. We analyzed clinical characteristics and immunologic data, including circulating immune cell numbers, levels of inflammatory factors and viral load, comparing COVID-19 patients with and without co-infection. Results: Among 131 hospitalized COVID-19 patients, 41 (31.3%) were co-infection positive, with 33 (80.5%) having severe disease and 14 (34.1%) of them resulting in fatalities. Co-infected patients exhibited significantly higher severity and mortality rates compared to non-co-infected counterparts. Co-infected patients had significantly lower absolute counts of lymphocytes, total T lymphocytes, CD4+ T cells, CD8+ T cells and B lymphocytes, while levels of hs-CRP, PCT and IL-6 were significantly elevated compared to non-co-infected patients. Additionally, the viral load of co-infected patients was significantly higher than non-co-infected patients. Conclusion: Co-infection emerges as a dangerous factor for COVID-19 patients, elevating the risk of severe pneumonia and mortality. Co-infection suppresses the host's immune response by reducing the number of lymphocytes and increasing inflammation, thereby diminishing the antiviral and anti-infective effects of the immune system, which promotes the severity of the disease. Therefore, it is crucial to implement infection prevention measures to minimize the spread of co-infections among COVID-19 hospitalized patients. Additionally, changes in these biomarkers provide a theoretical basis for the effective treatment of co-infections with traditional Chinese medicine.


Asunto(s)
COVID-19 , Coinfección , Humanos , Coinfección/epidemiología , SARS-CoV-2 , Linfocitos T CD8-positivos , Estudios Retrospectivos , Medicina Tradicional China
19.
J Clin Med ; 13(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38610617

RESUMEN

Background: Recently, the classification of HER2 status evolves from binary to ternary, and HER2-low expression may exhibit prognostic significance. We aimed to investigate whether HER2-low tumor is distinct from HER2-zero or HER2-positive tumors, and then to develop a modified staging system (mNeo-Bioscore) that incorporates HER2-low status into Neo-Bioscore. Patients and Methods: This cohort study was conducted using data from the prospective database on breast cancer patients between January 2014 and February 2019. Results: Among 259 patients enrolled in the study, the HER2-low tumor exhibited significantly lower histological grade, pathological staging and Ki-67 level than the other two groups. HER2-low patients and HER2-positive patients receiving concurrent HER2-directed therapy may have similar LRFS (p = 0.531) and OS (p = 0.853), while HER2-zero peers may have significantly worse LRFS (p = 0.006) and OS (p = 0.017). In particular, a similar trend was also found in the patients without pathological complete response after surgery. Incorporation of HER2-low status made improvement in fit: 5-year OS rate estimates ranged from 33.33% to 100% for mNeo-Bioscore vs 61.36% to 100% for Neo-Bioscore. Conclusions: This study demonstrated that HER2-low tumor may exhibit prognostic significance. The innovative mNeo-Bioscore, based on a new classification of HER2 status, may serve as a prognostic staging system superior to Neo-Bioscore.

20.
Med Sci Monit ; 30: e942814, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38571286

RESUMEN

BACKGROUND The Chengdu pediatric emergency triage criteria were developed at our hospital and consist of 4 triage levels: immediate treatment (level 1), treatment within 10 min (level 2), treatment within 30 min (level 3), and treatment within 240 min (level 4). This study aimed to evaluate outcomes from the levels 1 to 4 of this triage criteria. MATERIAL AND METHODS A self-designed survey form was used to collect pediatric Emergency Department (ED) patients' general data, including age, sex, and chief concern, and clinical data, including triage level, whether the patient had died, and whether the patient was admitted to our hospital. A total of 198,628 patient records that were triaged during January to May 2022 using Chengdu pediatric emergency triage criteria were included in this retrospective study. The numbers of patients triaged to levels 1, 2, 3, and 4 were 128, 1164, 14,560, and 182,776, respectively. RESULTS Statistically significant differences were found in waiting time for treatment, hospital admission rates, admission conversion rates, and case mix index at admission under different triage levels. The higher the triage priority level, the shorter the waiting time for ED treatment, higher the hospital admission and admission conversion rates, and higher case mix index value. CONCLUSIONS The Chengdu pediatric emergency triage criteria developed and applied within our hospital appears to be characterized by good clinical validity. Equipped with this triage criteria, triage nurses are more capable of determining the severity and emergency of the pediatric ED patients' health conditions and effectively triaging the patients.


Asunto(s)
Hospitalización , Triaje , Humanos , Niño , Estudios Retrospectivos , Triaje/métodos , Servicio de Urgencia en Hospital , Hospitales
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