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1.
Eur J Med Res ; 29(1): 420, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143607

RESUMEN

BACKGROUND: It is well-established that thrombus aspiration during primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) indicates a higher thrombus burden and necessitates more intensive antithrombotic therapy. The bidirectional association between adverse events in AMI patients and platelet reactivity is typically observed during dual antiplatelet therapy (DAPT). OBJECTIVE: To investigate platelet reactivity after DAPT in AMI patients with thrombus aspiration performed during PCI. METHODS: In this retrospective study, we examined 269 consecutive AMI patients who underwent PCI and recorded their demographic, clinical and laboratory data. The platelet reactivity was measured with thromboelastogram (TEM). RESULTS: Ultimately, 208 patients were included in this study and divided into a Thrombus Aspiration group (N = 97) and a PCI Alone group (N = 111) based on whether thrombus aspiration was performed or not. The adenosine diphosphate (ADP)-induced platelet inhibition rate in the Thrombus Aspiration group was higher than that in the PCI Alone group (P < 0.001). Furthermore, multivariate linear regression analysis revealed that the ADP-induced platelet inhibition rate was independently associated with leukocyte count, thrombus aspiration and the combination of aspirin and ticagrelor as DAPT after adjusting for potential covariates in all AMI patients. CONCLUSION: In conclusion, clinicians should exercise heightened attention towards the bleeding risk among patients undergoing PCI concomitant with Thrombus Aspiration postoperatively.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria , Humanos , Masculino , Femenino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Inhibidores de Agregación Plaquetaria/efectos adversos , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Anciano , Intervención Coronaria Percutánea/métodos , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Terapia Antiplaquetaria Doble/métodos , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Trombosis/etiología , Trombosis/prevención & control , Plaquetas/efectos de los fármacos , Trombectomía/métodos
2.
Adv Mater ; : e2406636, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148152

RESUMEN

Bionic electrical stimulation (Bio-ES) aims to achieve personalized therapy and proprioceptive adaptation by mimicking natural neural signatures of the body, while current Bio-ES devices are reliant on complex sensing and computational simulation systems, thus often limited by the low-fidelity of simulated electrical signals, and failure of interface information interaction due to the mechanical mismatch between soft tissues and rigid electrodes. Here, the study presents a flexible and ultrathin self-sustainable bioelectronic patch (Bio-patch), which can self-adhere to the lesion area of organs and generate bionic electrical signals synchronized vagal nerve envelope in situ to implement Bio-ES. It allows adaptive adjustment of intensity, frequency, and waveform of the Bio-ES to fully meet personalized needs of tissue regeneration based on real-time feedback from the vagal neural controlled organs. With this foundation, the Bio-patch can effectively intervene with excessive fibrosis and microvascular stasis during the natural healing process by regulating the polarization time of macrophages, promoting the reconstruction of the tissue-engineered structure, and accelerating the repair of damaged liver and kidney. This work develops a practical approach to realize biomimetic electronic modulation of the growth and development of soft organs only using a multifunctional Bio-patch, which establishes a new paradigm for precise bioelectronic medicine.

3.
J Agric Food Chem ; 72(31): 17633-17648, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39051975

RESUMEN

Dendrobium officinale polysaccharide (DP) was prepared with lactic acid bacterium fermentation to overcome the large molecular weight and complex structure of traditional DP for improving its functional activity and application range in this work. The structure was analyzed, and then the functional activity was evaluated using a mouse model of alcoholic liver damage. The monosaccharide compositions were composed of four monosaccharides: arabinose (0.13%), galactose (0.50%), glucose (24.38%), and mannose (74.98%) with a molecular weight of 2.13 kDa. The connection types of glycosidic bonds in fermented D. officinale (KFDP) were →4)-ß-D-Manp(1→, →4)-ß-Glcp(1→, ß-D-Manp(1→, and ß-D-Glcp(1→. KFDP exhibited an excellent protective effect on alcoholic-induced liver damage at a dose of 80 mg/kg compared with polysaccharide separated and purified from D. officinale without fermentation (KDP), which increased the activity of GSH, GSH-Px, and GR and decreased the content of MDA, AST, T-AOC, and ALT, as well as regulated the level of IL-6, TNF-α, and IL-1ß to maintain the normal functional structure of hepatocytes and retard the apoptosis rate of hepatocytes. The results proved that fermentation degradation is beneficial to improving the biological activity of polysaccharides. The potential mechanism of KFDP in protecting alcoholic liver damage was inhibiting the expression of miRNA-150-5p and targeting to promote the expression of Pik3r1. This study provides an important basis for the development of functional foods.


Asunto(s)
Dendrobium , Fermentación , Hepatopatías Alcohólicas , Hígado , Polisacáridos , Animales , Ratones , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/administración & dosificación , Dendrobium/química , Masculino , Hepatopatías Alcohólicas/prevención & control , Hepatopatías Alcohólicas/metabolismo , Hepatopatías Alcohólicas/tratamiento farmacológico , Humanos , Hígado/metabolismo , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Sustancias Protectoras/administración & dosificación , Lactobacillales/metabolismo , Lactobacillales/genética , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación
4.
Aging Clin Exp Res ; 36(1): 149, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023685

RESUMEN

BACKGROUND: Hypotension, characterized by abnormally low blood pressure, is a frequently observed adverse event in sedated gastrointestinal endoscopy procedures. Although the examination time is typically short, hypotension during and after gastroscopy procedures is frequently overlooked or remains undetected. This study aimed to construct a risk nomogram for post-anesthesia care unit (PACU) hypotension in elderly patients undergoing sedated gastrointestinal endoscopy. METHODS: This study involved 2919 elderly patients who underwent sedated gastrointestinal endoscopy. A preoperative questionnaire was used to collect data on patient characteristics; intraoperative medication use and adverse events were also recorded. The primary objective of the study was to evaluate the risk of PACU hypotension in these patients. To achieve this, the least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection, involving cyclic coordinate descent with tenfold cross-validation. Subsequently, multivariable logistic regression analysis was applied to build a predictive model using the selected predictors from the LASSO regression. A nomogram was visually developed based on these variables. To validate the model, a calibration plot, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used. Additionally, external validation was conducted to further assess the model's performance. RESULTS: The LASSO regression analysis identified predictors associated with an increased risk of adverse events during surgery: age, duration of preoperative water abstinence, intraoperative mean arterial pressure (MAP) <65 mmHg, decreased systolic blood pressure (SBP), and use of norepinephrine (NE). The constructed model based on these predictors demonstrated moderate predictive ability, with an area under the ROC curve of 0.710 in the training set and 0.778 in the validation set. The DCA indicated that the nomogram had clinical applicability when the risk threshold ranged between 20 and 82%, which was subsequently confirmed in the external validation with a range of 18-92%. CONCLUSION: Incorporating factors such as age, duration of preoperative water abstinence, intraoperative MAP <65 mmHg, decreased SBP, and use of NE in the risk nomogram increased its usefulness for predicting PACU hypotension risk in elderly patient undergoing sedated gastrointestinal endoscopy.


Asunto(s)
Endoscopía Gastrointestinal , Hipotensión , Humanos , Hipotensión/diagnóstico , Anciano , Femenino , Masculino , Endoscopía Gastrointestinal/métodos , Endoscopía Gastrointestinal/efectos adversos , Anciano de 80 o más Años , Nomogramas , Periodo de Recuperación de la Anestesia , Curva ROC
5.
Curr Microbiol ; 81(8): 228, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38890167

RESUMEN

Soil nutrient deficiency has become a key factor limiting crop growth. Plant growth-promoting rhizobacteria (PGPR) are vital in resisting abiotic stress. In this study, we investigated the effects of inoculation with Bacillus amyloliquefaciens JB20221020 on the physiology, biochemistry, rhizosphere microorganisms, and metabolism of lettuce under nutrient stress. Pot experiments showed that inoculation with B. amyloliquefaciens JB20221020 significantly promoted lettuce growth under nutrient deficiency. At the same time, the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase and the content of proline increased, and the content of Malondialdehyde decreased in the lettuce inoculated with B. amyloliquefaciens JB20221020. Inoculation with B. amyloliquefaciens JB20221020 altered the microbial community of the rhizosphere and increased the relative abundances of Myxococcales, Deltaproteobacteria, Proteobacteria, Devosia, and Verrucomicrobia. Inoculation also altered the rhizosphere metabolism under nutrient deficiency. The folate metabolism pathway was significantly enriched in the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. This study explored the interaction between plants and microorganisms under nutrient deficiency, further explained the critical role of rhizosphere microorganisms in the process of plant nutrient stress, and provided a theoretical basis for the use of microorganisms to improve plant resistance.


Asunto(s)
Bacillus amyloliquefaciens , Lactuca , Rizosfera , Microbiología del Suelo , Estrés Fisiológico , Bacillus amyloliquefaciens/metabolismo , Bacillus amyloliquefaciens/fisiología , Lactuca/microbiología , Lactuca/crecimiento & desarrollo , Nutrientes/metabolismo , Microbiota , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/genética , Suelo/química
6.
Clin Med Insights Case Rep ; 17: 11795476241262213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38895742

RESUMEN

Background: Cerebral infarct associated with varicella-zoster virus (VZV) has been reported in the literature, while isolated central dizziness due to lateral medullary infarct (LMI) following VZV infection is rarely reported. Case report: We report the case of a 65-year-old man who presented to the neurology department because of herpes zoster on the right trigeminal nerve distribution. At 12 hours after admission, he developed transient vertigo along with nausea and unsteady walking and left-sided spontaneous horizontal nystagmus, gaze-evoked nystagmus, and upbeat nystagmus. The other usual signs of LMI including Horner syndrome, dysarthria, swallowing difficulty, and hemibody sensory change were absent. Video head impulse indicated decreased head impulse gain of the vestibulo-ocular reflex for the bilateral horizontal, anterior, and posterior semicircular canals with abnormal saccade waves. Suppression head impulse paradigm showed few downward saccades reflecting anti-compensatory saccades after the end of the head impulse back to the head-fixed target and decreased vestibulo-ocular reflex gain values of bilateral semicircular canals. Brain magnetic resonance imaging (MRI) showed a small infarct in the far dorsolateral portion of the left rostral medulla. The cerebrospinal fluid was positive for VZV DNA. Conclusions: In patients with VZV infection who develop dizziness, the possibility of cerebral infarct should be considered. Patients with facial herpes zoster and neurological symptoms always be screened for stroke using MRI and lumbar puncture should be performed and acyclovir administered empirically.

7.
Discov Oncol ; 15(1): 221, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861194

RESUMEN

Acute myeloid leukemia (AML) remains challenging due to chemotherapeutic drug-resistance (CDR). Aberrant expression B7 family proteins are involved in tumors evasion. We wonder whether B7 family protein alteration in AML CDR further supports tumor escape. Here, we establish AML cytarabine-resistant cell line U937/Ara-C and report on the expression MHC molecule and B7 family member. HLA-ABC was highly expressed similarly on both cell lines. MIC (MHC class I chain related) A/B and B7-H6 was moderately expressed on the surface of U937 and decreased dramatically by U937/Ara-C. In contrast, enhanced expression of B7-H1 and B7-H7 by U937/Ara-C was observed. HLA-DR and other B7 family members including CD80, CD86, B7-DC, B7-H2, B7-H3, B7-H4, and B7-H5 were not detected by both cell lines. Compared co-cultured with U937, peripheral blood mononuclear cells showed a decreased cytotoxicity when incubated with U937/Ara-C, as indicated by decreased levels of granzyme B and perforin production, accompanied with less TNF-α and lactate dehydrogenase secretion. In conclusion, AML CDR further evades the anti-tumor immune response which may through MHC molecule and B7 family members.

8.
Mol Biotechnol ; 2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38824489

RESUMEN

To investigate the biological effects of the ABA receptor pyrabactin resistance 1-like (PYR1-like) in Malus sieversii seeds, the proteins interacting with MsPYR1-like were screened by the membrane yeast two-hybrid library based on the split-ubiquitin system, and to construct the bait vector pBT3-SUC-PYR1 for Malus sieversii cDNA library, which had no self-activating effect on the yeast cells of the pPR3-N membrane yeast two-hybrid library. The library titer assay showed that it could meet the requirements for membrane yeast two-hybrid library screening. After sequencing, GenBank database blast, and yeast rotary validation, 28 candidate proteins interacting with MsPYR1-like were obtained, including ribosomal proteins, late embryogenesis abundant proteins, F-actin-capping proteins, phytochrome-interacting proteins, low-temperature-inducible 65 kDa protein-like, senescence-associated, PP2C and SnRK2 family members, and unknown proteins. Gene ontology analysis of the interaction proteins was related to plant hormone response and negative regulation of seed germination, overexpression of MsPYR1-like in Arabidopsis negatively regulates seed germination, and the study of the biological roles of MsPYR1-like interacting proteins lays the foundation for revealing the lifting of seed dormancy in Malus sieversii.

9.
Ann Clin Transl Neurol ; 11(8): 2040-2048, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38858521

RESUMEN

OBJECTIVE: Endovascular thrombectomy (EVT) in patients with large infarct volume remains controversial. The aim of this study is to compare clinical outcomes between EVT and medical management in acute large vessel occlusion with infarct volumes larger than 70 mL on diffusion-weighted magnetic resonance imaging (DWI). METHODS: A prospective observational cohort study was conducted, including patients with anterior cerebral circulation occlusion due to ischemic stroke with infarct volumes larger than 70 mL within 24 h of onset between July 2018 and June 2023. Eligible patients were divided into two groups: the EVT group and the medical management (non-EVT) group. The main outcomes were functional independence and mortality at 90 days. To assess clinical endpoints, we selected variables including age, NIHSS score, infarct volume, and occlusion location for 1:1 propensity score (PS) matching and PS adjustment using inverse probability of treatment weighting (IPTW). RESULTS: Among the 131 identified patients (mean [SD] age, 69.9 [13.7] years; 58 female), the median infarct volume was 123.6 mL. Of these patients, 75 (57.3%) underwent EVT. After PS adjustment, EVT was not associated with functional independence (10.9% vs. 10.9%; p = 1.000) or mortality (43.5% vs. 47.8%; p = 0.675). Additionally, after PS adjustment using IPTW, EVT was also not associated with a functional independence (15.8% vs. 13.7%; p = 0.767) or mortality (46.8% vs. 44.0%; p = 0.762). CONCLUSION: This study provides real-world evidence regarding infarct volumes larger than 70 mL, indicating that EVT does not provide benefits compared to medical management alone when considering age, NIHSS score, infarct volume, and occlusion location.


Asunto(s)
Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Trombectomía , Humanos , Femenino , Masculino , Trombectomía/métodos , Anciano , Persona de Mediana Edad , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Anciano de 80 o más Años , Estudios Prospectivos , Evaluación de Resultado en la Atención de Salud , Resultado del Tratamiento
10.
Fitoterapia ; 177: 106052, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38848978

RESUMEN

Hypoxia-inducing factor-1α (HIF-1α) is overexpressed in variety of tumor patients and plays an important role in the regulation of hypoxia response in tumor cells. Therefore, its inhibitors have become one of the targets for the treatment of a variety of cancers. Two series of panaxadiol (PD) ester derivatives containing pyrazole (18a-j) and pyrrole (19a-n) moiety were synthesized and their HIF-1α inhibitory activities were evaluated. Among all the target compouds, compounds 18c, 19d, and 19n (IC50 = 8.70-10.44 µM) showed better HIF-1α inhibitory activity than PD (IC50 = 13.35 µM). None of these compounds showed cytotoxicity above 100 µM and inhibited HIF-1α transcription in a dose-dependent manner. These compounds showed good antitumor activity and provide lead compounds for further design and activity study of PD ester derivatives.


Asunto(s)
Ésteres , Ginsenósidos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Pirazoles , Pirroles , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Pirroles/farmacología , Pirroles/química , Pirroles/síntesis química , Estructura Molecular , Línea Celular Tumoral , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Ésteres/química , Ésteres/farmacología , Ésteres/síntesis química , Ginsenósidos/farmacología , Ginsenósidos/química , Ginsenósidos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad
12.
Front Nutr ; 11: 1379096, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38765818

RESUMEN

Background: The yearly escalation in hypertension prevalence signifies a noteworthy public health challenge. Adhering to a nutritious diet is crucial for enhancing the quality of life among individuals managing hypertension. However, the relationship between vitamin C and hypertension, as well as homocysteine, remains unclear. Objective: The primary aim of this investigation was to scrutinize the potential mediating role of Vitamin C in the association between homocysteine levels and blood pressure, utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES) database. Methods: A total of 7,327 participants from the NHANES 2003-2006 were enrolled in this cross-sectional survey. The main information was obtained using homocysteine, Vitamin C, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Correlation analysis was used to assess the correlation between homocysteine, SBP, DBP and vitamin C. Linear regression analysis was utilized to determine the ß value (ß) along with its 95% confidence intervals (CIs). Mediation analysis was performed to investigate whether the relationship between homocysteine and blood pressure was mediated by Vitamin C, and to quantify the extent to which Vitamin C contributed to this association. Results: The results manifested that the homocysteine was positively associated with SBP (r = 0.24, p < 0.001) and DBP (r = 0.03, p < 0.05), while negatively correlated with Vitamin C (r = -0.008, p < 0.001). Vitamin C was found to be negatively associated with SBP (r = -0.03, p < 0.05) and DBP (r = 0.11, p < 0.001). Mediation effect analysis revealed that a partial mediation (indirect effect: 0.0247[0.0108-0.0455], p < 0.001) role accounting for 11.5% of total effect, among homocysteine and SBP. However, the mediating effect of Vitamin C between homocysteine and DBP was not statistically significant. Conclusion: Hypertension patients should pay attention to homocysteine and Vitamin C level. What is more, hypertension patients ought to formulate interventions for Vitamin C supplementation as well as homocysteine reduce strategies to lower blood pressure.

13.
J Funct Biomater ; 15(5)2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38786638

RESUMEN

Nano-adjuvant vaccines could induce immune responses and enhance immunogenicity. However, the application and manufacturing of nano-adjuvant is hampered by its challenging scale-up, poor reproducibility, and low security. Therefore, the present study aimed to optimize the preparation nanoparticles (NPs) using FDA-approved biopolymer materials poly(lactic acid) (PLA) and cationic lipid didodecyl-dimethyl-ammonium bromide (DDAB), develop the scale-up process, and evaluate the stability and biosafety of it. The optimum preparation conditions of DDAB/PLA NPs on a small scale were as follows: DDAB amount of 30 mg, aqueous phase volume of 90 mL, stirring rate at 550 rpm, and solidifying time of 12 h. Under the optimum conditions, the size of the NPs was about 170 nm. In scale-up preparation experiments, the vacuum rotary evaporation of 6 h and the Tangential flow ultrafiltration (TFU) method were the optimum conditions. The results suggested that DDAB/PLA NPs exhibited a uniform particle size distribution, with an average size of 150.3 ± 10.4 nm and a narrow polydispersity index (PDI) of 0.090 ± 0.13, coupled with a high antigen loading capacity of 85.4 ± 4.0%. In addition, the DDAB/PLA NPs can be stored stably for 30 days and do not have side effects caused by residual solvents. For biosafety, the acute toxicity experiments showed good tolerance of the vaccine formulation even at a high adjuvant dose. The local irritation experiment demonstrated the reversibility of muscular irritation, and the repeated toxicity experiment revealed no significant necrosis or severe lesions in mice injected with the high-dose vaccine formulation. Overall, the DDAB/PLA NPs exhibit potential for clinical translation as a safe candidate vaccine adjuvant.

14.
Appl Microbiol Biotechnol ; 108(1): 313, 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38683244

RESUMEN

To avoid the unreasonable use of chemical fertilizer, an environmentally friendly means of improving soil fertility is required. This study explored the role of the plant growth-promoting rhizosphere bacteria (PGPR) strain Bacillus velezensis SAAS-63 in improving nutrient stress in lettuce. Compared with no inoculation, B. velezensis SAAS-63 inoculants exhibited significantly increased fresh weight, root length, and shoot height under nutrient deficiency, as well as improved antioxidant activities and proline contents. The exogenous addition of B. velezensis SAAS-63 also significantly increased the accumulation of macroelements and micronutrients in lettuce. To elucidate the resistance mechanisms induced by B. velezensis SAAS-63 under nutrient stress, high-throughput sequencing and multi-omics analysis were performed. Inoculation with B. velezensis SAAS-63 altered the microbial community of the rhizosphere and increased the relative abundances of Streptomyces, Actinoallomurus, Verrucomicrobia, and Chloroflexi. It is worth noting that the inoculant SAAS-63 can affect plant rhizosphere metabolism. The inoculant changed the metabolic flow of phenylpropanoid metabolic pathway under nutrient deficiency and promoted phenylalanine to participate more in the synthesis of lignin precursors and coumarin substances by inhibiting the synthesis of flavone and isoflavone, thus improving plant resistance. This study showed that the addition of inoculant SAAS-63 could help plants recruit microorganisms to decompose and utilize trehalose and re-established the carbon metabolism of the plant rhizosphere. Additionally, microbes were found to be closely related to the accumulation of metabolites based on correlation analysis. The results indicated that the addition of PGPRs has an important role in regulating soil rhizosphere microbes and metabolism, providing valuable information for understanding how PGPRs affect complex biological processes and enhance plant adaptation to nutrient deficiency. KEY POINTS: • Inoculation with SAAS-63 significantly promoted plant growth under nutrient-deficient conditions • Inoculation with SAAS-63 affected rhizosphere microbial diversity and community structure • Inoculation with SAAS-63 affected plant rhizosphere metabolism and induced plants to synthesize substances that resist stress.


Asunto(s)
Bacillus , Lactuca , Nutrientes , Rizosfera , Microbiología del Suelo , Estrés Fisiológico , Bacillus/metabolismo , Bacillus/genética , Lactuca/microbiología , Lactuca/crecimiento & desarrollo , Nutrientes/metabolismo , Raíces de Plantas/microbiología , Microbiota , Multiómica
15.
Cancer Lett ; 590: 216868, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38593920

RESUMEN

While previous studies have indicated the involvement of Isthmin 1 (ISM1), a secreted protein, in cancer development, the precise mechanisms have remained elusive. In this study, we unveiled that ISM1 is significantly overexpressed in both the blood and tissue samples of colorectal cancer (CRC) patients, correlating with their poor prognosis. Functional experiments demonstrated that enforced ISM1 expression significantly enhances CRC proliferation, migration, invasion and tumor growth. Notably, our investigation reveals an interaction of ISM1 with epidermal growth factor receptor (EGFR), a member of the receptor tyrosine kinase (RTK) family of CRC cells. The binding of ISM1 triggered EGFR activation and initiate downstream signaling pathways. Meanwhile, intracellular ISM1 interacted with Y-box binding protein 1 (YBX1), enhancing its transcriptional regulation on EGFR. Furthermore, our research uncovered the regulation of ISM1 expression by the hypoxia-inducible transcription factor HIF-1α in CRC cells. Mechanistically, we identified HIF-1α as a direct regulator of ISM1, binding to a hypoxia response element on its promoter. This novel mechanism illuminated potential therapeutic targets, offering insights into restraining HIF-1α/ISM1/EGFR-driven CRC progression and metastasis.


Asunto(s)
Proliferación Celular , Neoplasias Colorrectales , Progresión de la Enfermedad , Receptores ErbB , Regulación Neoplásica de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteína 1 de Unión a la Caja Y , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Proteína 1 de Unión a la Caja Y/metabolismo , Proteína 1 de Unión a la Caja Y/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Animales , Movimiento Celular , Línea Celular Tumoral , Ratones , Masculino , Transducción de Señal , Femenino , Ratones Desnudos , Células HCT116 , Pronóstico
16.
Am J Cancer Res ; 14(2): 744-761, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38455396

RESUMEN

Colorectal cancer (CRC) and gastric cancer (GC) rank the top five common and lethal cancers worldwide. Early detection can significantly reduce the mortality of CRC and GC. However, current clinical screening methods including invasive endoscopic techniques and noninvasive fecal occult blood test screening tests/fecal immunochemical test have shown low sensitivity or unsatisfactory patient's compliance. Aberrant DNA methylation occurs frequently in tumorigenesis and cell-free DNA (cfDNA) methylation has shown the potential in multi-cancer detection. Herein, we aimed to explore the value of cfDNA methylation in the gastrointestinal cancer detection and develop a noninvasive method for CRC and GC detection. We applied targeted methylation sequencing on a total of 407 plasma samples from patients diagnosed with CRC, GC, and noncancerous gastrointestinal benign diseases (Non-Ca). By analyzing the methylation profiles of 34 CRC, 62 GC and 107 Non-Ca plasma samples in the training set (n=203), we identified 40,110 gastrointestinal cancer-specific markers and 63 tissue of origin (TOO) prediction markers. A new integrated model composed of gastrointestinal cancer detection and TOO prediction for three types of classification of CRC, GC and Non-Ca patients was further developed through logistic regression algorithm and validated in an independent validation set (n=103). The model achieved overall sensitivities of 83% and 81.3% at specificities of 81.5% and 80% for identifying gastrointestinal cancers in the test set and validation set, respectively. The detection sensitivities for GC and CRC were respectively 81.4% and 83.3% in the cohort of the test and validation sets. Among these true positive cancer samples, further TOO prediction showed accuracies of 95.8% and 95.8% for GC patients and accuracies of 86.7% and 93.3% for CRC patients, in test set and validation set, respectively. Collectively, we have identified novel cfDNA methylation biomarkers for CRC and GC detection and shown the promising potential of cfDNA as a noninvasive gastrointestinal cancer detection tool.

17.
Diabetol Metab Syndr ; 16(1): 67, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38481310

RESUMEN

OBJECTIVE: Triglyceride glucose (TyG) index is considered as a new alternative marker of insulin resistance and a clinical predictor of type 2 diabetes mellitus (T2DM) combined with coronary artery disease. However, the prognostic value of TyG index on No-Reflow (NR) Phenomenon in T2DM patients with acute myocardial infarction (AMI) remains unclear. METHODS: In this retrospective study, 1683 patients with T2DM and AMI underwent primary percutaneous coronary intervention (PCI) were consecutively included between January 2014 and December 2019. The study population was divided into two groups as follows: Reflow (n = 1277) and No-reflow (n = 406) group. The TyG index was calculated as the ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2].Multivariable logistic regression models and receiver-operating characteristic curve analysis were conducted to predict the possible risk of no-reflow. Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were calculated to determine the ability of the TyG index to contribute to the baseline risk model. RESULTS: Multivariable logistic regression models revealed that the TyG index was positively associated with NR[OR,95%CI:5.03,(2.72,9.28),p<0.001] in patients with T2DM and AMI. The area under the curve (AUC) of the TyG index predicting the occurrence of NR was 0.645 (95% CI 0.615-0.673; p < 0.001)], with the cut-off value of 8.98. The addition of TyG index to a baseline risk model had an incremental effect on the predictive value for NR [net reclassification improvement (NRI): 0.077(0.043to 0.111), integrated discrimination improvement (IDI): 0.070 (0.031to 0.108), all p < 0.001]. CONCLUSIONS: High TyG index was associated with an increased risk of no-reflow after PCI in AMI patients with T2DM. The TyG index may be a valid predictor of NR phenomenon of patients with T2DM and AMI. Early recognition of NR is critical to improve outcomes with AMI and T2DM patients.

18.
Small ; 20(30): e2308715, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38412419

RESUMEN

Biomolecular piezoelectric materials show great potential in the field of wearable and implantable biomedical devices. Here, a self-assemble approach is developed to fabricating flexible ß-glycine piezoelectric nanofibers with interfacial polarization locked aligned crystal domains induced by Nb2CTx nanosheets. Acted as an effective nucleating agent, Nb2CTx nanosheets can induce glycine to crystallize from edges toward flat surfaces on its 2D crystal plane and form a distinctive eutectic structure within the nanoconfined space. The interfacial polarization locking formed between O atom on glycine and Nb atom on Nb2CTx is essential to align the ß-glycine crystal domains with (001) crystal plane intensity extremely improved. This ß-phase glycine/Nb2CTx nanofibers (Gly-Nb2C-NFs) exhibit fabulous mechanical flexibility with Young's modulus of 10 MPa, and an enhanced piezoelectric coefficient of 5.0 pC N-1 or piezoelectric voltage coefficient of 129 × 10-3Vm N-1. The interface polarization locking greatly improves the thermostability of ß-glycine before melting (≈210°C). A piezoelectric sensor based on this Gly-Nb2C-NFs is used for micro-vibration sensing in vivo in mice and exhibits excellent sensing ability. This strategy provides an effective approach for the regular crystallization modulation for glycine crystals, opening a new avenue toward the design of piezoelectric biomolecular materials induced by 2D materials.

19.
Cell Commun Signal ; 22(1): 132, 2024 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-38368403

RESUMEN

Abnormal inflammatory states in the brain are associated with a variety of brain diseases. The dynamic changes in the number and function of immune cells in cerebrospinal fluid (CSF) are advantageous for the early prediction and diagnosis of immune diseases affecting the brain. The aggregated factors and cells in inflamed CSF may represent candidate targets for therapy. The physiological barriers in the brain, such as the blood‒brain barrier (BBB), establish a stable environment for the distribution of resident immune cells. However, the underlying mechanism by which peripheral immune cells migrate into the brain and their role in maintaining immune homeostasis in CSF are still unclear. To advance our understanding of the causal link between brain diseases and immune cell status, we investigated the characteristics of immune cell changes in CSF and the molecular mechanisms involved in common brain diseases. Furthermore, we summarized the diagnostic and treatment methods for brain diseases in which immune cells and related cytokines in CSF are used as targets. Further investigations of the new immune cell subtypes and their contributions to the development of brain diseases are needed to improve diagnostic specificity and therapy.


Asunto(s)
Encefalopatías , Encéfalo , Humanos , Barrera Hematoencefálica/fisiología , Encefalopatías/diagnóstico , Encefalopatías/terapia , Transporte Biológico , Homeostasis
20.
Blood ; 143(11): 1045-1049, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38194678

RESUMEN

ABSTRACT: Current iron overload therapeutics have inherent drawbacks including perpetuated low hepcidin. Here, we unveiled that lactate, a potent hepcidin agonist, effectively reduced serum and hepatic iron levels in mouse models of iron overload with an improved erythropoiesis in ß-thalassemic mice.


Asunto(s)
Sobrecarga de Hierro , Talasemia beta , Ratones , Animales , Hepcidinas , Modelos Animales de Enfermedad , Ácido Láctico , Talasemia beta/tratamiento farmacológico , Sobrecarga de Hierro/tratamiento farmacológico
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