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BACKGROUND: Early gastric cancer (EGC) is a common malignant tumor of the digestive system, and its lymph node metastasis and survival prognosis have been concerning. By retrospectively analyzing the clinical data of EGC patients, we can better understand the status of lymph node metastasis and its impact on survival and prognosis. AIM: To evaluate the prognosis of EGC patients and the factors that affect lymph node metastasis. METHODS: The clinicopathological data of 1011 patients with EGC admitted to our hospital between January 2015 and December 2023 were collected in a retrospective cohort study. There were 561 males and 450 females. The mean age was 58 ± 11 years. The patient underwent radical gastrectomy. The status of lymph node metastasis in each group was determined according to the pathological examination results of surgical specimens. The outcomes were as follows: (1) Lymph node metastasis in EGC patients; (2) Analysis of influencing factors of lymph node metastasis in EGC; and (3) Analysis of prognostic factors in patients with EGC. Normally distributed measurement data are expressed as mean ± SD, and a t test was used for comparisons between groups. The data are expressed as absolute numbers or percentages, and the chi-square test was used for comparisons between groups. Rank data were compared using a nonparametric rank sum test. A log-rank test and a logistic regression model were used for univariate analysis. A logistic stepwise regression model and a Cox stepwise regression model were used for multivariate analysis. The Kaplan-Meier method was used to calculate the survival rate and construct survival curves. A log-rank test was used for survival analysis. RESULTS: Analysis of influencing factors of lymph node metastasis in EGC. The results of the multifactor analysis showed that tumor length and diameter, tumor site, tumor invasion depth, vascular thrombus, and tumor differentiation degree were independent influencing factors for lymph node metastasis in patients with EGC (odds ratios = 1.80, 1.49, 2.65, 5.76, and 0.60; 95%CI: 1.29-2.50, 1.11-2.00, 1.81-3.88, 3.87-8.59, and 0.48-0.76, respectively; P < 0.05). Analysis of prognostic factors in patients with EGC. All 1011 patients with EGC were followed up for 43 (0-13) months. The 3-year overall survival rate was 97.32%. Multivariate analysis revealed that age > 60 years and lymph node metastasis were independent risk factors for prognosis in patients with EGC (hazard ratio = 9.50, 2.20; 95%CI: 3.31-27.29, 1.00-4.87; P < 0.05). Further analysis revealed that the 3-year overall survival rates of gastric cancer patients aged > 60 years and ≤ 60 years were 99.37% and 94.66%, respectively, and the difference was statistically significant (P < 0.05). The 3-year overall survival rates of patients with and without lymph node metastasis were 95.42% and 97.92%, respectively, and the difference was statistically significant (P < 0.05). CONCLUSION: The lymph node metastasis rate of EGC patients was 23.64%. Tumor length, tumor site, tumor infiltration depth, vascular cancer thrombin, and tumor differentiation degree were found to be independent factors affecting lymph node metastasis in EGC patients. Age > 60 years and lymph node metastasis are independent risk factors for EGC prognosis.
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Abnormal melanogenesis can lead to hyperpigmentation. Tyrosinase (TYR), a key rate-limiting enzyme in melanin production, is an important therapeutic target for these disorders. We investigated the TYR inhibitory activity of hydrolysates extracted from the muscle tissue of Takifugu flavidus (TFMH). We used computer-aided virtual screening to identify a novel peptide that potently inhibited melanin synthesis, simulated its binding mode to TYR, and evaluated functional efficacy in vitro and in vivo. TFMH inhibited the diphenolase activities of mTYR, reducing TYR substrate binding activity and effectively inhibiting melanin synthesis. TFMH indirectly reduced cAMP response element-binding protein phosphorylation in vitro by downregulating melanocortin 1 receptor expression, thereby inhibiting expression of the microphthalmia-associated transcription factor, further decreasing TYR, tyrosinase related protein 1, and dopachrome tautomerase expression and ultimately impeding melanin synthesis. In zebrafish, TFMH significantly reduced black spot formation. TFMH (200 µg/mL) decreased zebrafish TYR activity by 43% and melanin content by 52%. Molecular dynamics simulations over 100 ns revealed that the FGFRSP (T-6) peptide stably binds mushroom TYR via hydrogen bonds and ionic interactions. T-6 (400 µmol/L) reduced melanin content in B16F10 melanoma cells by 71% and TYR activity by 79%. In zebrafish, T-6 (200 µmol/L) inhibited melanin production by 64%. TFMH and T-6 exhibit good potential for the development of natural skin-whitening cosmetic products.
Assuntos
Melaninas , Melanoma Experimental , Monofenol Mono-Oxigenase , Takifugu , Peixe-Zebra , Animais , Melaninas/biossíntese , Takifugu/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Camundongos , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Linhagem Celular Tumoral , Fator de Transcrição Associado à Microftalmia/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Oxirredutases Intramoleculares/metabolismo , Receptor Tipo 1 de Melanocortina/metabolismo , Simulação de Dinâmica Molecular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismoRESUMO
AIM: To assess the effect of intravenously injected superparamagnetic iron oxide nanoparticle (SPION)-labeled adipose-derived stem cells (ADSCs) under an external magnetic field on the efficacy of ADSC transplantation in rats with spinal cord injury (SCI). MATERIAL AND METHODS: ADSCs were isolated from rats, labeled with SPIONs, and divided into magnetic and non-magnetic groups. A rat model of SCI was established, and the SCI rats were randomly divided into magnetic, non-magnetic, and control groups, with ten rats in each group. Rats in the magnetic and non-magnetic groups were injected with SPION-labeled ADSCs via the tail vein. Simultaneously, a 300 mT neodymium iron boron magnet was placed externally at the SCI site of rats in the magnetic group. One and two weeks after successful modeling, SCI rats were scored for the degree of SCI (Basso, Beattie, and Bresnahan [BBB] method) and assessed for histopathology of the spinal cord (hematoxylin-eosin [HE] staining), the number of ADSCs at the SCI site (Prussian blue staining), and growth-associated protein-43 (GAP-43) expression in the spinal cord tissues. RESULTS: One and two weeks after modeling, the BBB scores were highest in the magnetic group, followed by the non-magnetic group, and lowest in the control group. HE staining showed that the histopathological manifestations of the spinal cord in the magnetic group were somewhat improved compared with those in the non-magnetic and control groups. Two weeks after modeling, Prussian blue staining revealed that ADSCs were significantly higher in the spinal cord tissue of the magnetic group than in the non-magnetic group. One and two weeks after modeling, western blotting elucidated that the magnetic group exhibited the highest GAP-43 expression. CONCLUSION: An external magnetic field at the SCI site in rats exerts a directional effect on SPION-labeled ADSCs, directing their migration and improving the efficacy of stem cell-targeted therapy for SCI.