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In clinical practice, the diagnosis of ulcerative colitis (UC) mainly relies on a comprehensive analysis of a series of signs and symptoms of patients. The current biomarkers for diagnosis of UC and prognostic prediction of anti-TNF-α therapy are inaccurate. The present study aimed to perform an integrative analysis of gene expression profiles in patients with UC. A total of seven datasets from the GEO database that met our strict inclusion criteria were included. After identifying differentially expressed genes (DEGs) between UC patients and healthy individuals, the diagnostic and prognostic utility of the DEGs were then analyzed via least absolute shrinkage and selection operator and support-vector machine recursive feature elimination. Subgroup analyses of the treated and untreated groups, as well as the treatment-response group and non-response group, were also performed. Furthermore, the relationship between the expressions of UC-related genes and infiltration of immune cells in the course of treatment was also investigated. Immunohistochemical (IHC) assay was used to verify the gene expression in inflamed UC tissues. When considering all the applied methods, DUOX2, PI3, S100P, MMP7, and S100A8 had priority to be defined as the characteristic genes among DEGs. The area under curve (AUC) of the five genes, which were all consistently over-expressed, based on an external validation dataset, were all above 0.94 for UC diagnosis. Four of the five genes (DUOX2, PI3, MMP7, and S100A8) were down-regulated between treatment-responsive and nonresponsive patients. A significant difference was also observed concerning the infiltration of immune cells, including macrophage and neutrophil, between the two groups (treatment responsive and nonresponsive). The changes in the expression of DUOX2 and MMP7 based on the IHC assay were highly consistent with the results obtained in the current study. This confirmed the mild to moderate diagnostic and predictive value of DUOX2 and MMP7 in patients with UC. The conducted analyses showed that the expression profile of the five identified biomarkers accurately detects UC, whereas four of the five genes evidently predicted the response to anti-TNF-α therapy.
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Colitis Ulcerosa , Factor de Necrosis Tumoral alfa , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/genética , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/patología , Factor de Necrosis Tumoral alfa/genética , Perfilación de la Expresión Génica , Biomarcadores/metabolismo , Pronóstico , Metaloproteinasa 7 de la Matriz/genética , Transcriptoma , Oxidasas Duales/genética , Oxidasas Duales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Femenino , Estudios de Casos y ControlesRESUMEN
Compared to the integer-order vector field, the fractional-order vector field has an additional degree of control freedom, which will bring rich photophysical properties and what we believe to be novel nonlinear optical phenomena. In this work, we theoretically and experimentally investigate the focusing, propagation, and spatial self-phase modulation (SSPM) of fractional-order linearly polarized vector fields (FLPVFs). It is shown that the weak focusing field of FLPVF exhibits an asymmetric intensity distribution. Intriguingly, its state of polarization (SoP) has a hybrid polarization distribution. When this focused FLPVF propagates to the far field in free space, its SoP degenerates into a localized linearly polarization distribution. However, after the focused FLPVF passes through an isotropic nonlinear Kerr medium, its SoP exhibits a hybrid polarization distribution. Additionally, unlike the self-diffraction intensity pattern of integer-order linearly polarized vector field (ILPVF) with a concentric multi-ring structure, the SSPM pattern of FLPVF is a symmetry broken self-diffraction intensity pattern. The presented work provides a nonlinear optics approach for manipulating both the SoP and intensity distributions of the light field.
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BACKGROUND: Podoplanin (PDPN) expressed on tumour cells interacts with platelet C-type lectin-like receptor 2 (CLEC-2). This study aimed to investigate the role of the PDPN-platelet CLEC-2 interaction in melanoma pulmonary metastasis. METHODS: Murine melanoma B16-F0 cells, which have two populations that express podoplanin, were sorted by FACS with anti-podoplanin staining to obtain purified PDPN + and PDPN- B16-F0 cells. C57BL/6J mice transplanted with CLEC-2-deficient bone marrow cells were used for in vivo experiments. RESULTS: The in vivo data showed that the number of metastatic lung nodules in WT mice injected with PDPN + cells was significantly higher than that in WT mice injected with PDPN- cells and in WT or CLEC-2 KO mice injected with PDPN- cells. In addition, our results revealed that the platelet Syk-dependent signalling pathway contributed to platelet aggregation and melanoma metastasis. CONCLUSIONS: Our study indicates that the PDPN-CLEC-2 interaction promotes experimental pulmonary metastasis in a mouse melanoma model. Tumour cell-induced platelet aggregation mediated by the interaction between PDPN and CLEC-2 is a key factor in melanoma pulmonary metastasis.
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Neoplasias Pulmonares , Melanoma , Animales , Ratones , Plaquetas/metabolismo , Lectinas Tipo C/metabolismo , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Ratones Endogámicos C57BL , Agregación PlaquetariaRESUMEN
A series of genipin derivatives were designed and synthesized as potential inhibitors targeted KRAS G12D mutation. The majority of these compounds demonstrated potential antiproliferative effects against KRAS G12D mutant tumor cells (CT26 and A427). Notably, seven compounds exhibited the anticancer effects with IC50 values ranging from 7.06 to 9.21 µM in CT26 (KRASG12D) and A427 (KRASG12D) cells and effectively suppressed the colony formation of CT26 cells. One representative compound SK12 was selected for further investigation into biological activity and action mechanisms. SK12 markedly induced apoptosis in CT26 cells in a concentration-dependent manner. Moreover, SK12 elevated the levels of reactive oxygen species (ROS) in tumor cells and exhibited a modulatory effect on the KRAS signaling pathway, thereby inhibiting the activation of downstream phosphorylated proteins. The binding affinity of SK12 to KRAS G12D protein was further confirmed by the surface plasmon resonance (SPR) assay with a binding KD of 157 µM. SK12 also exhibited notable anticancer efficacy in a nude mice tumor model. The relative tumor proliferation rate (T/C) of the experimental group (50 mg/kg) was 31.04 % (P < 0.05), while maintaining a commendable safety profile.
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Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Iridoides , Ratones Desnudos , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Iridoides/farmacología , Iridoides/química , Animales , Proteínas Proto-Oncogénicas p21(ras)/antagonistas & inhibidores , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Ratones , Estructura Molecular , Apoptosis/efectos de los fármacos , Descubrimiento de Drogas , Línea Celular Tumoral , Mutación , Ratones Endogámicos BALB C , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Neoplasias Experimentales/metabolismoRESUMEN
Background: Graves' ophthalmopathy (GO) is an organ-specific autoimmune disease and is a common orbital condition that can possibly lead to blindness. Objective: Our aim was to find out how patients with GO are affected in terms of quality of life (QoL) by traditional nursing care and social support mobile care. Methods: A total of 38 patients with GO who were admitted to Beijing Chao-Yang Hospital in China between December 2018 and December 2023 underwent life evaluations before treatment, 6 weeks after treatment and 6 months after treatment. The control group comprised 27 patients and the experimental group comprised 11 patients. They were then split into 2 groups based on the European Group on Graves' Orbitopathy (EUGOGO) improvement criteria: improved and unimproved. Then, the mean value of the Graves' Ophthalmopathy-Quality of Life Inventory (GO-QOL) alterations were compared to see if there was any difference, and their post-treatment QoL was examined. Results: (1) Patients who improved in this study had a mean change in visual energy scale scores before and after treatment that was higher than the patients who did not (13.39 vs 0.00, respectively); (2) The social functioning scores on the GO-QOL scale increased by 17.05 points in the control group before and after treatment (P < .01); (3) A total of 15.4% of patients had a GO-QOL score >90 after therapy, indicating a significant impact on their lives. In the experimental group, scores on the visual power energy scale improved by 16.27 points after treatment compared with before treatment (P = .028). Conclusion: When used in conjunction with traditional treatment, social supportive mobile care improves the outcomes in patients with GO and is superior to traditional care on its own.
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Background: Previous studies link overweight/obesity to reduced fertility, highlighting weight intervention as vital for better pregnancy outcomes. However, clarity on the role and efficacy of weight loss in enhancing pregnancy is inconsistent. Objective: This study aimed to assess the impact of individualized weight intervention on pregnancy among Chinese overweight/obese infertile women and explore body composition indexes influencing pregnancy outcomes. Methods: This retrospective study involved 363 overweight/obese infertile women admitted to the First Affiliated Hospital of Guangxi Medical University, Guangxi, China, from June 2017 to November 2020. Among them, 249 received personalized weight intervention (intervention group), while 114 did not (control group). Pregnancy outcomes were compared between the two groups, and changes in body composition before and after intervention were measured. Multivariate logistic regression was employed to analyze factors influencing pregnancy outcomes. Results: The intervention group exhibited significantly higher clinical pregnancy rates, natural pregnancy rates, assisted reproductive pregnancy rates, and induced ovulation (IO) pregnancy rates compared to the control group (all P < .05). Following weight intervention, there were significant decreases in body weight, body mass index (BMI), visceral fat area, and body fat (all P < .01). Logistic regression analysis identified polycystic ovary syndrome as the reason for infertility (OR=3.446, P = .016), ∆body weight %≥10% (OR=2.931, P = .014), and ∆visceral fat area% (OR=1.025, P = .047) as positive factors for a successful pregnancy. Conversely, age≥35 years old (OR=0.337, P = .001), BMI≥25 kg/m2 after intervention (OR=0.279, P < .001), and visceral fat area≥100 cm2 after intervention (OR=0.287, P = .007) were identified as negative factors. Conclusions: Individualized weight management enhances pregnancy outcomes in overweight/obese infertile women. Achieving a reduction in body weight by 10% or more, combined with effective control of visceral fat, proves important in improving pregnancy outcomes. Excess visceral fat emerges as an adverse factor impacting successful pregnancy.
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PURPOSE: This retrospective study aimed to investigate whether the repair of medial meniscus posterior root tears (MMPRTs) is effective for improving clinical outcomes and return to sports rates in young patients (50 years old or younger) with medial compartment knee osteoarthritis (KOA) and MMPRTs. METHODS: Between 2016 and 2019, 153 patients with KOA and MMPRTs who underwent open-wedge high tibial osteotomy (OWHTO) were retrospectively included. The patients were divided into OWHTO combined with MMPRT repair (n = 73) and isolated OWHTO (n = 80) groups. Lysholm scores, Hospital for Special Surgery (HHS) scores, Tegner scores, flexion contracture, range of knee flexion, return to sports rates and postoperative complications were compared. Radiological outcomes, including hip-knee-ankle angle (HKA), medial proximal tibial angle (MPTA), joint line convergence angle (JLCA) and Kellgren-Lawrence (K-L) grade, were compared between the two groups. RESULTS: After a mean follow-up of 30.1 ± 3.0 months, the OWHTO + Repair group observed better clinical outcomes compared with the OWHTO group (Lysholm score: 86.7 ± 7.4 vs. 81.6 ± 6.9, p = 0.023. HHS score: 85.4 ± 8.20 vs. 80.5 ± 7.1, p = 0.039). The OWHTO + Repair group had higher Tegner scores and return to sports rates than the OWHTO group (Tegner score: 6 vs. 5, p = 0.020; return to sports rates: 38% vs. 15%, p = 0.001). No fracture or major complications occurred. Radiological outcomes showed no significant differences between the two groups (HKA: 181.1 ± 2.7 vs. 180.1 ± 1.5 n.s; MPTA: 90.1 ± 1.8 vs. 89.2 ± 1.4, n.s; JLCA:1.9 ± 0.7 vs. 2.1 ± 0.7, n.s). CONCLUSIONS: Additional MMPRT repair during OWHTO was associated with better clinical outcomes and higher rates of return to sports in young patients with medial compartment KOA and MMPRTs. LEVEL OF EVIDENCE: Level III.
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Osteoartritis de la Rodilla , Osteotomía , Volver al Deporte , Tibia , Lesiones de Menisco Tibial , Humanos , Estudios Retrospectivos , Osteotomía/métodos , Masculino , Femenino , Osteoartritis de la Rodilla/cirugía , Lesiones de Menisco Tibial/cirugía , Persona de Mediana Edad , Tibia/cirugía , Adulto , Resultado del Tratamiento , Rango del Movimiento Articular , Complicaciones Posoperatorias/epidemiologíaRESUMEN
A new method of efficiently transforming water vapor into hydrogen was investigated by dielectric barrier discharge (DBD) loaded with bamboo carbon bed structured by fibrous material in an argon medium. Hydrogen productivity was measured in three different reactors: a non-loaded DBD (N-DBD), a bamboo carbon (BC) bed DBD (BC-DBD), and a quartz wool (QW)-loaded BC DBD (QC-DBD). The effects of the quality ratio of BC to QW and relative humidity on hydrogen productivity were also investigated in QC-DBD at various flow rates. The reaction process and mechanism were analyzed by scanning electron microscopy, X-ray photoelectron spectroscopy, N2 physisorption experiments, infrared spectroscopy, and optical emission spectroscopy. A new reaction pathway was developed by loading BC into the fibrous structured material to activate the reaction molecules and capture the O-containing groups in the DBD reactor. A hydrogen productivity of 17.3 g/kWh was achieved at an applied voltage of 5 kV, flow rate of 4 L/min, and 100% relative humidity (RH) in the QC-DBD with a quality ratio of BC to QW of 3.0.
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"Internetâ +â Nursing" refers to medical institutions using Internet technologies and big data to provide nursing services to discharged patients or those with severe illnesses unable to visit hospitals, through online applications and offline care provision. This study aimed to explore the influence of "Internetâ +â Nursing" on the psychological status and quality of life of patients with thyroid eye disease. Sixty-eight patients with thyroid eye disease from January 2021 to December 2022 were divided into a research group (n = 34, joined the platform) and control group (n = 34, not joined the platform) based on their voluntary participation in our hospital's "Internetâ +â Nursing Platform." The self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < .05). The short form-36 health survey (SF-36) scores in various dimensions were higher in the research group compared to the control group (Pâ <â .05). The incidence rates of retinal detachment, vitreous hemorrhage, diabetic retinopathy, and iris neovascularization were lower in the research group compared to the control group (P < .05). After nursing, exophthalmos, blink frequency, and eyelid height of the research group were lower than those of the control group, while tear film breakup time was higher than that of the control group (P < .05). The visual acuity of the research group was higher than that of the control group (P < .05). After nursing, the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) scores in various dimensions were significantly higher in the research group than those in the control group (P < .05). Additionally, after nursing, the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) in the research group were lower than those in the control group (P < .05). The patients in the research group exhibited higher recognition scores of nursing compared to those in the control group (P < .05). Through the implementation of "Internetâ +â Nursing" for patients with thyroid eye disease discharged from our hospital, we can provide better out-of-hospital nursing for patients, reduce the occurrence of complications, improve ocular surface symptoms, promote visual acuity recovery, and improve patients' psychological status and quality of life.
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Calidad de Vida , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Internet , Oftalmopatía de Graves/psicología , AncianoRESUMEN
There are over 533 nucleosome structures in the Research Collaboratory for Structural Bioinformatics (RCSB). Collectively, numerous variants and species are present, as are sub-nucleosomal and super-nucleosomal assemblies within the nucleosome family. The organization of the histones and DNA is highly conserved in all standard octasomes containing 145, 146, or 147 base pairs. This observation is used to establish a nucleosome reference frame that enables us to describe and compare the gross structure and organization of all nucleosomes. We observe that cumulative sums of Rise, Twist, and DNA arc length are linear functions of the base pair index with R 2 values exceeding 0.999 for almost all octasome structures. These relationships enable us to readily compare the location and orientation of DNA director frames extracted from the crystal structures to ideal superhelix values. Such comparisons reveal that the DNA superhelix extracted from X-ray structures exhibits a sinusoidal variation with an amplitude of approximately 5Å about a constant superhelix radius of â¼ 42 Å, in agreement with early descriptions of nucleosome organization as tripartite. There is also a distinct straightening of the nucleosomal DNA over the outermost turn of DNA's double helix. The straightening of the DNA superhelix marks the transition to linker DNA and is easily recognized as a rapid increase in superhelix radius and is concomitant with a change in pitch. This provides a rigorous means of separating nucleosomal DNA from linker DNA. For all X-ray structures, we find that near the dyad, there exists a set of DNA director frames for which the spatial location and orientation are highly conserved. Away from the dyad, the DNA superhelix exhibits "singletrack" and "multipath" regions. In the singletrack region, all structures exhibit a single highly conserved pathway along which all base pairs must track, but at varying rates. In the multipath regions, the base pairs are allowed to map out a limited number of different pathways along the surface of the histone octamer. To demonstrate the utility of the proposed reference geometries, standard and distorted octasome structures, super-nucleosomal structures, nucleosomes with linker DNA, and nucleosomes in closed circular DNA are analyzed. Supplementary Information: The online version contains supplementary material available at 10.1007/s12551-024-01206-5.
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From the 4 perspectives of T lymphocytes, various cytokines, adenosine and "neuro-endocrine-immune" network, the researches related to the immune mechanism of acupuncture and moxibustion in the treatment of rheumatoid arthritis (RA) in recent years were summarized, and different acupuncture and moxibustion treatments were analyzed. The method has a regulatory effect on the mechanism of RA, in order to provide a reference and basis for acupuncture research on the immune mechanism of RA, and promote the further development of research in this field.
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Terapia por Acupuntura , Acupuntura , Artritis Reumatoide , Moxibustión , Humanos , Moxibustión/métodos , Artritis Reumatoide/terapia , CitocinasRESUMEN
The key to the treatment of multiple sclerosis (MS) is to promote the transition from inflammation-induced demyelination to remyelination. Polarization of microglia towards M1 or M2 phenotype is critical in this transition. Interferon induced protein with tetratricopeptide repeats 3 (IFIT3) is involved in inflammatory reaction and up-regulated in M1-polarized macrophages. However, its effect on microglia during MS has not been reported. In this paper, we demonstrated the important role of IFIT3 in selectively regulating microglia polarization. The expression of IFIT3 was increased when microglia were polarized towards M1, but did not change under M2 polarization. The knockdown of IFIT3 selectively inhibited M1 polarization, while M2 polarization was not affected by IFIT3 silencing. Furthermore, the activation of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa-B (NF-ĸB) signaling in M1 polarized microglia was suppressed by downregulating IFIT3. In experimental autoimmune encephalitis (EAE) mice, an animal model of MS, IFIT3 expression was upregulated. The disease progression, inflammatory infiltration and demyelination in the EAE mice were alleviated by silencing IFIT3. The inhibitory effects of IFIT3 knockdown on M1 polarization and STAT1 and NF-ĸB pathways were also confirmed in the spinal cord of EAE mice. In summary, our findings suggest that IFIT3 selectively intensified microglia polarization towards the pro-inflammatory M1 phenotype, and may contribute to the progression of MS.
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Encefalomielitis Autoinmune Experimental , Esclerosis Múltiple , Animales , Ratones , Inflamación/metabolismo , Ratones Endogámicos C57BL , Microglía/metabolismo , Esclerosis Múltiple/metabolismo , FN-kappa B/metabolismoRESUMEN
OBJECTIVE: All-inside and standard techniques with 4-strand hamstrings graft have been widely used in anterior cruciate ligament (ACL) reconstruction. However, the graft diameter of less than 8 mm will significantly increase the rate of surgical failure, and the 6-strand graft can solve this problem. The purpose of this study is to compare all-inside ACL reconstruction using suspensory cortical button fixation on both tibia and femur with standard ACL reconstruction using suspensory femoral fixation and a bioabsorbable tibial interference screw with a 6-strand hamstring tendon autograft in postoperative clinical outcomes. METHODS: From January 2020 to December 2020, 48 patients performed ACL reconstruction were divided into the all-side group and the standard group according to the different surgical techniques. Magnetic resonance imaging (MRI) and subjective function scores was used to assess clinical outcomes at least 24 months following ACL reconstruction. MRI was used to measure the value of bone tunnel widening in articular and middle portions. Subjective function scores included the Lysholm knee score, the International Knee Documentation Committee (IKDC) score, the Knee Society Score (KSS) for pain and function, and KT-1000. The t-test was used assuming the distribution of the patients which follows the normal distribution and we used non-parametric tests if these two conditions were not satisfied. RESULTS: At the final follow-up, there were 22 patients in the all-inside group and 24 patients in the standard group. No significant differences were found with respect to femoral tunnel widening and subjective function scores. However, a significant increase in tibial tunnel widening was found in the middle portion of the standard group (2.25 ± 0.74) compared to the all-inside group (0.76 ± 0.24) (p < 0.01) and also in the articular portion of the standard group (2.07 ± 0.77) compared to the all-inside group (1.52 ± 0.54) (p = 0.02). In addition, the value of the KT-1000 was 1.81 ± 0.45 for the all-inside group and 2.12 ± 0.44 in the standard group (p = 0.016). CONCLUSION: The objective stability of the knee was relatively better in the all-inside group than in the standard group. And tunnel widening after ACL reconstruction was significantly greater in the standard technique when compared to the all-inside technique on the tibia side.
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Reconstrucción del Ligamento Cruzado Anterior , Tendones Isquiotibiales , Humanos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Masculino , Adulto , Femenino , Tendones Isquiotibiales/trasplante , Adulto Joven , Autoinjertos , Estudios Retrospectivos , Trasplante Autólogo , Imagen por Resonancia Magnética , AdolescenteRESUMEN
Background: Burns are a prevalent form of unintentional injury and a significant public health concern in developing countries. We aimed to investigate the epidemiological and clinical characteristics of adult burn patients at a major center in Eastern China. Methods: This 6-year retrospective study analyzed patients with varying degrees of burns between January 2017 and December 2022 at the Suzhou Burns and Trauma Center. The study extracted demographic, clinical, and epidemiological data from electronic medical records for analysis. Results: The study included 3,258 adult patients, of which 64.3% were male. The largest age group affected 30-59-year-old adults (63.04%). Scalds were the leading cause of burns (1,346, 41.31%), followed by flames (1,271, 39.01%). The majority of burn hospitalizations were those with moderate burns (1791, 54.97%). The morbidity rate was low at 0.68%, while mortality was strongly associated with age, etiology, and total body surface area. Patients with certain types of burns, such as explosions, hot crush injuries, and electric burns had more operations, longer lengths of hospital stay, and higher costs compared to those with scalds and flame injuries. Conclusion: Different prevention strategies should be formulated according to different etiologies, ages, and genders.
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Unidades de Quemados , Quemaduras , Humanos , Masculino , Estudios Retrospectivos , Quemaduras/epidemiología , China/epidemiología , Adulto , Femenino , Persona de Mediana Edad , Unidades de Quemados/estadística & datos numéricos , Anciano , Adulto Joven , Hospitalización/estadística & datos numéricos , Adolescente , Tiempo de Internación/estadística & datos numéricosRESUMEN
BACKGROUND: NDRG1, the first member of the NDRG family, is a multifunctional protein associated with carcinogenesis. Its function in human cancer is currently poorly understood. The aim of this study was to explore the importance of NDRG1 in tumor immune cell infiltration and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma. METHODS: NDRG1 expression in various cancers was analyzed using TIMER 2.0, the Human Protein Atlas (HPA), UALCAN and PrognoScan. Wound healing, Transwell, MTT and colony formation assays were performed to confirm the effects of NDRG1 on the metastasis and proliferation of HCC cells. Western blotting was used to study the effect of NDRG1 on the expression of EMT-related proteins. Signaling networks were constructed using LinkedOmics and Metascape. TIMER2.0 and TISIDB were used for comprehensive analysis of tumor-infiltrating immune cells and tumor-infiltrating lymphocytes (TILs). RESULT: NDRG1 expression was higher in HCC tissue than in normal liver tissue at both the mRNA and protein levels. Overexpression of NDRG1 is associated with poor prognosis in HCC patients. Genomic analysis suggests that NDRG1 promoter hypermethylation leads to enhanced transcription, which may be one mechanism for NDRG1 upregulation in HCC. The overexpression of NDRG1 promotes the invasion, migration, and proliferation of HCC cells and induces the expression of EMT-related proteins. Immunoinfiltration analysis suggests that NDRG1 is involved in the recruitment of immune cells. CONCLUSIONS: The present study showed that NDRG1 may induce metastasis and invasion through EMT and immune cell infiltration. NDRG1 could be used as a biomarker for the diagnosis and prognosis of HCC and could be a potential therapeutic target in HCC.
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Carcinoma Hepatocelular , Proteínas de Ciclo Celular , Transición Epitelial-Mesenquimal , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Transición Epitelial-Mesenquimal/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Pronóstico , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Línea Celular Tumoral , Linfocitos Infiltrantes de Tumor/inmunología , Regulación Neoplásica de la Expresión Génica , Proliferación Celular/genética , Masculino , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Movimiento Celular/genética , FemeninoRESUMEN
This study aimed to assess the efficacy and safety of esaxerenone (CS-3150) in treating primary hypertension. PubMed (Medline), Cochrane Central Register of Controlled Trials (CENTRAL), and Embase databases were searched for articles published until April 18, 2023. The outcomes included were diastolic blood pressure (DBP), systolic blood pressure (SBP), 24 h DBP, 24 h SBP, and adverse events. The meta-analysis was conducted using RevMan 5.3. This study included three trials. CS-3150 5 mg had a greater effect on lowering the SBP, DBP, 24 h SBP, and 24 h DBP than either CS-3150 2.5 mg or eplerenone 50 mg. In contrast, CS-3150 2.5 mg and eplerenone 50 mg showed no significant difference in lowering DBP, SBP, 24 h DBP, and 24 h SBP. Moreover, adverse events occurred at comparable rates in the three groups. CS-3150 (especially CS-3150 5 mg) is an effective and safe treatment for primary hypertension; which can reduce blood pressure and alleviate hypertensive symptoms.
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Antihipertensivos , Presión Sanguínea , Hipertensión , Humanos , Antihipertensivos/uso terapéutico , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Pirroles/uso terapéutico , Pirroles/efectos adversos , Sulfonas/efectos adversos , Sulfonas/uso terapéutico , Persona de Mediana Edad , Hipertensión Esencial/tratamiento farmacológico , Hipertensión Esencial/fisiopatología , Hipertensión Esencial/diagnóstico , Masculino , FemeninoRESUMEN
BACKGROUND: Oxidative stress, propelled by reactive oxygen species (ROS), serves as a significant catalyst for atherosclerosis (AS), a primary contributor to vascular diseases on a global scale. Antioxidant therapy via nanomedicine has emerged as a pivotal approach in AS treatment. Nonetheless, challenges such as inadequate targeting, subpar biocompatibility, and limited antioxidant effectiveness have restrained the widespread utilization of nanomedicines in AS treatment. This study aimed to synthesize a specialized peptide-modified liposome capable of encapsulating two antioxidant enzymes, intending to enhance targeted antioxidant therapy for AS. METHODS: The film dispersion method was employed for liposome preparation. Fluorescence quantification was conducted to assess the drug encapsulation rate. Characterization of liposome particle size was performed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Laser confocal microscopy and flow cytometry were utilized to analyze liposome cell uptake and target foam cells. Antioxidant analysis was conducted using 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining, while pro-lipid efflux analysis utilized Oil Red O (ORO) staining. Safety evaluation was performed using Hematoxylin and Eosin (H&E) staining. The level of inflammatory factors was determined through enzyme-linked immunosorbent assay (ELISA). The degree of lipid oxidation at the cellular level was assessed using the malonaldehyde (MDA) assay. In vivo targeting analysis was conducted using small animal live imaging. RESULTS: Our in vitro and in vivo findings substantiated that the modification of Lyp-1 led to increased delivery of antioxidant enzymes into foam cells (p < 0.05), the primary pathological cells within AS plaques. Upon accumulation in foam cells, liposomes loaded with superoxide dismutase (SOD) and catalase (CAT) (LyP-lip@SOD/CAT) effectively mitigated excess ROS and shielded macrophages from ROS-induced damage (p < 0.01). Furthermore, the reduction in ROS levels notably hindered the endocytosis of oxidized low-density lipoprotein (Ox-LDL) by activated macrophages, subsequently alleviating lipid accumulation at atherosclerotic lesion sites, evident from both in vitro and in vivo ORO staining results (p < 0.01). LyP-lip@SOD/CAT significantly curbed the secretion of inflammatory factors at the plaque site (p < 0.001). Additionally, LyP-lip@SOD/CAT demonstrated commendable biological safety. CONCLUSIONS: In this study, we effectively synthesized LyP-lip@SOD/CAT and established its efficacy as a straightforward and promising nano-agent for antioxidant therapy targeting atherosclerosis.
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Aterosclerosis , Placa Aterosclerótica , Animales , Células Espumosas , Liposomas/farmacología , Superóxido Dismutasa/farmacología , Catalasa/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Estrés Oxidativo , Aterosclerosis/tratamiento farmacológico , Lipoproteínas LDL/farmacologíaRESUMEN
In abdominal wall defect repair, surgical site infection (SSI) remains the primary cause of failure, while complications like visceral adhesions present significant challenges following patch implantation. We designed a Janus multifunctional hydrogel patch (JMP) with antibacterial, anti-inflammatory, and anti-adhesive properties. The patch comprises two distinct layers: a pro-healing layer and an anti-adhesion layer. The pro-healing layer was created by a simple mixture of polyvinyl alcohol (PVA), quaternized chitosan (QCS), and gallic acid (GA), crosslinked to form PVA/QCS/GA (PQG) hydrogels through GA's self-assembly effect and hydrogen bonding. Additionally, the PVA anti-adhesive layer was constructed using a drying-assisted salting method, providing a smooth and dense physical barrier to prevent visceral adhesion while offering essential mechanical support to the abdominal wall. The hydrogel patch demonstrates widely adjustable mechanical properties, exceptional biocompatibility, and potent antimicrobial properties, along with a sustained and stable release of antioxidants. In rat models of skin and abdominal wall defects, the JMP effectively promoted tissue healing by controlling infection, inhibiting inflammation, stimulating neovascularization, and successfully preventing the formation of visceral adhesions. These compelling results highlight the JMP's potential to improve the success rate of abdominal wall defect repair and reduce surgical complications.
Asunto(s)
Pared Abdominal , Quitosano , Ratas , Animales , Hidrogeles/farmacología , Alcohol Polivinílico , Ácido Gálico , Pared Abdominal/cirugía , Antibacterianos/farmacología , Adhesivos , Adherencias Tisulares/prevención & controlRESUMEN
Background: Bacterial infections pose a considerable threat to skin wounds, particularly in the case of challenging-to-treat diabetic wounds. Systemic antibiotics often struggle to penetrate deep wound tissues and topically applied antibiotics may lead to sensitization, necessitating the development of novel approaches for effectively treating germs in deep wound tissues. Neutrophils, the predominant immune cells in the bloodstream, rapidly release an abundance of molecules via degranulation upon activation, which possess the ability to directly eliminate pathogens. This study was designed to develop novel neutrophil cell engineered nanovesicles (NVs) with high production and explore their bactericidal properties and application in promoting infectious wound healing. Methods: Neutrophils were isolated from peripheral blood and activated in vitro via phorbol myristate acetate (PMA) stimulation. Engineered NVs were prepared by sequentially extruding activated neutrophils followed by ultracentrifugation and were compared with neutrophil-derived exosomes in terms of morphology, size distribution and protein contents. The bactericidal effect of NVs in vitro was evaluated using the spread plate technique, LIVE/DEAD backlight bacteria assay and observation of bacterial morphology. The therapeutic effects of NVs in vivo were evaluated using wound contraction area measurements, histopathological examinations, assessments of inflammatory factors and immunochemical staining. Results: Activated neutrophils stimulated with PMA in vitro promptly release a substantial amount of bactericidal proteins. NVs are similar to exosomes in terms of morphology and particle size, but they exhibit a significantly higher enrichment of bactericidal proteins. In vitro, NVs demonstrated a significant bactericidal effect, presumably mediated by the enrichment of bactericidal proteins such as lysozyme. These NVs significantly accelerated wound healing, leading to a marked reduction in bacterial load, downregulation of inflammatory factors and enhanced collagen deposition in a full-thickness infectious skin defect model. Conclusions: We developed engineered NVs derived from activated neutrophils to serve as a novel debridement method targeting bacteria in deep tissues, ultimately promoting infectious wound healing.
RESUMEN
To explore the characteristics of hematologic indicators and related risk factors of lower extremity deep vein thrombosis (LDVT) in patients with cerebral infarction. METHODS: This study retrospectively analyzed data from 174 patients with cerebral infarction admitted to The Rehabilitation Department of Shanghai Fifth Rehabilitation Hospital and Shanghai First People's Hospital from June 2022 to June 2023. Based on the results of lower limb venous color Doppler ultrasound examinations, patients were divided into two groups: the LDVT group (35 cases) and the non-LDVT group (139 cases). We compared the clinical data and hematologic indicators (D-dimer value, fibrinogen, white blood cells, platelets, uric acid, creatinine, etc.) of the two groups to identify the risk factors of cerebral infarction complicated with LDVT. RESULTS: Statistical analysis revealed that the D-dimer values of the LDVT group were significantly (P<0.05) higher than those of the non-LDVT group. The uric acid value of the LDVT group was significantly lower than that of the non-LDVT group, with statistical significance (P<0.05). The Brunnstrom staging in the LDVT group was significantly different from that in the non-LDVT group (P<0.05). Meanwhile, binary logistic regression analysis showed that LDVT complicated with cerebral infarction was associated with D-dimer level [OR=1.302, 95% CI (1.077, 1.575)], uric acid level [OR=0.995, 95% CI (0.990, 1.000)], and Brunnstrom staging [OR=3.005, 95% CI (1.312, 6.880)]. CONCLUSION: D-dimer value, uric acid value, and Brunnstrom stage I to II are closely related to the occurrence of LDVT in patients with cerebral infarction. High D-dimer value, low uric acid value, and Brunnstrom stage I to II are independent risk factors for LDVT in cerebral infarction. Early assessment of D-dimer value, uric acid value, and Brunnstrom stage of cerebral infarction should be considered in clinical practice.