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1.
Front Public Health ; 12: 1413986, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989128

RESUMO

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.


Assuntos
Unidades de Queimados , Queimaduras , Humanos , Masculino , Estudos Retrospectivos , Queimaduras/epidemiologia , China/epidemiologia , Adulto , Feminino , Pessoa de Meia-Idade , Unidades de Queimados/estatística & dados numéricos , Idoso , Adulto Jovem , Hospitalização/estatística & dados numéricos , Adolescente , Tempo de Internação/estatística & dados numéricos
2.
Artigo em Inglês | MEDLINE | ID: mdl-38843425

RESUMO

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.

3.
Burns Trauma ; 12: tkae018, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38903935

RESUMO

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.

4.
Mol Immunol ; 172: 17-22, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38865800

RESUMO

Acute myocardial infarction (AMI), mainly triggered by vascular occlusion or thrombosis, is the most prevalent cause of morbidity and mortality among all cardiovascular diseases. The devastating consequences of AMI are further aggravated by the intricate cellular processes involved in inflammation. In the past two decades, many studies have reported that regulatory T cells (Tregs), as the main immunoregulatory cells, play a crucial role in AMI progression. This review offers a comprehensive insight into the intricate relationship between Tregs and AMI development. Moreover, it explores emerging therapeutic strategies that focus on Tregs and their exosomes. Furthermore, we underscore the importance of employing noninvasive in vivo imaging techniques to advance the clinical applications of Tregs-based treatments in AMI. Although further research is essential to fully elucidate the molecular mechanisms underlying the effects of Tregs, therapies tailored to these cells hold immense potential for the treatment of patients with AMI.

5.
Cell Signal ; 120: 111197, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38697447

RESUMO

OBJECTIVES: The clinical T1 stage solid lung cancer with metastasis is a serious threat to human life and health. In this study, we performed RNA sequencing on T1 advanced-stage lung cancer and adjacent tissues to identify a novel biomarker and explore its roles in lung cancer. METHODS: Quantitative reversed-transcription PCR, reverse transcription PCR and Western blot, MSP and Methtarget were utilized to evaluate FIBIN expression levels at both the transcriptional and protein levels as well as its methylation status. Differential target protein was evaluated for relative and absolute quantitation by isobaric tags. Co-IP was performed to detect the interactions between target protein. Precise location and expression levels of target proteins were revealed by immunofluorescence staining and component protein extraction using specific kits, respectively. RESULTS: We reported that FIBIN was frequently silenced due to promoter hypermethylation in lung cancer. Additionally, both in vitro and in vivo experiments confirmed the significant anti-proliferation and anti-metastasis capabilities of FIBIN. Mechanistically, FIBIN decreased the nuclear accumulation of ß-catenin by reducing the binding activity of GSK3ß with ANXA2 while promoting interaction between GSK3ß and ß-catenin. CONCLUSION: Our findings firstly identify FIBIN is a tumor suppressor, frequently silenced due to promoter hypermethylation. FIBIN may serve as a predictive biomarker for progression or metastasis among early-stage lung cancer patients.


Assuntos
Anexina A2 , Carcinoma Pulmonar de Células não Pequenas , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Anexina A2/metabolismo , Anexina A2/genética , Animais , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos Nus , Metástase Neoplásica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Masculino , Regiões Promotoras Genéticas/genética , Feminino , Camundongos Endogâmicos BALB C , Células A549 , Movimento Celular
6.
Bioorg Chem ; 148: 107460, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781668

RESUMO

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.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Iridoides , Camundongos Nus , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Iridoides/farmacologia , Iridoides/química , Animais , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos , Estrutura Molecular , Apoptose/efeitos dos fármacos , Descoberta de Drogas , Linhagem Celular Tumoral , Mutação , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-38643405

RESUMO

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.

8.
BMC Cancer ; 24(1): 399, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561690

RESUMO

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.


Assuntos
Neoplasias Pulmonares , Melanoma , Animais , Camundongos , Plaquetas/metabolismo , Lectinas Tipo C/metabolismo , Neoplasias Pulmonares/metabolismo , Melanoma/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Agregação Plaquetária
9.
Medicine (Baltimore) ; 103(17): e37974, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669376

RESUMO

"Internet + 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 "Internet + 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 "Internet + 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 (P < .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 "Internet + 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.


Assuntos
Qualidade de Vida , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Internet , Oftalmopatia de Graves/psicologia , Idoso
10.
Orthop Surg ; 16(5): 1034-1041, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38506183

RESUMO

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.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Masculino , Adulto , Feminino , Tendões dos Músculos Isquiotibiais/transplante , Adulto Jovem , Autoenxertos , Estudos Retrospectivos , Transplante Autólogo , Imageamento por Ressonância Magnética , Adolescente
12.
ACS Appl Mater Interfaces ; 16(11): 13496-13508, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38449094

RESUMO

Atherosclerosis is a chronic inflammatory disease characterized by the formation of atherosclerotic plaques, while macrophages as key players in plaque progression and destabilization are promising targets for atherosclerotic plaque imaging. Contrast-enhanced magnetic resonance imaging (CE-MRI) has emerged as a powerful noninvasive imaging technique for the evaluation of atherosclerotic plaques within arterial walls. However, the visualization of macrophages within atherosclerotic plaques presents considerable challenges due to the intricate pathophysiology of the disease and the dynamic behavior of these cells. Biocompatible ferrite nanoparticles with diverse surface ligands possess the potential to exhibit distinct relaxivity and cellular affinity, enabling improved imaging capabilities for macrophages in atherosclerosis. In this work, we report macrophage-affinity nanoparticles for magnetic resonance imaging (MRI) of atherosclerosis via tailoring nanoparticle surface coating. The ultrasmall zinc ferrite nanoparticles (Zn0.4Fe2.6O4) as T1 contrast agents were synthesized and modified with dopamine, 3,4-dihydroxyhydrocinnamic acid, and phosphorylated polyethylene glycol to adjust their surface charges to be positively, negatively, and neutrally charged, respectively. In vitro MRI evaluation shows that the T1 relaxivity for different surface charged Zn0.4Fe2.6O4 nanoparticles was three higher than that of the clinically used Gd-DTPA. Furthermore, in vivo atherosclerotic plaque MR imaging indicates that positively charged Zn0.4Fe2.6O4 showed superior MRI efficacy on carotid atherosclerosis than the other two, which is ascribed to high affinity to macrophages of positively charged nanoparticles. This work provides improved diagnostic capability and a better understanding of the molecular imaging of atherosclerosis.


Assuntos
Aterosclerose , Compostos Férricos , Nanopartículas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia , Zinco , Aterosclerose/patologia , Meios de Contraste , Imageamento por Ressonância Magnética/métodos , Macrófagos/patologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-38551442

RESUMO

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.

14.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(1): 93-97, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38404281

RESUMO

Hemorrhagic shock (HS) is one of the leading causes of death among young adults worldwide. Multiple organ dysfunction in HS is caused by an imbalance between tissue oxygen supply and demand, which is closely related to the poor prognosis of patient. Mitochondrial dysfunction is one of the key mechanisms contributing to multiple organ dysfunction in HS, while mitochondrial quality control regulates mitochondrial function through a series of processes, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial-derived vesicles, and mitochondrial protein homeostasis. Modulating mitochondrial quality control can improve organ dysfunction. This review aims to summarize the effects of mitochondrial dysfunction on organ function in HS and discuss the potential mechanisms of mitochondrial quality control, providing insights into the injury mechanisms underlying HS and guiding clinical management.


Assuntos
Doenças Mitocondriais , Choque Hemorrágico , Adulto Jovem , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Choque Hemorrágico/complicações , Mitocôndrias , Doenças Mitocondriais/complicações , Doenças Mitocondriais/metabolismo
15.
Discov Med ; 36(181): 343-354, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38409839

RESUMO

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.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Células Espumosas , Lipossomos/farmacologia , Superóxido Dismutase/farmacologia , Catalase/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Estresse Oxidativo , Aterosclerose/tratamento farmacológico , Lipoproteínas LDL/farmacologia
16.
Int J Biol Macromol ; 263(Pt 1): 130291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38378119

RESUMO

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.


Assuntos
Parede Abdominal , Quitosana , Ratos , Animais , Hidrogéis/farmacologia , Álcool de Polivinil , Ácido Gálico , Parede Abdominal/cirurgia , Antibacterianos/farmacologia , Adesivos , Aderências Teciduais/prevenção & controle
17.
Nat Prod Res ; : 1-7, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300732

RESUMO

Two new acorane-type sesquiterpenoids, harzianes A and B (1 and 2), together with two known cyclonerodiol-type sesquiterpenoids (3-4) and four known sterols (5-8) were isolated from the endophytic Trichoderma harzianum, associated with the medicinal plant Paeonia lactiflora Pall. Compounds 1 and 2 were identified as a pair of heterotropic isomers by spectroscopic analysis (HR-ESI-MS, 1D and 2D NMR), and their absolute configurations were determined by ECD calculations. All compounds were tested for anti-inflammatory activity, however, none demonstrated such activity.

18.
Orthop J Sports Med ; 12(1): 23259671231225671, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304055

RESUMO

Background: Surgical correction for recurrent patellar dislocation (RPD) can improve femoral trochlear morphology; nonetheless, the effects of surgical correction on femoral condyle morphology are unclear. Purpose: To investigate the morphological changes in the posterior femoral condyle in skeletally immature patients with RPD and trochlear dysplasia (TD) after surgical correction. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 20 skeletally immature patients with bilateral RPD and TD were included in this study. For each patient, the knee that was dislocated more frequently or had sustained a recent injury was treated with medial patellar retinaculum plasty (group S; n = 20 knees), and the asymptomatic or only occasionally dislocated contralateral knee was treated conservatively (group C; n = 20 knees). The lengths of the anterior medial and lateral femoral condyles and the lengths of the posterior medial and lateral femoral condyles were evaluated preoperatively and at the final follow-up. Trochlear morphological characteristics, tibial tuberosity-trochlear groove distance, and patellar tilt angle were compared between preoperative and final follow-up values with the 2-sample paired Student t test and were compared between groups S and C with the independent-samples t test. Results: The mean follow-up time was 60.7 ± 4.8 months. No knee in group S experienced a redislocation, whereas 80% (16/20) of knees in group C experienced a dislocation. There were significant group differences in the ratio of the posterior medial femoral condyle (PMFC) to the posterior lateral femoral condyle (PLFC) (group S, 1.08 ± 0.05; group C, 1.14 ± 0.06; P = .042). There was no significant difference in the ratio of the anterior lateral femoral condyle to the anterior medial femoral condyle (group S, 1.16 ± 0.13; group C, 1.18 ± 0.09; P = .635). In group S, all trochlear morphological characteristics and patellofemoral joint characteristics improved compared with preoperatively (P≤ .047 for all). In addition, all values significantly differed between groups S and C at the final follow-up (P≤ .044 for all). Conclusion: The study findings demonstrated that the morphology of the posterior femoral condyle in skeletally immature patients with bilateral RPD and TD changes after surgical correction, with the PLFC growing faster than the PMFC.

19.
IUBMB Life ; 76(7): 451-463, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38269750

RESUMO

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.


Assuntos
Colite Ulcerativa , Fator de Necrose Tumoral alfa , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/patologia , Fator de Necrose Tumoral alfa/genética , Perfilação da Expressão Gênica , Biomarcadores/metabolismo , Prognóstico , Metaloproteinase 7 da Matriz/genética , Transcriptoma , Oxidases Duais/genética , Oxidases Duais/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Feminino , Estudos de Casos e Controles
20.
Dig Liver Dis ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38290958

RESUMO

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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