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1.
Materials (Basel) ; 17(15)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39124435

RESUMO

The arc torch angle greatly affected the deposition characteristics in the wire arc additive manufacturing (WAAM) process, and the relation between the droplet transition behavior and macrostructure morphology was unclear. This work researched the effect of torch angle on the formation accuracy, droplet transition behavior and the mechanical properties in the WAAM process on a ZL205A aluminum alloy. The results suggested that at the obtuse torch angle, part of the energy input was used to heat the existing molten pool, which was optimized for the longer solidification period of the molten pool. Therefore, the greater layer penetration depth at 100° resulted in the improved layer-by-layer combination ability. The obtuse torch angle was associated with the better formation accuracy on the sidewall surface due to the smaller impact on the molten pool, which was influenced by both the arc pressure and droplet impact force. The eliminated pores were optimized for the mechanical properties of depositions at a torch angle of 100°; thus, the tensile strength and elongation attained maximum values of 258.6 MPa and 17.1%, respectively. These aspects made WAAM an attractive mode for manufacturing large structural components on ZL205A aluminum alloy.

3.
Biomed Pharmacother ; 177: 117002, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38960836

RESUMO

This review provides an in-depth examination of the role that tumor-associated macrophages (TAMs) play in the progression of prostate cancer (PCa), with a particular focus on the factors influencing the polarization of M1 and M2 macrophages and the implications of targeting these cells for cancer progression. The development and prognosis of PCa are significantly influenced by the behavior of macrophages within the tumor microenvironment. M1 macrophages typically exhibit anti-tumor properties by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), thereby enhancing the immune response. Conversely, M2 macrophages contribute to tumor cell migration and invasion through the production of factors like arginase-1 (Arg1) and interleukin-10 (IL-10). This review not only explores the diverse factors that affect macrophage polarization but also delves into the potential therapeutic strategies targeting macrophage polarization, including the critical roles of non-coding RNA and exosomes in regulating this process. The polarization state of macrophages is highlighted as a key determinant in PCa progression, offering a novel perspective for clinical treatment. Future research should concentrate on gaining a deeper understanding of the molecular mechanisms underlying macrophage polarization and on developing effective targeted therapeutic strategies. The exploration of the potential of combination therapies to improve treatment efficacy is also emphasized. By emphasizing the importance of macrophages as a therapeutic target in PCa, this review aims to provide valuable insights and research directions for clinicians and researchers.


Assuntos
Macrófagos , Neoplasias da Próstata , Microambiente Tumoral , Humanos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/imunologia , Masculino , Animais , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo , Progressão da Doença , Citocinas/metabolismo
4.
Colloids Surf B Biointerfaces ; 241: 113992, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38833960

RESUMO

In order to reduce the cardiotoxicity of doxorubicin (DOX) and improve its antitumor effect, dihydroartemisinin (DHA) and DOX prodrug (DOX-S-DHA) synthesized via a single sulfur bond was used with TEPP-46 to prepare nano-liposomes (DOX-S-DHA@TEPP-46 Lips). In which, TEPP-46 was expected to exert p53 bidirectional regulation to promote the synergistic antitumor effect of DOX and DHA while reducing cardiotoxicity. DOX-S-DHA@TEPP-46 Lips exhibited uniform particle size, good stability, and excellent redox-responsive activity. DOX-S-DHA@TEPP-46 Lips could significantly inhibit the proliferation of tumor cells, but had less cytotoxicity on normal cells. The presence of TEPP-46 increased the content of p53 protein, which further induced tumor cell apoptosis. DOX-S-DHA@TEPP-46 Lips had satisfactory long circulation to enhance the antitumor efficacy and reversed the cardiotoxicity of DOX in B16-F10 tumor-bearing mice. In conclusion, DOX-S-DHA@TEPP-46 Lips provides a new insight on creating sophisticated redox-sensitive nano-liposomes for cancer therapy as well as the decreased cardiotoxicity of DOX.


Assuntos
Artemisininas , Cardiotoxicidade , Doxorrubicina , Lipossomos , Pró-Fármacos , Animais , Artemisininas/química , Artemisininas/farmacologia , Artemisininas/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Camundongos , Lipossomos/química , Cardiotoxicidade/prevenção & controle , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Tamanho da Partícula , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Camundongos Endogâmicos C57BL , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Linhagem Celular Tumoral
5.
J Ethnopharmacol ; 331: 118293, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38705430

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.


Assuntos
Apoptose , Pontos de Checagem do Ciclo Celular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição STAT3 , Humanos , Fator de Transcrição STAT3/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Hep G2 , Medicamentos de Ervas Chinesas/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
6.
Gut Microbes ; 16(1): 2327377, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38466137

RESUMO

Although metals are essential for life, they are toxic to bacteria in excessive amounts. Therefore, the maintenance of metal homeostasis is critical for bacterial physiology and pathogenesis. Vibrio parahaemolyticus is a significant food-borne pathogen that mainly causes acute gastroenteritis in humans and acute hepatopancreatic necrosis disease in shrimp. Herein, we report that ZntA functions as a zinc (Zn) and cadmium (Cd) homeostasis mechanism and contributes to oxidative stress resistance and virulence in V. parahaemolyticus. zntA is remarkably induced by Zn, copper, cobalt, nickel (Ni), and Cd, while ZntA promotes V. parahaemolyticus growth under excess Zn/Ni and Cd conditions via maintaining Zn and Cd homeostasis, respectively. The growth of ΔzntA was inhibited under iron (Fe)-restricted conditions, and the inhibition was associated with Zn homeostasis disturbance. Ferrous iron supplementation improved the growth of ΔzntA under excess Zn, Ni or Cd conditions. The resistance of ΔzntA to H2O2-induced oxidative stress also decreased, and its virulence was attenuated in zebrafish models. Quantitative real-time PCR, mutagenesis, and ß-galactosidase activity assays revealed that ZntR positively regulates zntA expression by binding to its promoter. Collectively, the ZntR-regulated ZntA is crucial for Zn and Cd homeostasis and contributes to oxidative stress resistance and virulence in V. parahaemolyticus.


Assuntos
Microbioma Gastrointestinal , Vibrio parahaemolyticus , Humanos , Animais , Zinco , Cádmio/toxicidade , Vibrio parahaemolyticus/genética , Virulência , Peróxido de Hidrogênio , Peixe-Zebra , Homeostase , Estresse Oxidativo , Ferro
7.
Biomaterials ; 305: 122456, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38184961

RESUMO

Combination therapy based on sonodynamic therapy (SDT) combined with immune checkpoint blockers anti-PD-L1 provides effective anti-tumor effects. We designed a combination therapy based on M1/PLGA@IR780/CAT NPs of SDT-enhanced immunity combined with immune checkpoint blockers against PD-L1, which was based on M1 macrophage membrane-encapsulated poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with the acoustic sensitizer IR780 and catalase (CAT) to successfully realize it. SDT based on M1/PLGA@IR780/CAT NPs could induce tumor cell death by promoting dendritic cell (DC) maturation and modulating the tumor immune microenvironment. In particular, the systemic anti-tumor immune response and potent immune memory induced upon combination with anti-PD-L1 checkpoint blockade not only alleviated the progression of mammary cancer in 4T1 mice and effectively blocked distant metastasis, but also prevented tumor recurrence, providing a promising new therapeutic strategy for clinical tumor therapy.


Assuntos
Inibidores de Checkpoint Imunológico , Nanopartículas , Animais , Camundongos , Biomimética , Recidiva Local de Neoplasia , Imunoterapia , Macrófagos , Linhagem Celular Tumoral , Microambiente Tumoral
8.
Eur J Pharmacol ; 966: 176333, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38278466

RESUMO

The µ-opioid receptor-biased agonist theory holds that Gio protein signaling mediates the analgesic effect of opioids and the related side effects via the ß-arrestin2 signaling pathway. A series of µ-opioid-biased agonists have been developed in accordance with this theory, and the FDA has approved TRV130 (as a representative of biased agonists) for marketing. However, several reports have raised the issue of opioid side effects associated with the use of agonists. In this study, five permeable peptides were designed to emulate 11 S/T phosphorylation sites at the µ-opioid receptor (MOR) carboxyl-terminal. In vitro experiments were performed to detect the activation level of G proteins from the cAMP inhibition assay and the ß-arrestin2 recruitment by the BRET assay. Designed peptides might effectively interfere with the activation of the Gio and ß-arrestin2 pathways when combined with morphine. The resulting morphine-induced tolerance, respiratory inhibition, and constipation in mice showed that the ß-arrestin2 pathway was responsible for morphine tolerance while the Gio signaling pathway was involved with respiratory depression and constipation and that these side effects were significantly related to phosphorylation sites S363 and T370. This study may provide new directions for the development of safer and more effective opioid analgesics, and the designed peptides may be an effective tool for exploring the mechanism by which µ-opioid receptors function, with the potential of reducing the side effects that are associated with clinical opioid treatment.


Assuntos
Analgésicos Opioides , Morfina , Camundongos , Animais , Morfina/efeitos adversos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/metabolismo , Receptores Opioides mu/metabolismo , Transdução de Sinais , Constipação Intestinal/induzido quimicamente , Peptídeos/metabolismo , beta-Arrestina 2/metabolismo
9.
Thorac Cancer ; 15(2): 142-151, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986711

RESUMO

BACKGROUND: Using the published survival statistics from cancer registration or population-based studies, we aimed to describe the global pattern and trend of lung cancer survival. METHODS: By searching SinoMed, PubMed, Web of Science, EMBASE, and SEER, all survival analyses from cancer registration or population-based studies of lung cancer were collected by the end of November 2022. The survival rates were extracted by sex, period, and country. The observed, relative, and net survival rates of lung cancer were applied to describe the pattern and time changes from the late 1990s to the early 21st century. RESULTS: Age-standardized 5-year relative/net survival rate of lung cancer was typically low, with 10%-20% for most regions. The highest age-standardized relative/net survival rate was observed in Japan (32.9%, 2010-2014), and the lowest was in India (3.7%, 2010-2014). In most countries, the five-year age-standardized relative/net survival rates of lung cancer were higher in females and younger people. The patients with adenocarcinoma had a better prognosis than other groups. In China, the highest 5-year overall relative/net survival rates were 27.90% and 31.62% in men and women in Jiangyin (2012-2013). CONCLUSION: Over the past decades, the prognosis of lung cancer has gradually improved, but significant variations were also observed globally. Worldwide, a better prognosis of lung cancer can be observed in females and younger patients. It is essential to compare and evaluate the histological or stage-specific survival rates of lung cancer between different regions in the future.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Neoplasias Pulmonares/epidemiologia , Taxa de Sobrevida , Adenocarcinoma/patologia , Prognóstico , Análise de Sobrevida , Incidência
10.
Infect Drug Resist ; 16: 7455-7464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089959

RESUMO

Background: The COVID-19 pandemic presents challenges for healthcare systems globally, especially in vulnerable populations such as pediatric hematopoietic stem cell transplant (HSCT) recipients. This study examines the clinical characteristics and outcomes of COVID-19 infection in pediatric HSCT recipients within one year post-HSCT. Methods: Retrospective analysis was conducted on data from 247 pediatric patients. None of them had received SARS-CoV-2 vaccination or had prior infection. SARS-CoV-2 infection was confirmed using RT-PCR testing. COVID-19 disease severity was categorized according to established guidelines. Demographic, clinical, laboratory, imaging and treatment data were collected. Results: The median age of the cohort was 7±3.7 years, with thalassemia major as the predominant underlying disease. Allogeneic HSCT was performed in the majority of cases, with haploidentical donors being the most common source of grafts. Nearly half of the patients developed COVID-19, with significantly higher infection rates observed in recipients over 100 days compared to recipients within 100 days post-HSCT (40.1% vs 21.7%, p<0.05, Fisher's Exact test). Fever (n=107, 43.2%) and cough (n=88, 35.6%) were the most common symptoms. While most patients had mild disease and did not require specific anti-viral treatment, a significant proportion required hospitalization (n=34, 13.8%). Various treatments were employed hospitalized patients, including Paxlovid (n=19, 55.9%), methylprednisolone (n=7, 20.6%), IL-6 antibody (n=2, 5.9%), mesenchymal stem cells (n=3, 8.8%), and exosomes nebulization therapy (n=2, 5.9%). Despite multidisciplinary approaches, one patient died from severe respiratory failure. However, overall survival of all patients remained high (99.53%; CI 96.72-99.93%), indicating favorable outcomes in pediatric HSCT recipients with COVID-19. Conclusion: This study provides insights into clinical features, therapeutic measures, and outcomes of pediatric HSCT recipients following COVID-19 infection in a large HSCT center in China. These findings contribute to our understanding of COVID-19 in this population and inform strategies to mitigate the impact the pandemic's impact on their care.

11.
Foods ; 12(24)2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38137315

RESUMO

We aim to improve the product quality of GABA raw Pu-erh tea during development and processing. In this study, headspace solid-phase microextraction gas chromatography-mass spectrometry technology combined with relative odor activity evaluations was used to compare the volatile compounds of GABA sun-dried green tea and GABA raw Pu-erh tea. Sensory evaluation showed a higher aroma score of GABA raw Pu-erh tea than that of GABA sun-dried green tea, with significant differences in aroma type and purity. A total of 147 volatile compounds of 13 categories were detected, which differed in composition and quantity between the two teas. 2-Buten-1-one,1-(2,6,6-trimethyl-1,3-cyclohexadien-1-yl)-,(E)- and beta.-myrcene largely contributed to the aroma formation of both teas. Five volatile compounds were screened as potential markers for tea aroma. Metabolic pathway analysis showed that monoterpenoid biosynthesis may be beneficial to the formation of flowery and fruity aromas in the teas. We suggest that the findings of this study may provide important guidance for the processing and optimization of GABA tea.

12.
J Reprod Immunol ; 160: 104166, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37925864

RESUMO

Sleep deprivation is a common problem during pregnancy, but its impact on the fetus remains unclear. We aimed to investigate the effect of sleep deprivation during pregnancy on fetal outcomes and its mechanism in Sprague-Dawley rats. Sleep deprivation was performed from gestational day(GD) 1-19 using a multiplatform method for 18 h/day. Rats were sacrificed on GD20, and their blood and placentas were collected. Fetal and placental parameters were ascertained. Melatonin, adrenocorticotropic hormone (ACTH) and corticosterone were also measured in serum. The levels of arylalkylamine N-acetyltransferase (AANAT) and two melatonin receptors MT1 and MT2, in placental tissues were detected by western blotting. The inflammatory status and oxidative stress in serum and placentas were investigated. Miscarriage and intrauterine growth restriction were observed in the sleep deprivation group. Sleep deprivation resulted in an increased fetal absorption rate, while fetal weight, crown-rump length and placental weight were reduced. Placental histopathology showed that the labyrinth ratio in the sleep deprivation group was significantly reduced, with hypoplastic villi and obviously decreased blood vessels. Sleep deprivation decreased melatonin in serum and the expression of AANAT, MT1 and MT2 in placental tissues, elevated the oxidative stress products 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde(MDA) in serum and 4-hydroxynonenal (4HNE) in the placenta, and decreased the antioxidants superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in serum. Serum proinflammatory cytokines including interleukin-1-beta (IL-1ß), interleukin-6 (IL-6), necrotizing factor-alpha (TNF-α), and interleukin-8(IL-8), were all elevated by sleep deprivation, and the inflammatory regulatory factor nuclear factor-κB p65 (NF-κB p65) in the placenta was enhanced when examined by immunohistochemistry. Corticosterone levels were comparable between the two groups, although ACTH levels were elevated significantly in the sleep deprivation group. Our study revealed that sleep deprivation during pregnancy can adversely impact fetal outcomes. Melatonin may play an important role in this pathology through the oxido-inflammatory process.


Assuntos
Melatonina , Placenta , Ratos , Gravidez , Feminino , Animais , Ratos Sprague-Dawley , Placenta/metabolismo , Privação do Sono/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Corticosterona/metabolismo , Corticosterona/farmacologia , Interleucina-6/metabolismo , Feto , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia
13.
Radiology ; 309(2): e230949, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37987664

RESUMO

Background Preoperative assessment of follicular thyroid neoplasms is challenging using the current US risk stratification systems (RSSs) that are applicable to papillary thyroid neoplasms. Purpose To develop a US feature-based RSS for differentiating between follicular thyroid adenoma (FTA) and follicular thyroid carcinoma (FTC) in biopsy-proven follicular neoplasm and compare it with existing RSSs. Materials and Methods This retrospective multicenter study included consecutive adult patients who underwent conventional US and received a final diagnosis of follicular thyroid neoplasm from seven centers between January 2018 and December 2022. US images from a pretraining data set were used to improve readers' understanding of the US characteristics of the FTC and FTA. Univariable and multivariable logistic regression analyses were used to assess the association of qualitative US features with FTC in a training data set. Features with P < .05 were used to construct a prediction model (follicular tumor model, referred to as F model) and RSS for follicular neoplasms using the Thyroid Imaging Reporting and Data System (TI-RADS). Area under the receiver operating characteristic curve (AUC) was compared between follicular TI-RADS (hereafter, F-TI-RADS) and existing RSS (American College of Radiology [ACR] TI-RADS, Korean Society of Thyroid Radiology and Korean Society of Radiology TI-RADS [hereafter, referred to as K-TI-RADS], and Chinese TI-RADS [hereafter, referred to as C-TI-RADS]) in a validation data set. Results The pretraining, training, and validation data sets included 30 (mean age, 47.6 years ± 16.0 [SD]; 16 male patients; FTCs, 30 of 60 [50.0%]), 703 (mean age, 47.9 years ± 14.5; 530 female patients; FTCs, 188 of 703 [26.7%]), and 155 (mean age, 49.9 years ± 13.3 [SD]; 155 female patients; FTCs, 43 of 155 [27.7%]) patients. In the validation data set, the F-TI-RADS showed improved performance for differentiating between FTA and FTC (AUC, 0.81; 95% CI: 0.71, 0.86) compared with ACR TI-RADS (AUC, 0.74; 95% CI: 0.66, 0.80; P = .02), K-TI-RADS (AUC, 0.69; 95% CI: 0.61, 0.76; P = .002), and C-TI-RADS (AUC, 0.68; 95% CI: 0.60, 0.75; P = .002). Conclusion F-TI-RADS outperformed existing RSSs for differentiating between FTC and FTA. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Baumgarten in this issue.


Assuntos
Neoplasias da Glândula Tireoide , Adulto , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Projetos de Pesquisa , Medição de Risco
14.
Heliyon ; 9(11): e22501, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034624

RESUMO

The aim of the study was to identify predictive patient characteristics for Henoch Schoenlein Purpura (HSPN) relapse in childhood HSPN. One hundred and thirty-five Chinese children with HSPN were enrolled in this study, mean age 10.25 ± 3.39 years. The pathology of HSPN was according to the International Study of Kidney Disease in Children criteria.(ISKDC); ISKDC II(mesangial proliferation (MP)) AND ISKDC III (MP with <50 % crescents).Recurrence of HSPN was observed in 66.3 % patients; male to female ratio (2:1)Statistically significant correlation existed between biopsy grade(p < 0.001), gender(p < 0.001),age ranges(p = 0.002) and treatment regimen (p < 0.001)in the frequency of recurrent HSPN episodes. We identified some significant predictors for HSPN relapse such as the severity of HSPN, adjunctive therapies administered to these patients,and close attention should be paid in patients between the ages 7 and 12 years old. In addition, the use of mycophenolate mofetil as an adjunctive therapy in the treatment of HSPN may reduce the frequency of HSPN relapse episodes in children.

15.
Adv Clin Exp Med ; 2023 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-37855059

RESUMO

BACKGROUND: The impact of cysteine-rich angiogenic inducer 61 (Cyr61, also called CCN1) on endothelial progenitor cells (EPCs) from diabetic-rat-derived whole peripheral and bone marrow remains poorly understood. Therefore, the expression levels of CCN1, CCN1-induced C-X-C chemokine receptor type 4 (CXCR4), and stromal-cell-derived factor-1 (SDF-1) were explored under high glucose (HG) conditions. OBJECTIVES: The aim of the study was to explore the effects of high CCN1 levels on EPC activity in diabetic rats through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway modulation. MATERIAL AND METHODS: Primary EPCs were isolated from bone marrow and whole peripheral blood of streptozocin (STZ)-induced diabetic Sprague-Dawley rats and controls. Cell migration, tube formation ability and viability were determined using transwell, Cell Counting Kit-8 (CCK-8), and Matrigel®-based capillary-like tube formation assays. Protein and gene expression levels were measured by western blot and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The study findings showed that EPC migration, viability and tube formation ability were significantly lower under HG conditions. High CCN1 expression levels restored EPC function by inducing SDF-1 and CXCR4 in EPCs under HG conditions. Furthermore, HG suppressed MEK/ERK phosphorylation, while an ERK1/2 agonist rescued EPC CCN1-SDF-1/CXCR4 expression under HG conditions through the activation of the MEK/ERK pathway. CONCLUSIONS: This study demonstrates that high CCN1 expression levels restored EPC functions, partly by modulating MEK/ERK signaling. These findings provide a basis for developing novel therapeutic methods for diabetic vascular neogenesis and vascular injury repair.

16.
Open Med (Wars) ; 18(1): 20230800, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37873537

RESUMO

This study aimed to investigate the effect of aquaporin-4 (AQP4) on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts. A model of diffuse ischemic brain injury was established, and adenovirus was injected stereotactically through the lateral ventricle of mice. The water content of the brain tissue was measured. The co-expression of glial fibrillary acidic protein (GFAP) and AQP4 and the aggregation of p-tau and neuronal marker were detected through immunofluorescence double staining. The expression of phosphorylated microtubule-associated protein tau (p-tau, Ser202/Thr205, Thr205, Ser396, Ser404), interleukin(IL)-6, IL-1ß, tumor necrosis factor (TNF)-a, growth associated protein43 (GAP43), GFAP, and ionized calcium-binding adapter molecule 1 (Iba1) was detected through Western blot. It was found that the brain water content in the model group was increased and decreased after the AQP4 interference. Compared with the sham group, the expression of GFAP, p-tau, IL-1ß, TNF-a, Iba1, and p-tau was increased in the model group (p < 0.05). Compared with the model group, the expression of p-tau, IL-6, IL-1ß, TNF-a, GFAP, and Iba1 was decreased after AQP4 interference (p < 0.05). It is indicated that AQP4 positively regulates neurodegeneration and persistent neuroinflammation caused by tau protein aggregation after cerebral microinfarcts.

17.
Int Wound J ; 20(9): 3898-3905, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37293742

RESUMO

A meta-analysis was performed to comprehensively assess the effects of video-assisted thoracoscopy on surgical site wound infection and wound pain in patients with lung cancer. Studies on video-assisted thoracoscopy for lung cancer were collected from PubMed, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang database, from inception to January 2023. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.4 software. Thirty-one articles with a total of 3608 patients were included, with 1809 in the video-assisted thoracoscopy group and 1799 in the control group. Compared with the control group, video-assisted thoracoscopy significantly reduced surgical site wound infection (odds ratio: 0.22, 95% confidence interval [CI]: 0.14-0.33, P < .001) and surgical site wound pain at postoperative day 1 (standardised mean difference [SMD]: -0.90, 95% CI: -1.17 to -0.64, P < .001) and postoperative day 3 (SMD: -1.59, 95% CI: -2.25 to -0.92, P < .001). Thus, these results showed that video-assisted thoracoscopy may have beneficial outcomes by reducing surgical site wound infection and pain. However, owing to the large variation in sample sizes and some methodological shortcomings, further validation is needed in future studies with higher quality and larger sample sizes.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/cirurgia , Infecção da Ferida Cirúrgica/etiologia , Dor , Toracoscopia , China
18.
J Biomater Appl ; 38(1): 134-145, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37276487

RESUMO

The repair and functional reconstruction of large skin defects caused by burn remains an intractable clinical problem. Collagen type I (ColI) was extracted from carp scales and confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis ultraviolet adsorption spectra and automatic amino acid analyzer. Then the scaffolds containing the purified ColI, hyaluronic acid (HA) and chondroitin sulfate (CS) were constructed and examined. The results showed that the scaffold (ColI:CS:HA=9:1:1) had larger pore diameter, porosity, water absorption, degradation rate and tensile strength. gentamycin sulphate (GS) - gelatin microspheres (GMSs) were prepared by emulsion cross-linking method. The drug release study of the ColI-CS-HA-GS/GMSs scaffold with antibacterial property showed a prolonged, continuous, and sustained release of GS. The bone marrow mesenchymal stem cells (BMSCs) were extracted from rat and inoculated into the ColI-HA-CS-GS/GMSs scaffold. The results performed that the scaffold could accelerate proliferation of the BMSCs and wound healing.


Assuntos
Células-Tronco Mesenquimais , Engenharia Tecidual , Ratos , Animais , Engenharia Tecidual/métodos , Ácido Hialurônico/química , Gelatina/química , Alicerces Teciduais/química , Gentamicinas/farmacologia , Gentamicinas/metabolismo , Colágeno/química , Sulfatos de Condroitina/química , Células-Tronco Mesenquimais/metabolismo
19.
Genes Genomics ; 45(7): 855-866, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37133722

RESUMO

BACKGROUND: Non-voltage-gated sodium channel, also known as the epithelial sodium channel (ENaC), formed by heteromeric complexes consisting of SCNN1A, SCNN1B, and SCNN1G, is responsible for maintaining sodium ion and body fluid homeostasis in epithelial cells. However, no systematic study of SCNN1 family members has been conducted in renal clear cell carcinoma (ccRCC) to date. OBJECTIVE: To investigate the abnormal expression of SCNN1 family in ccRCC and its potential correlation with clinical parameters. METHODS: The transcription and protein expression levels of SCNN1 family members in ccRCC were analyzed based on the TCGA database, and were confirmed by quantitative RT-PCR and immunohistochemical staining assays, respectively. The area under curve (AUC) was used to evaluate the diagnostic value of SCNN1 family members for ccRCC patients. RESULTS: The mRNA and protein expression of SCNN1 family members was significantly downregulated in ccRCC compared with normal kidney tissues, which might be due to DNA hypermethylation in the promoter region. It is worth noting that the AUC of SCNN1A, SCNN1B, and SCNN1G were 0.965, 0.979, and 0.988 based on the TCGA database (p < 0.0001), respectively. The diagnostic value was even higher when combing these three members together (AUC = 0.997, p < 0.0001). Intriguingly, the mRNA level of SCNN1A was significantly lower in females compared with males, while SCNN1B and SCNN1G were increased with the progression of ccRCC and remarkably associated with a worse outcome for patients. CONCLUSION: The aberrantly decrease of SCNN1 family members might serve as valuable biomarkers for the diagnosis of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Masculino , Feminino , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Rim/metabolismo , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , RNA Mensageiro/metabolismo
20.
Int J Antimicrob Agents ; 61(5): 106794, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933871

RESUMO

BACKGROUND: Pseudomonas aeruginosa is one of the most common pathogens that lead to fatal human infection. This Gram-negative pathogen has evolved complex drug resistance, which poses significant challenges to the current antibiotic-dependent healthcare system. New therapeutic approaches are urgently required to treat infections caused by P. aeruginosa. METHODS: Inspired by ferroptosis, the antibacterial effects of iron compounds on P. aeruginosa via direct exposure were investigated. In addition, thermal-responsive hydrogels to carry FeCl3 were developed as a wound dressing to treat P. aeruginosa-induced wound infection in a mouse model. RESULTS: The results showed that 200 µM FeCl3 killed more than 99.9% of P. aeruginosa cells. FeCl3-mediated cell death in P. aeruginosa was associated with hallmarks of ferroptosis in mammalian cells, including reactive oxygen species (ROS) burst, lipid peroxidation, and DNA damage. Catalase or Fe2+ chelator alleviated FeCl3-mediated cell death, indicating that H2O2 and labile Fe2+ induced the Fenton reaction leading to cell death. Further proteomics analysis showed that proteins related to glutathione (GSH) synthesis and the glutathione peroxidase (GPX) family were significantly downregulated after FeCl3 treatment, which is equivalent to GPX4 inactivation in mammalian cells. The therapeutic effect of FeCl3 on P. aeruginosa was further evaluated in a mouse wound infection model using polyvinyl alcohol-boric acid (PB) hydrogels as a carrier of FeCl3. FeCl3-PB hydrogels completely cleared pus on wounds and promoted wound healing. CONCLUSION: These results indicated that FeCl3 induces microbial ferroptosis in P. aeruginosa and has high therapeutic potential for the treatment of P. aeruginosa wound infection.


Assuntos
Ferroptose , Infecção dos Ferimentos , Camundongos , Animais , Humanos , Pseudomonas aeruginosa , Peróxido de Hidrogênio/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Cicatrização , Glutationa/farmacologia , Hidrogéis/farmacologia , Mamíferos
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