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1.
iScience ; 27(4): 109567, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617561

RESUMO

The human respiratory system is a complex and important system that can suffer a variety of diseases. Single-cell sequencing technologies, applied in many respiratory disease studies, have enhanced our ability in characterizing molecular and phenotypic features at a single-cell resolution. The exponentially increasing data from these studies have consequently led to difficulties in data sharing and analysis. Here, we present scMoresDB, a single-cell multi-omics database platform with extensive omics types tailored for human respiratory diseases. scMoresDB re-analyzes single-cell multi-omics datasets, providing a user-friendly interface with cross-omics search capabilities, interactive visualizations, and analytical tools for comprehensive data sharing and integrative analysis. Our example applications highlight the potential significance of BSG receptor in SARS-CoV-2 infection as well as the involvement of HHIP and TGFB2 in the development and progression of chronic obstructive pulmonary disease. scMoresDB significantly increases accessibility and utility of single-cell data relevant to human respiratory system and associated diseases.

2.
Injury ; : 111482, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38461103

RESUMO

BACKGROUND: This study aimed to assess the clinical epidemiological characteristics of children with electrical injuries and discuss the countermeasures for the prevention of electrical injuries in children. METHODS: The children with electrical injuries were grouped according to whether or not they were admitted to the hospital for treatment into inpatient and outpatient groups. Clinical data such as gender, causes of injury and injury-causing voltage distribution in different age groups were analyzed. The factors affecting hospitalization were subjected to χ2 test, Kruskal-Wallis H test, and logistic regression analysis. RESULTS: A total of 321 children were included with 37 divided into inpatient group and 284 divided into outpatient group. The incidence of electrical injuries was highest in children ≤6 years old and in the summer. There were significantly different in gender, place of occurrence, cause of injury and injury-causing voltage between the two groups (p < 0.05). Injury-causing voltage is an independent risk factor affecting hospitalization of children with electrical injuries (OR = 0.116, 95 %CI = 0.040-0.334, p = 0.000). In children ≤6 years old, boys suffered electrical injuries more frequently than girls; battery powered vehicle (47.53 %) was primarily the cause of injury; most of the patients (64.64 %) were exposed to low voltage below 100 Vs, mainly in the case of adolescent children. CONCLUSION: Male preschoolers accounted for the majority of electrical injury cases, and these accidents mostly happened in household electrical appliances and household battery cars. Overall, it is necessary to improve family electrical safety education and reinforce protective measures against electric injury to children.

3.
Pediatr Investig ; 8(1): 21-26, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38516144

RESUMO

Importance: Necrotizing soft tissue infection (NSTI) is a serious infectious disease. However, the early clinical manifestations and indicators of NSTI in children are still unclear. Objective: The purpose of this study was to analyze the clinical characteristics and risk factors of NSTI in pediatric patients. Methods: A total of 127 children with skin and soft tissue infection (SSTI) were treated at our hospital and divided into two groups: the NSTI group and the non-NSTI group, based on their discharge diagnosis from January 2011 to December 2022. Then, we collected and analyzed the clinical characteristics and risk factors of all patients, including sex and age, disease inducement, admission temperature, local skin manifestations, infection site, the presence of sepsis, bacterial culture, and laboratory indicators. Results: In our study, there was a statistical difference in the age distribution and disease inducement between NSTI and non-NSTI groups. The occurrence of local skin manifestations (blisters/bullae and ecchymosis) and the presence of sepsis significantly increased in the NSTI group compared to the non-NSTI group. Additionally, only the platelet count on laboratory tests was statistically different between the NSTI and non-NSTI groups. Finally, the logistic regression analysis suggested that local skin manifestations such as blisters/bullae, and ecchymosis, as well as the presence of sepsis, were identified as risk factors for NSTI. Interpretation: Children with SSTI and skin manifestations such as blisters/bullae, ecchymosis, and the presence of sepsis are at a higher risk of developing NSTI. These symptoms serve as useful indicators for early detection of NSTI.

4.
Front Pharmacol ; 15: 1365802, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523633

RESUMO

Arachidonic acid (AA) is a main component of cell membrane lipids. AA is mainly metabolized by three enzymes: cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). Esterified AA is hydrolysed by phospholipase A2 into a free form that is further metabolized by COX, LOX and CYP450 to a wide range of bioactive mediators, including prostaglandins, lipoxins, thromboxanes, leukotrienes, hydroxyeicosatetraenoic acids and epoxyeicosatrienoic acids. Increased mitochondrial oxidative stress is considered to be a central mechanism in the pathophysiology of the kidney. Along with increased oxidative stress, apoptosis, inflammation and tissue fibrosis drive the progressive loss of kidney function, affecting the glomerular filtration barrier and the tubulointerstitium. Recent studies have shown that AA and its active derivative eicosanoids play important roles in the regulation of physiological kidney function and the pathogenesis of kidney disease. These factors are potentially novel biomarkers, especially in the context of their involvement in inflammatory processes and oxidative stress. In this review, we introduce the three main metabolic pathways of AA and discuss the molecular mechanisms by which these pathways affect the progression of acute kidney injury (AKI), diabetic nephropathy (DN) and renal cell carcinoma (RCC). This review may provide new therapeutic targets for the identification of AKI to CKD continuum.

5.
Aesthetic Plast Surg ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443745

RESUMO

BACKGROUND: This study investigated the trends, motivations and preferences of rhinoplasty in China. METHODS: Data on rhinoplasty were collected from Xiaohongshu and analyzed for trends. Text analysis and word frequency statistics were performed on the notes and comments using Python modules. RESULTS: We obtained 1065 notes with 102,153 comments, 239,383 collections and 640,579 likes. The number of rhinoplasty-related publications increased annually, correlating with per capita disposable income of households (DI) growth (r2 = 0.609, P = 0.041 < 0.05). In the Southern provinces, there was a notably higher volume of publications compared to the Northern provinces (P = 0.001). Furthermore, a significant correlation was observed between publication data, population size, and the DI (r2 = 0.786, P < 0.001). The nasal tip (3197) and nasion (1409) were the most mentioned nasal subunits. "Good-looking" (9672) and "natural" (2811) were the most used words to describe the nose shape. The "doctor" (4377), the "hospital" (2182) and "hyaluronic acid" (2106) were the most mentioned rhinoplasty procedure related vocabulary. CONCLUSIONS: Discussions about rhinoplasty in China are increasing, and more people express their desire for rhinoplasty on social networks, related to China's DI growth. The Southern provinces show a higher inclination toward these discussions, a trend that correlates with our findings of a positive association between NOPs and both DI and population size. Netizens pay more attention to the shape of nasal tip and nasion, and prefer the good-looking and natural appearance. Most people consider autologous cartilage or hyaluronic acid injection for rhinoplasty. Doctors are the primary consideration for patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

6.
J Immunother Cancer ; 12(2)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302415

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved patient survival in multiple cancers. However, therapy response in esophageal cancer is limited to subgroups of patients and clinically useful predictive biomarkers are lacking. METHODS: We collected a series of plasma samples from 91 patients with esophageal cancer before and after ICI treatment. The Olink Immuno-Oncology panel (92 proteins) with proximity extension assays was used to detect the dynamic changes in plasma and potential biomarkers associated with treatment outcomes. We screened all survival-related proteins and established a risk score model to better predict the prognosis and treatment response in patients with esophageal cancer immunotherapy. RESULTS: We found that 47 out of 92 quantified proteins had significant changes in plasma levels during ICI treatment (p<0.050), and these changed proteins were involved in immune-related reactions, such as intercellular adhesion and T-cell activation. Notably, the baseline levels of three angiogenesis-related proteins (IL-8, TIE2, and HGF) were significantly associated with the survival outcomes of patients treated with ICIs (p<0.050). According to these prognostic proteins, we established an angiogenesis-related risk score, which could be a superior biomarker for ICI response prediction. In addition, antiangiogenic therapy combined with ICIs significantly improved overall survival compared with ICI monotherapy (p=0.044). CONCLUSIONS: An angiogenesis-related risk score based on three proteins (IL-8, TIE2, and HGF) could predict ICI response and prognosis in patients with esophageal cancer, which warrants verification in the future. Our study highlights the potential application of combining ICIs and antiangiogenic therapy and supports Olink plasma protein sequencing as a liquid biopsy method for biomarker exploration.


Assuntos
60489 , Neoplasias Esofágicas , Humanos , Prognóstico , Interleucina-8 , Proteínas Sanguíneas , Imunoterapia , Neoplasias Esofágicas/tratamento farmacológico , Proteínas Angiogênicas , Biomarcadores
7.
Immun Inflamm Dis ; 12(2): e1140, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38415918

RESUMO

BACKGROUND: Inflammatory response of central nervous system is an important component mechanism in the bladder pain of interstitial cystitis/bladder pain syndrome (IC/BPS). Exosomes transfer with microRNAs (miRNA) from mesenchymal stem cell (MSCs) might inhibit inflammatory injury of the central nervous system. Herein, the purpose of our study was to explore the therapeutic effects by which extracellular vesicles (EVs) derived from miR-9-edreched MSCs in IC/BPS and further investigate the potential mechanism to attenuate neuroinflammation. METHODS: On the basis of IC/BPS model, we used various techniques including bioinformatics, cell and molecular biology, and experimental zoology, to elucidate the role and molecular mechanism of TLR4 in regulating the activation of NLRP3 inflammasome in bladder pain of IC/BPS, and investigate the mechanism and feasibility of MSC-EVs enriched with miR-9 in the treatment of bladder pain of IC/BPS. RESULTS: The inflammatory responses in systemic and central derived by TLR4 activation were closely related to the cystitis-induced pelvic/bladder nociception in IC/BPS model. Intrathecal injection of miR-9-enreched MSCs derived exosomes were effective in the treatment of cystitis-induced pelvic/bladder nociception by inhibiting TLR4/NF-κb/NLRP3 signal pathway in central nervous system of IC/BPS mice. CONCLUSIONS: This study demonstrated that miR-9-enreched MSCs derived exosomes alleviate neuroinflammaiton and cystitis-induced bladder pain by inhibiting TLR4/NF-κb/NLRP3 signal pathway in interstitial cystitis mice, which is a promising strategy against cystitis-induced bladder pain.


Assuntos
Cistite Intersticial , Cistite , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Animais , Camundongos , Cistite Intersticial/terapia , Receptor 4 Toll-Like/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , NF-kappa B , Bexiga Urinária , MicroRNAs/genética , Dor
8.
Burns ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38402118

RESUMO

OBJECTIVE: Electrical burn injuries (EBIs) represent an important subset of burn injuries, but the information on them from the global level is limited. We aimed to investigate the characteristics and risk factors for EBIs reported to the World Health Organization Global Burn Registry. METHODS: Patients with EBIs and non-EBIs were identified from the registry. Patient demographics, income of the country, setting of the injury occurred, and outcomes were described and compared. Multivariable analysis was performed to identify risk factors associated with the EBIs and their outcomes. RESULTS: Of the 9276 patients, 814 (8.8%) were grouped as EBIs. EBIs patients had a median age of 28 years, and they were predominantly males (89.2%). EBIs were more likely to occur in lower-middle- and low-income countries (60.9% versus 43.4%) and in an occupational setting (49.1% versus 6.7%) than the non-EBIs. Older age, male, lower-income, and occupational and public setting were risk factors for EBIs. For EBIs patients, adolescents and young adults, those from low-middle and low-income countries, and those injured by high-voltage electricity were more likely to have more than 15% of the total body surface area. In addition, those from low-middle and low-income countries and those injured by high-voltage electricity were more likely to die. CONCLUSION: The characteristics of EBIs are significantly different from that of non-EBIs. To prevent EBIs and avoid unpleasant outcomes, particular attention should be given to adolescent boys and young adult men who are employed in electrical jobs in lower-income countries.

9.
World Neurosurg ; 183: e818-e824, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38218442

RESUMO

BACKGROUND: The accurate diagnosis of fresh vertebral fractures (VFs) was critical to optimizing treatment outcomes. Existing studies, however, demonstrated insufficient accuracy, sensitivity, and specificity in detecting fresh fractures using magnetic resonance imaging (MRI), and fall short in localizing the fracture sites. METHODS: This prospective study comprised 716 patients with fresh VFs. We obtained 849 Short TI Inversion Recovery (STIR) image slices for training and validation of the AI model. The AI models employed were yolov7 and resnet50, to detect fresh VFs. RESULTS: The AI model demonstrated a diagnostic accuracy of 97.6% for fresh VFs, with a sensitivity of 98% and a specificity of 97%. The performance of the model displayed a high degree of consistency when compared to the evaluations by spine surgeons. In the external testing dataset, the model exhibited a classification accuracy of 92.4%, a sensitivity of 93%, and a specificity of 92%. CONCLUSIONS: Our findings highlighted the potential of AI in diagnosing fresh VFs, offering an accurate and efficient way to aid physicians with diagnosis and treatment decisions.


Assuntos
Aprendizado Profundo , Fraturas da Coluna Vertebral , Humanos , Estudos Prospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Imageamento por Ressonância Magnética/métodos , Coluna Vertebral/patologia , Estudos Retrospectivos
11.
Acta Pharmacol Sin ; 45(1): 137-149, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37640899

RESUMO

Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and ß-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and ß-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of ß-catenin and its downstream gene products, including Snail1 and Twist; treatment with a ß-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream ß-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/ß-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.


Assuntos
Nefropatias , Podócitos , Humanos , Ratos , Animais , beta Catenina/metabolismo , Podócitos/metabolismo , Sirtuína 1/metabolismo , Sistema Renina-Angiotensina , Nefropatias/metabolismo , Proteinúria
12.
Neurosci Lett ; 821: 137608, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38142926

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder with a lack of effective treatment options. mangiferin, a bioactive compound derived from mango, has been shown to possess strong neuroprotective properties. In this study, we investigated the neuroprotective effects of mangiferin on PD and its underlying mechanisms using both in vitro and in vivo models of 6-OHDA-induced PD. Additionally, we conducted molecular docking experiments to evaluate the interaction between mangiferin and AKR1C3 and ß-catenin. Our results demonstrated that treatment with mangiferin significantly attenuated 6-OHDA-induced cell damage in PC12 cells, reducing intracellular oxidative stress, improving mitochondrial membrane potential, and restoring the expression of tyrosine hydroxylase (TH), a characteristic protein of dopaminergic neurons. Furthermore, mangiferin reduced the accumulation of α-synuclein and inhibited the expression of AKR1C3, thereby activating the Wnt/ß-catenin signaling pathway. In vivo studies revealed that mangiferin improved motor dysfunction in 6-OHDA-induced PD mice. Molecular docking analysis confirmed the interaction between mangiferin and AKR1C3 and ß-catenin. These findings indicate that mangiferin exerts significant neuroprotective effects in 6-OHDA-induced PD by inhibiting AKR1C3 and activating the Wnt/ß-catenin signaling pathway. Therefore, mangiferin may emerge as an innovative therapeutic strategy in the comprehensive treatment regimen of PD patients, providing them with better clinical outcomes and quality of life.


Assuntos
Membro C3 da Família 1 de alfa-Ceto Redutase , Fármacos Neuroprotetores , Doença de Parkinson , Xantonas , Animais , Camundongos , Ratos , Membro C3 da Família 1 de alfa-Ceto Redutase/antagonistas & inibidores , beta Catenina/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Oxidopamina/farmacologia , Doença de Parkinson/tratamento farmacológico , Qualidade de Vida , Via de Sinalização Wnt , Xantonas/farmacologia , Xantonas/uso terapêutico , Camundongos Endogâmicos C57BL , Masculino , Células PC12
13.
Br J Pharmacol ; 181(1): 162-179, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37594378

RESUMO

BACKGROUND AND PURPOSE: Membranous nephropathy (MN) is an immune-mediated glomerular disease in adults. Antibody- and antigen-bonding mechanisms have been largely clarified, but the subepithelium immune complex deposition-mediated downstream molecular mechanisms are currently unresolved. Increasing evidence has suggested that gut microbiota contribute to MN pathogenesis. EXPERIMENTAL APPROACH: In this study, we identified alterations in faecal gut microbiota and serum metabolites that mediate an aryl hydrocarbon receptor (AhR) mechanism in cationic bovine serum albumin (CBSA)-induced MN rats and in patients with idiopathic MN (IMN). KEY RESULTS: Impaired renal function correlated with the relative abundance of reduced faecal probiotics, Lactobacillus and Bifidobacterium, and altered serum levels of tryptophan-produced indole derivatives (TPIDs) in MN rats. Further results showed that reduced relative abundance of five probiotics, namely Lactobacillus johnsonii, Lactobacillus murinus, Lactobacillus vaginalis, Lactobacillus reuteri and Bifidobacterium animalis, positively correlated with decreased levels of indole-3-pyruvic acid, indole-3-aldehyde and tryptamine and negatively correlated with increased levels of indole-3-lactic acid and indole-3-acetic acid in serum of MN rats. Altered five probiotics and five TPIDs also were observed in patients with IMN. Further studies showed that MN rats exhibited a significant increase in intrarenal mRNA expression of AhR and its target genes CYP1A1, CYP1A2 and CYP1B1, which were accompanied by protein expression of down-regulated cytoplasmic AhR, but up-regulated nuclear AhR, in MN rats and IMN patients. CONCLUSION AND IMPLICATIONS: Activation of the intrarenal AhR signalling pathway may involve five TPIDs. These data suggest that gut microbiota could influence MN through TPIDs that engage host receptors.


Assuntos
Microbioma Gastrointestinal , Glomerulonefrite Membranosa , Indóis , Lactobacillus , Receptores de Hidrocarboneto Arílico , Lactobacillus/fisiologia , Glomerulonefrite Membranosa/microbiologia , Triptofano/farmacologia , Indóis/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Humanos , Animais , Ratos , Masculino , Ratos Sprague-Dawley , Transdução de Sinais
14.
Altern Ther Health Med ; 29(8): 733-737, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708543

RESUMO

Objective: This study aimed to investigate the clinical features of angioimmunoblastic T-cell lymphoma (AITL) mimicking systemic lupus erythematosus (SLE) and raise awareness about AITL among rheumatologists in order to prevent misdiagnosis and missed diagnosis. The study reports on a case of AITL mimicking SLE and provides a literature review. Methods: Using key words as search terms, relevant articles published in PubMed before 2022-05 were searched, and their clinical characteristics were collected and analyzed. Results: The literature review retrieved six case reports, including four cases initially diagnosed with SLE and then with AITL. The other two case diagnoses were SLE and AITL, respectively. The two diseases are pathogenically associated and share some common features. The clinical manifestations of AITL are complex. The disease is closely associated with abnormal immune functions and is highly heterogeneous. Conclusion: Patients with AITL generally have a poor prognosis. Rarely do reported cases show AITL mimicking SLE. AITL should be considered during clinical practice to prevent missed diagnoses or misdiagnoses.


Assuntos
Linfadenopatia Imunoblástica , Lúpus Eritematoso Sistêmico , Linfoma de Células T , Humanos , Linfadenopatia Imunoblástica/diagnóstico , Linfadenopatia Imunoblástica/complicações , Linfadenopatia Imunoblástica/patologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Linfoma de Células T/diagnóstico , Linfoma de Células T/complicações , Linfoma de Células T/patologia
15.
Psychiatry Res ; 328: 115476, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37708804

RESUMO

Executive functions(EFs) may be associated with the emergence of non-suicidal self-injury(NSSI) due to their role as behavior controllers. EFs includes three core cognitive processes: inhibitory control, working memory, and cognitive flexibility(i.e. the ability to selectively alter cognitive strategies to generate appropriate behavior in the changing environment). This study aimed to systematically explore the three core EFs in depressed adolescents with NSSI. The data was obtained from the baseline data of the Chinese adolescent depression Cohort. The adolescents underwent cognitive assessments to yield domain-specific scores in EFs using the Digit Span Backward test(DSB), the Stroop Color-word interference test- color-word condition(Stroop-CW), and the Wisconsin Card Sorting tests(WCST). The significant differences in WCST scores were found between the NSSI group and the non-NSSI group. NSSI frequency was moderately positively correlated with total errors and negatively correlated with the number of categories completed. The number of categories completed in the "≥200″ NSSI frequency group was significantly lower than that in the "≤10″ NSSI group. The current findings suggested that depressed adolescents who had engaged in NSSI have poorer cognitive flexibility performance compared to adolescents without NSSI. As the frequency of NSSI increased, cognitive flexibility might become worse. These results provide evidence of a connection between executive dysfunctions and NSSI in depressed adolescents.

16.
Inflammation ; 46(6): 2276-2288, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37606850

RESUMO

Acute lung injury (ALI) is a life-threatening disorder stemmed mainly from an uncontrolled inflammatory response. Lipopolysaccharide (LPS) is commonly used to induce ALI animal models. Toll-like receptor 4 (TLR4) is the main receptor for LPS, and myeloid differentiation factor 88 (MyD88) is a key adaptor protein molecule in the Toll-like receptor (TLR) signaling pathway. Thus, MyD88 knockdown heterozygous mice (MyD88+/-) were used to investigate the effect of incomplete knockout of the MyD88 gene on indirect LPS-induced ALI through intraperitoneal injection of LPS. The LPS-induced ALI significantly upregulated MyD88 expression, and heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) ameliorated LPS-induced histopathological injury and collagen fiber deposition. Heterozygous mice with incomplete knockout of the MyD88 gene (MyD88+/-) inhibited LPS-induced nuclear factor-κB (NF-κB) pathway activation, but TLR-4 expression tended to be upregulated. Incomplete knockdown of the MyD88 gene also downregulated LPS-induced expression of IL1-ß, IL-6, TNF-α, TGF-ß, SMAD2, and α-SMA. The transcriptome sequencing also revealed significant changes in LPS-regulated genes (such as IL-17 signaling pathway genes) after the incomplete knockdown of MyD88. In conclusion, this paper clarified that LPS activates the downstream NF-κB pathway depending on the MyD88 signaling pathway, which induces the secretion of inflammatory cytokines such as IL-1ß/IL-6/TNF-α and ultimately triggers ALI. Incomplete knockdown of the MyD88 reverses LPS-induced lung fibrosis, which confirmed the vital role of MyD88 in LPS-induced ALI.


Assuntos
Lesão Pulmonar Aguda , Fibrose Pulmonar , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/metabolismo , Modelos Animais de Doenças , Interleucina-6/metabolismo , Lipopolissacarídeos/efeitos adversos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/prevenção & controle , Fator de Necrose Tumoral alfa/metabolismo
17.
Curr Med Sci ; 43(5): 998-1004, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37558867

RESUMO

OBJECTIVE: Non-suicidal self-injury (NSSI) has a higher prevalence in adolescents with depressive disorders than in community adolescents. This study examined the differences in NSSI behaviors between adolescents with unipolar depression (UD) and those with bipolar depression (BD). METHODS: Adolescents with UD or BD were recruited from 20 general or psychiatric hospitals across China. The methods, frequency, and function of NSSI were assessed by Functional Assessment of Self-Mutilation. The Beck Suicide Ideation Scale was used to evaluate adolescents' suicidal ideation, and the 10-item Kessler Psychological Distress Scale to estimate the anxiety and depression symptoms. RESULTS: The UD group had higher levels of depression (19.16 vs.17.37, F=15.23, P<0.001) and anxiety symptoms (17.73 vs.16.70, F=5.00, P=0.026) than the BD group. Adolescents with BD had a longer course of NSSI than those with UD (2.00 vs.1.00 year, Z=-3.39, P=0.001). There were no statistical differences in the frequency and the number of methods of NSSI between the UD and BD groups. Depression (r=0.408, P<0.01) and anxiety (r=0.391, P<0.01) were significantly and positively related to NSSI frequency. CONCLUSION: Adolescents with BD had a longer course of NSSI than those with UD. More importantly, NSSI frequency were positively and strongly correlated with depression and anxiety symptoms, indicating the importance of adequate treatment of depression and anxiety in preventing and intervening adolescents' NSSI behaviors.

18.
J Environ Manage ; 345: 118629, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37499417

RESUMO

Equipped with hierarchical pores and three-dimensional (3D) center-radial channels, dendritic mesoporous nanoparticles (DMNs) make their pore volumes extremely large, specific surface areas super-high, internal spaces especially accessible, and so on. Other entities (like organic moieties or nanoparticles) can be modified onto the interfaces or skeletons of DMNs, accomplishing their functionalization for desirable applications. This comprehensive review emphasizes on the design and construction of DMNs-based systems which serve as sensors, adsorbents and catalysts for the detection, adsorption, and degradation of hazardous substances, mainly including the construction procedures of brand-new DMNs-based materials and the involved hazardous substances (like industrial chemicals, chemical dyes, heavy metal ions, medicines, pesticides, and harmful gases). The sensitive, adsorptive, or catalytic performances of various DMNs have been compared; correspondingly, the reaction mechanisms have been revealed strictly. It is honestly anticipated that the profound discussion could offer scientists certain enlightenment to design novel DMNs-based systems towards the detection, adsorption, and degradation of hazardous substances, respectively or comprehensively.


Assuntos
Metais Pesados , Nanopartículas , Substâncias Perigosas , Adsorção , Porosidade , Nanopartículas/química
19.
Front Bioeng Biotechnol ; 11: 1225925, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37456721

RESUMO

Background: The effects of cannulated screws made of polyetheretherketone (PEEK) on the biomechanical properties of the vertebral body during vertebra-pediculoplasty remain unclear. This study aimed to investigate whether PEEK screws have the potential to replace titanium alloy screws. Methods: The surgical model of two different materials of screws was constructed using the finite element method. The biomechanical effects of the two models on the vertebral body under different working conditions were compared. Results: ① The peak von Mises stress of PEEK screws was significantly lower than that of titanium screws, with a reduction ranging from 52% to 80%. ② The von Mises stress values for the injured T12 spine were similar for both materials. Additionally, the segmental range of motion and intervertebral disc pressure showed no significant difference between the two materials. Conclusion: PEEK screws demonstrated advantages over titanium screws and may serve as a viable alternative for screw materials in vertebra-pediculoplasty.

20.
Free Radic Biol Med ; 207: 89-106, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37451370

RESUMO

Membranous nephropathy (MN) patients are diagnosed by the presence of phospholipase A2 receptor (PLA2R) before they progress to renal failure. However, the subepithelium-like immunocomplex deposit-mediated downstream molecular pathways are poorly understood. The aryl hydrocarbon receptor (AHR), NF-ƙB and Nrf2 pathways play central roles in the pathogenesis and progression of chronic kidney disease. However, their mutual effects on MN require further examination. Thus, we investigated the effect of AHR signalling on the NF-ƙB and Nrf2 pathways in IMN patients, cationic bovine serum albumin (CBSA)-injected rats and zymosan activation serum (ZAS)-treated podocytes. IMN patients show significantly decreased serum total protein and albumin levels, increased urine protein levels and intrarenal IgG4 and PLA2R protein expression in glomeruli compared with controls. IMN patients exhibited increased mRNA expression of intrarenal AHR and its target genes, including CYP1A1, CYP1A2, CYP1B1 and COX-2. This increase was accompanied by significantly upregulated protein expression of CD3, NF-ƙB p65 and COX-2 and significantly downregulated Nrf2 and HO-1 expression. Similarly, CBSA-induced rats showed severe proteinuria and activated intrarenal AHR signalling. This was accompanied by significantly upregulated protein expression of intrarenal p-IκBα, NF-κB p65 and its gene products, including COX-2, MCP-1, iNOS, 12-LOX, p47phox and p67phox, and significantly downregulated protein expression of Nrf2 and its gene products, including HO-1, catalase, GCLC, GCLM, MnSOD and NQO1. These results were further verified in ZAS-induced podocytes. Treatment with the AHR antagonist CH223191 and AHRsiRNA significantly preserved podocyte-specific protein expression and improved the NF-ƙB and Nrf2 pathways in ZAS-induced podocytes. In contrast, similar results were obtained in ZAS-induced podocytes treated with the NF-ƙB inhibitor BAY 11-7082 and NF-κBp65 siRNA. However, neither method had a significant effect on AHR signalling. Collectively, these results indicate that the NF-ƙB pathway is a downstream target of AHR signalling. Our findings suggest that blocking AHR signalling inhibits oxidative stress and inflammation, thereby improving proteinuria and renal injury.


Assuntos
Glomerulonefrite Membranosa , Animais , Ratos , Ciclo-Oxigenase 2/metabolismo , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Inflamação/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Proteinúria , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , Humanos , Podócitos/metabolismo
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