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1.
Clin Exp Med ; 24(1): 236, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39361090

RESUMO

Proteinuria is a biomarker of kidney injury that typically results from glomerular and/or tubulointerstitial disease. Whereas kidney impairment with normal urinary protein excretion is usually less focused and understudied. We conducted a retrospective review of the renal histopathology of the patients with variable degrees of unexplained renal insufficiency but with normal range proteinuria between 2014 and 2024 of  three university teaching hospitals in Shenzhen city of Southern  China. Patients with kidney dysfunction of undetermined or uncertain etiology and with normal urinary protein excretion (defined by a 24hr urinary protein excretion < 150 mg or spot urinary protein to creatinine ratio [PCR] < 150 mg/g) were enrolled and analyzed. In a total of 2405 patients, 53 (2.2%) fulfilled the inclusion criteria  (male/female 40/13, age 47.3 ± 14.3 years) with a mean eGFR of 46.6 ± 16.8 ml/min per 1.73 m2. Glomerular disease (GD) was the most frequent pathological finding identified in 23 (43.4%) patients, while 19 (35.8%) cases  showed tubulointerstitial disease (TID) and 11 (20.8%) patients exhibited small vascular disease (SVD). Patients in the TID had the lowest mean eGFR and the highest numerical 24hr urinary protein excretion among the three groups. The incidence of acute kidney injury was significantly higher in TID than in other two groups. The patients in the SVD group had the highest fraction of underlying hypertension. Kidney dysfunction with normal range proteinuria may be related with, in descending order of probablity,  glomerular, tubulointerstitial and small vascular diseases. Renal biopsies were proved useful in informing therapeutic choice, long-term management and in predicting prognosis in this setting.


Assuntos
Rim , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , China/epidemiologia , Rim/patologia , Proteinúria , Taxa de Filtração Glomerular , Injúria Renal Aguda/patologia , Injúria Renal Aguda/etiologia , Idoso
2.
Gut Microbes ; 16(1): 2391521, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193618

RESUMO

N-Nitrosamine disinfection by-products (NAs-DBPs) have been well proven for its role in esophageal carcinogenesis. However, the role of intratumoral microorganisms in esophageal squamous cell carcinoma (ESCC) has not yet been well explored in the context of exposure to NAs-DBPs. Here, the multi-omics integration reveals F. periodonticum (Fp) as "facilitators" is highly enriched in cancer tissues and promotes the epithelial mesenchymal transition (EMT)-like subtype formation of ESCC. We demonstrate that Fp potently drives de novo synthesis of fatty acids, migration, invasion and EMT phenotype through its unique FadAL adhesin. However, N-nitrosomethylbenzylamine upregulates the transcription level of FadAL. Mechanistically, co-immunoprecipitation coupled to mass spectrometry shows that FadAL interacts with FLOT1. Furthermore, FLOT1 activates PI3K-AKT/FASN signaling pathway, leading to triglyceride and palmitic acid (PA) accumulation. Innovatively, the results from the acyl-biotin exchange demonstrate that FadAL-mediated PA accumulation enhances Wnt3A palmitoylation on a conserved cysteine residue, Cys-77, and promotes Wnt3A membrane localization and the translocation of ß-catenin into the nucleus, further activating Wnt3A/ß-catenin axis and inducing EMT phenotype. We therefore propose a "microbiota-cancer cell subpopulation" interaction model in the highly heterogeneous tumor microenvironment. This study unveils a mechanism by which Fp can drive ESCC and identifies FadAL as a potential diagnostic and therapeutic target for ESCC.


Assuntos
Transição Epitelial-Mesenquimal , Carcinoma de Células Escamosas do Esôfago , Nitrosaminas , Proteína Wnt3A , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Proteína Wnt3A/metabolismo , Proteína Wnt3A/genética , Nitrosaminas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/microbiologia , Carcinoma de Células Escamosas do Esôfago/genética , Linhagem Celular Tumoral , Lipoilação , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Animais , Camundongos , Movimento Celular/efeitos dos fármacos , Transdução de Sinais
3.
Cardiovasc Res ; 120(11): 1351-1364, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-38836630

RESUMO

AIMS: Abdominal aortic aneurysm (AAA) represents a life-threatening condition characterized by medial layer degeneration of the abdominal aorta. Nevertheless, knowledge regarding changes in regulators associated with aortic status remains incomplete. A thorough understanding of cell types and signalling pathways involved in the development and progression of AAAs is essential for the development of medical therapy. METHODS AND RESULTS: We harvested specimens of the abdominal aorta with different pathological features in Angiotensin II (AngII)-infused ApoE-/- mice, conducted scRNA-seq, and identified a unique population of interferon-inducible monocytes/macrophages (IFNICs), which were amply found in the AAAs. Gene set variation analysis revealed that activation of the cytosolic DNA sensing cGAS-STING and JAK-STAT pathways promoted the secretion of type I interferons in monocytes/macrophages and differentiated them into IFNICs. We generated myeloid cell-specific deletion of Sting1 (Lyz2-Cre+/-; Sting1flox/flox) mice and performed bone marrow transplantation and found that myeloid cell-specific deletion of Sting1 or Ifnar1 significantly reduced the incidence of AAA, aortic rupture rate, and diameter of the abdominal aorta. Mechanistically, the activated pyroptosis- and inflammation-related signalling pathways, regulated by IRF7 in IFNICs, play critical roles in the developing AAAs. CONCLUSION: IFNICs are a unique monocyte/macrophage subset implicated in the development of AAAs and aortic rupture.


Assuntos
Angiotensina II , Aorta Abdominal , Aneurisma da Aorta Abdominal , Ruptura Aórtica , Modelos Animais de Doenças , Progressão da Doença , Macrófagos , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Monócitos , Receptor de Interferon alfa e beta , Transdução de Sinais , Análise de Célula Única , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Macrófagos/efeitos dos fármacos , Monócitos/metabolismo , Monócitos/patologia , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismo , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Aorta Abdominal/imunologia , Ruptura Aórtica/prevenção & controle , Ruptura Aórtica/patologia , Ruptura Aórtica/metabolismo , Ruptura Aórtica/genética , Ruptura Aórtica/induzido quimicamente , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Masculino , RNA-Seq , Interferon Tipo I/metabolismo , Interferon Tipo I/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Janus Quinases/metabolismo , Células Cultivadas , Apolipoproteínas E
6.
Free Radic Biol Med ; 213: 512-522, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301975

RESUMO

Trace metal zinc is involved in key processes of solid tumors by its antioxidant properties, while the role of zinc at the onset of esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to determine whether zinc is associated with the ESCC and underlying molecular events involving malignant progression. Based on a case-control study, we found serum and urine zinc were decreased and correlated with ESCC progression. Thus, an in vitro model for zinc deficiency (ZD) was established, and we found that ZD contributed to the proliferation, migration, and invasion of EC109 cells. Untargeted metabolomics identified 59 upregulated metabolites and 6 downregulated metabolites, among which glycolysis and ferroptosis-related oxidation of chain fatty acids might play crucial steps in ZD-treated molecular events. Interestingly, ZD disrupted redox homeostasis and enhanced cytosolic Fe2+ of EC109 cells, while lipid peroxidation, the key marker of ferroptosis occurrence, was decreased after ZD treatment. The mechanism underlying these changes may involve ZD-enhanced ESCC glycolysis and lactate production, which confer ferroptosis resistance by inhibiting of p-AMPK and leading to the upregulation of SREBP1 and SCD1 to enhance the production of anti-ferroptosis monounsaturated fatty acids.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Ferroptose , Desnutrição , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Ácido Láctico , Estudos de Casos e Controles , Ferroptose/genética , Zinco/metabolismo , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
7.
Fitoterapia ; 173: 105834, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280683

RESUMO

The phytochemical investigation of the pericarps of Caesalpinia bonduc led to the isolation and identification of five new cassane-type alkaloids: caesalminines C - G (1-5) and six new diterpenoids: caesalbonducin K - P (6-11), along with seven known compounds (12-18). Compounds 1-5 were identified as a group of rare alkaloids possessing a tetracyclic cassane-type diterpenoid skeleton with a lactam D-ring instead of a typical furan or lactone moiety. The structures of 1-11 were elucidated on the basis of 1D and 2D NMR including HSQC, HMBC, COSY and NOESY, and other spectroscopic analyses. The cytotoxic activities of the isolated compounds were evaluated in the A431, A549 and U87MG cancer cell lines.


Assuntos
Alcaloides , Caesalpinia , Diterpenos , Caesalpinia/química , Estrutura Molecular , Alcaloides/análise , Espectroscopia de Ressonância Magnética , Diterpenos/química , Sementes/química
8.
Toxicol Sci ; 199(1): 12-28, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38291902

RESUMO

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed.


Assuntos
Desinfetantes , Água Potável , Neoplasias , Nitrosaminas , Humanos , Nitrosaminas/toxicidade , Desinfetantes/toxicidade , Neoplasias/induzido quimicamente , Neoplasias/metabolismo , Poluentes Químicos da Água/toxicidade , Animais , Desinfecção , Purificação da Água , COVID-19 , Carcinógenos/toxicidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-38087975

RESUMO

The prevalence of breast cancer as a major global cancer has underscored the importance of postoperative recovery for breast cancer patients. Among the issues, postoperative patients are prone to spinal deformities, including scoliosis, which has drawn significant attention from healthcare professionals. The primary aim of this study is to design a postoperative recovery platform for breast cancer patients that can effectively detect posture changes, provide feedback and support to medical staff, assist doctors in formulating recovery plans, and prevent spinal deformities. The feasibility of the recovery platform is also validated through experiments. The development and validation of the experimental recovery platform. The recovery platform includes instrument design, patient data collection, model training and fine-tuning, and postoperative body posture evaluation by comparing preoperative and postoperative conditions. The evaluation results are provided to doctors to facilitate the formulation of personalized postoperative recovery plans. This paper comprehensively designs and implements the recovery platform and verifies its feasibility through simulation experiments. Statistical methods were employed for the validation of the rehabilitation platform in simulated experiments, with a significance level of p < 0.05. In comparison to static assessments like CT scans, this paper introduces a dynamic detection method that provides a more insightful analysis of body posture. The experiments also demonstrate the preventive capability of this method against post-operative spinal deformities, ultimately enhancing patients' self-image, restoring their confidence, and enabling them to lead more fulfilling lives.

10.
Artigo em Inglês | MEDLINE | ID: mdl-37971439

RESUMO

Objective: To investigate the diagnostic value of transforming growth factor-ß1 (TGF-ß1), prostate-specific antigen isomer 2 (p2PSA) combined with a prostate-specific antigen (PSA) in prostate cancer (PCa). Methods: From October 1, 2019 to September 1, 2022 we enrolled a total of 90 patients with PCa90 patients with PCa in the urology department of our hospital were selected as the PCa group, 90 patients with benign prostatic hyperplasia (BPH) were selected as the BPH group, and 90 healthy people were selected as a healthy control group. The levels of TGF-ß1, p2PSA and PSA in serum were detected, and the differences in TGF-ß1, p2PSA and PSA levels among the three groups and PCa patients with different pathological parameters were compared. Univariate and Logistic regression analyses were used to analyze the independent risk factors affecting the occurrence of PCa. With pathological results as the 'gold standard', the diagnostic efficacy of TGF-ß1, p2PSA and PSA alone and their combination for PCa was analyzed by the receiver operating characteristic (ROC) curve. Results: The levels of serum PSA, p2PSA, and TGF-ß1 in the PCa group were higher than those in the BPH group and control group (P < .001), and those in BPH group were higher than those in the control group (P < .001). The serum indexes of PCa group increased with the increase of Glerson grade and TNM stage (P < .001). The serum indexes of patients with lymph and bone metastasis were significantly higher than those without lymph and bone metastasis (P < .001). Logistic regression analysis showed that PSA, p2PSA and TGF-ß1 were independent risk factors for PCa (P < .001). The area under the ROC curve (AUC) of PSA, p2PSA, TGF-ß1 and combined detection were 0.738, 0.862, 0.821 and 0.932, respectively. The AUC of combined detection was greater than that of single detection (P < .001). Conclusion: The expression levels of serum TGF-ß1, p2PSA and PSA are related to PCa and are independent risk factors for PCa. The combined detection of the three groups can improve the diagnostic efficacy of PCa. Combined testing improves diagnostic accuracy for prostate cancer, allows for early intervention, and improves patient survival and confidence in treatment options. This will significantly improve the clinical management of prostate cancer. Future studies could explore other biomarkers or molecular indicators to further improve the accuracy of diagnosis and grading of prostate cancer. Additionally, differences between different populations and subtypes can be studied to better understand the heterogeneity of prostate cancer.

11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1481-1485, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-37846704

RESUMO

OBJECTIVE: To investigate the correlation of iron metabolic parameters with platelet counts in blood donors. METHODS: A total of 400 blood donors who met requirements of apheresis platelet donation were collected, and their hematological parameters were analyzed. The donors were divided into low ferritin group and normal group, the differences of hematological parameters between the two groups were compared, and the correlation of iron metabolic parameters and routine hematology parameters with platelet counts were analyzed. RESULTS: Whether male or female, low ferritin group had higher platelet counts than normal group (P < 0.01). Among the iron metabolic parameters, the platelet counts was negatively correlated with serum ferritin (SF), serum iron (SI), and transferrin saturation (TSAT) (r =-0.162, r =-0.153, r =-0.256), and positively correlated with total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) (r =0.219, r =0.294) in female blood donors. Platelet counts was also negatively correlated with SF, SI and TSAT (r =-0.188, r =-0.148, r =-0.224) and positively correlated with UIBC (r =0.220) in male blood donors. Among the routine hematology parameters, platelet counts was negatively correlated with mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and reticulocyte hemoglobin equivalent (Ret-He) in female blood donors (r =-0.236, r =-0.267, r =-0.213, r =-0.284). Platelet counts was also negatively correlated with MCH, MCHC and Ret-He in male blood donors (r =-0.184, r =-0.221, r =-0.209). CONCLUSION: In blood donors with low C-reactive protein level, the lower the iron store capacity, the lower the iron utilization, and the platelet counts tends to rise.


Assuntos
Anemia Ferropriva , Ferro , Masculino , Humanos , Feminino , Ferro/metabolismo , Doadores de Sangue , Contagem de Plaquetas , Hemoglobinas , Ferritinas
12.
Nicotine Tob Res ; 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37788476

RESUMO

INTRODUCTION: The global disease burden may be exacerbated by exposure to passive smoking (SHS), with the workplace being a primary location for such exposure. Numerous epidemiological studies have identified SHS as a risk factor for diseases affecting various systems, including cardiovascular, respiratory, immune, endocrine, and nervous systems. The conventional observational study has certain methodological constraints which can be circumvented through a Mendelian randomization (MR) study. Our MR study intends to investigate the causal link between workplace exposure to SHS and the potential associated diseases. METHODS: Summary statistics data involving European participants was sourced from three databases: the UK Biobank, the FinnGen study, and the European Bioinformatics Institute. Genetic variants linked with exposure to SHS in the workplace were identified as instrumental variables. The MR was carried out using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity tests were also undertaken within the MR to evaluate the validity of the causality. RESULTS: According to the IVW model, genetically determined atrial fibrillation (AF) and stroke [P= 6.64E-04 and 5.68E-07, odds ratio = 2.030 and 2.494, 95% confidence interval = 1.350,3.051 and 1.743,3.569] were robustly associated with exposure to SHS in the workplace. Suggestive associations were found between workplace SHS and myocardial infarction (MI), asthma, and depression. CONCLUSIONS: The MR study demonstrates that exposure to SHS in the workplace is a significant risk factor for AF and stroke in European individuals. Whether workplace exposure to SHS influences other diseases and the causality between them requires further exploration. IMPLICATIONS: This study explored the causality between exposure to SHS in the workplace and potential associated diseases in multiple systems, including MI, AF, stroke, lung cancer, asthma, allergic disease, type 2 diabetes, and depression, using a MR study. The MR study can circumvent the methodological constraints of observational studies and establish a causal relationship. The two-sample MR analysis provides evidence supporting the causal association of frequent workplace SHS with AF and stroke. Individuals exposed to SHS in the workplace may also have a heightened risk of MI, asthma, and depression. However, whether SHS affects other diseases and the causality between them requires further investigation. To our knowledge, this is the first two-sample MR study to determine the causal relationship between SHS and potential diseases. As exposure to SHS in the workplace is a prevalent issue and may contribute to a global disease burden. The reduction of exposure following the introduction of smoke-free laws has led to a decrease in the admission rate for cardiac events and an improvement in health indicators. It is crucial to further advance smoke-free policies and their implementation.

13.
Front Immunol ; 14: 1260688, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744379

RESUMO

Introduction: Aortic aneurysms (AA) are prevalent worldwide with a notable absence of drug therapies. Thus, identifying potential drug targets is of utmost importance. AA often presents in the elderly, coupled with consistently raised serum inflammatory markers. Given that ageing and inflammation are pivotal processes linked to the evolution of AA, we have identified key genes involved in the inflammaging process of AA development through various bioinformatics methods, thereby providing potential molecular targets for further investigation. Methods: The transcriptome data of AA was procured from the datasets GSE140947, GSE7084, and GSE47472, sourced from the NCBI GEO database, whilst gene data of ageing and inflammation were obtained from the GeneCards Database. To identify key genes, differentially expressed analysis using the "Limma" package and WGCNA were implemented. Protein-protein intersection (PPI) analysis and machine learning (ML) algorithms were employed for the screening of potential biomarkers, followed by an assessment of the diagnostic value. Following the acquisition of the hub inflammaging and AA-related differentially expressed genes (IADEGs), the TFs-mRNAs-miRNAs regulatory network was established. The CIBERSORT algorithm was utilized to investigate immune cell infiltration in AA. The correlation of hub IADEGs with infiltrating immunocytes was also evaluated. Lastly, wet laboratory experiments were carried out to confirm the expression of hub IADEGs. Results: 342 and 715 AA-related DEGs (ADEGs) recognized from GSE140947 and GSE7084 datasets were procured by intersecting the results of "Limma" and WGCNA analyses. After 83 IADEGs were obtained, PPI analysis and ML algorithms pinpointed 7 and 5 hub IADEGs candidates respectively, and 6 of them demonstrated a high diagnostic value. Immune cell infiltration outcomes unveiled immune dysregulation in AA. In the wet laboratory experiments, 3 hub IADEGs, including BLNK, HLA-DRA, and HLA-DQB1, finally exhibited an expression trend in line with the bioinformatics analysis result. Discussion: Our research identified three genes - BLNK, HLA-DRA, and HLA-DQB1- that play a significant role in promoting the development of AA through inflammaging, providing novel insights into the future understanding and therapeutic intervention of AA.


Assuntos
Aneurisma Aórtico , Vacinas Anticâncer , Idoso , Humanos , Cadeias alfa de HLA-DR , Genes MHC da Classe II , Biologia Computacional , Inflamação/genética
14.
Mol Neurobiol ; 60(10): 6001-6017, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37400749

RESUMO

Realgar is a traditional Chinese medicine that contains arsenic. It has been reported that the abuse of medicine-containing realgar has potential central nervous system (CNS) toxicity, but the toxicity mechanism has not been elucidated. In this study, we established an in vivo realgar exposure model and selected the end product of realgar metabolism, DMA, to treat SH-SY5Y cells in vitro. Many assays, including behavioral, analytical chemistry, and molecular biology, were used to elucidate the roles of the autophagic flux and the p62-NRF2 feedback loop in realgar-induced neurotoxicity. The results showed that arsenic could accumulate in the brain, causing cognitive impairment and anxiety-like behavior. Realgar impairs the ultrastructure of neurons, promotes apoptosis, perturbs autophagic flux homeostasis, amplifies the p62-NRF2 feedback loop, and leads to p62 accumulation. Further analysis showed that realgar promotes the formation of the Beclin1-Vps34 complex by activating JNK/c-Jun to induce autophagy and recruit p62. Meanwhile, realgar inhibits the activities of CTSB and CTSD and changes the acidity of lysosomes, leading to the inhibition of p62 degradation and p62 accumulation. Moreover, the amplified p62-NRF2 feedback loop is involved in the accumulation of p62. Its accumulation promotes neuronal apoptosis by upregulating the expression levels of Bax and cleaved caspase-9, resulting in neurotoxicity. Taken together, these data suggest that realgar can perturb the crosstalk between the autophagic flux and the p62-NRF2 feedback loop to mediate p62 accumulation, promote apoptosis, and induce neurotoxicity. Realgar promotes p62 accumulation to produce neurotoxicity by perturbing the autophagic flux and p62-NRF2 feedback loop crosstalk.


Assuntos
Arsênio , Neuroblastoma , Humanos , Apoptose , Arsênio/toxicidade , Autofagia , Retroalimentação , Fator 2 Relacionado a NF-E2/metabolismo
15.
BMC Womens Health ; 23(1): 271, 2023 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-37198658

RESUMO

BACKGROUND: We aimed to compare the clinical efficacy of three surgical methods in the treatment of various types of cesarean scar pregnancy (CSP). METHODS: Herein, 314 cases of CSP were treated in the department of Obstetrics and Gynecology of the First Affiliated Hospital of Gannan Medical University between June 2017 and June 2020. The patients were divided into three groups based on the treatment received: group A (n = 146; curettage by pituitrin combined with ultrasonic monitoring and hysteroscopy-guided surgery), group B [n = 90; curettage after methotrexate (MTX) injection into the local gestational sac], and group C (n = 78; laparoscopic, transvaginal, and transabdominal cesarean scar resection). These groups were divided into three subgroups (type I, type II, and type III) according to the CSP type of the patients. RESULTS: The intraoperative blood loss, length of hospital stay, hospitalization cost, menstrual recovery time, and serum ß-HCG normalization time were lower in groups A than in groups B or C with type I, II and III CSP (P < 0.05). Operative efficiency and Successful second pregnancy rate were higher in groups A than in groups B or C with type I and II CSP (P < 0.05). But in type III CSP, the complications were more serious in group A than group C. CONCLUSIONS: Curettage by pituitrin combined with ultrasonic monitoring and hysteroscopy-guided surgery is an effective and relatively safe treatment for patients with type I and II CSP. Laparoscopic surgery is more suitable for type III CSP.


Assuntos
Gravidez Ectópica , Embolização da Artéria Uterina , Gravidez , Feminino , Humanos , Cicatriz/etiologia , Cicatriz/cirurgia , Cesárea/efeitos adversos , Estudos Retrospectivos , Gravidez Ectópica/cirurgia , Gravidez Ectópica/etiologia , Metotrexato/uso terapêutico , Resultado do Tratamento
16.
Nat Commun ; 14(1): 2654, 2023 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-37156795

RESUMO

Non-alcoholic steatohepatitis (NASH) has received great attention due to its high incidence. Here, we show that lysosomal-associated protein transmembrane 5 (LAPTM5) is associated with NASH progression through extensive bioinformatical analysis. The protein level of LAPTM5 bears a negative correlation with NAS score. Moreover, LAPTM5 degradation is mediated through its ubiquitination modification by the E3 ubquitin ligase NEDD4L. Discovered by experiments conducted on male mice, hepatocyte-specific depletion of Laptm5 exacerbates mouse NASH symptoms. In contrast, Laptm5 overexpression in hepatocytes exerts diametrically opposite effects. Mechanistically, LAPTM5 interacts with CDC42 and promotes its degradation through a lysosome-dependent manner under the stimulation of palmitic acid, thus inhibiting activation of the mitogen-activated protein kinase signaling pathway. Finally, adenovirus-mediated hepatic Laptm5 overexpression ameliorates aforementioned symptoms in NASH models.


Assuntos
Proteínas Imediatamente Precoces , Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Lisossomos/metabolismo , Transdução de Sinais , Fígado/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Imediatamente Precoces/metabolismo
17.
Materials (Basel) ; 16(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37109802

RESUMO

The paper presents the damage results of thick steel plates subjected to local blast loading using experimental and numerical approaches. Three steel plates with a thickness of 17 mm under the local contact explosion of trinitrotoluene (TNT) explosives were tested, and the damaged parts of the steel plates were scanned using a scanning electron microscope (SEM). ANSYS LS-DYNA software was used to simulate the damage results of the steel plate. By analyzing and comparing the experimental results with the numerical simulation results, the influence law of the TNT acting on the steel plate, the damage mode of the steel plate, the reliability verification of the numerical simulation, and the criterion for judging the damage mode of the steel plate were obtained. Results show that the damage mode of the steel plate changes with the changes in the explosive charge. The diameter of the crater on the surface of the steel plate is mainly related to the diameter of the contact surface between the explosive and the steel plate. The fracture mode of the steel plate in the process of generating cracks is a quasi-cleavage fracture, and the process of generating craters and perforations in the steel plate is a ductile fracture. The damage mode of the steel plates can be divided into three types. The numerical simulation results have minor errors and high reliability, and numerical simulation can be used as an auxiliary tool for experiments. A new criterion is proposed to predict the damage mode of the steel plates under contact explosion.

18.
Int J Anal Chem ; 2023: 1771563, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37057128

RESUMO

The harvest period of cultivated ginseng is generally 4-6 years. Ginseng flowers (GFs), the nonmedicinal parts, are usually removed every autumn, in which components are generally believed to stay unchanged with the increasing cultivation age. Recently, few documents were reported on the variation of volatile organic compounds (VOCs) and other components about ginseng flowers. This study had an insight into the variation of the chemical constituents with the cultivation ages through the comparison of the volatile organic compounds, gross ginsenosides, crude polysaccharide, and gross proteins of ginseng flowers from 3-, 4-, 5-, and 6-yr-old (GF3, GF4, GF5, and GF6) which were conducted by headspace solid-phase microextraction-gas chromatography-triple quadrupole mass spectrometry (HS-SPME-GC-QQQ/MS) and spectroscopic analysis combined with multivariate statistical analysis, including one-way ANOVA analysis and T test. The results indicated that the crude polysaccharide contents raised significantly depending on cultivation age except 6-yr-old, whereas the gross ginsenosides and the gross protein content were indistinctive. According to the peak intensity of determined VOCs, the contents of most differential compounds arranged in an order from high to low are GF3, GF4, GF5, and GF6, such as the compounds 2-15, 17-19, 22, and 25-26, therefore, they can be inferred that they are important markers to identify the age of GFs. 461 common differential compounds were gained and 26 common volatile organic compounds were identified with RSI >800 and RI and RIx no more than 30, including alcohols (such as 11, 12, and 15), sesquiterpenes (such as 2, 3, and 4), esters (such as 1 and 26), naphthalene and naphthol (such as 7 and 20), which had potential effects on curing Alzheimer's disease, inflammatory diseases, and prostate cancer based on network pharmacology analysis. This paper firstly revealed the variation rules of constitutions of GFs, which may provide a reference for the harvest and making rational application.

19.
Gynecol Endocrinol ; 39(1): 2190808, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36963422

RESUMO

OBJECTIVES: The study aimed to explore the role and mechanism of WZBS recipe on PCOS. METHODS: PCOS model was established. After modeling, PCOS rats were intragastrically administered with Diane-35 or WZBS recipe (6.93 g/kg/d). Then, the ovarian and uterine morphology were observed, the estrous cycle was assessed. HE and oil red O staining were conducted for ovarian morphological analysis and counting ovarian follicle and corpora lutea number. Furthermore, the serum content of testosterone (T) and sex-hormone-binding globulin (SHBG) were assessed by ELISA kits. The androgen receptor (AR), CX43 mRNA and protein expression were measured by q-PCR and Western blot. RESULTS: WZBS recipe increased uterine implanted blastocysts, reduced cystic dilated follicles, and normalized estrous cycle in PCOS rats. Meanwhile, WZBS recipe alleviated ovarian injury, increased mature follicles and corpora lutea number in PCOS rats. Moreover, WZBS recipe decreased serum T content, AR expression and increased serum SHBG content, CX43 expression in PCOS rats. CONCLUSIONS: This study reveals that WZBS recipe may attenuate PCOS by protecting follicular development via down-regulating AR.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Ratos , Animais , Receptores Androgênicos , Conexina 43/genética , Conexina 43/farmacologia , Folículo Ovariano/metabolismo
20.
Clin Lab ; 69(2)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36787553

RESUMO

BACKGROUND: Both plasma cell myeloma (PCM) and Waldenstrom's macroglobulinemia (WM) are mature B-cell neoplasms commonly involving bone marrow and usually related to paraproteinemia. METHODS: Secondary WM in a patient with PCM during maintenance therapy has not been previously reported. We herein report the first case of WM arising during maintenance therapy of PCM. RESULTS: The diagnosis of secondary WM during maintenance therapy of PCM was based on combination of medical history, morphology, flow cytometry, immunofixation electrophoresis, and molecular genetics. CONCLUSIONS: This case highlights the importance of an integrated diagnostic work-up, with an interesting role for morphology and flow immunotyping.


Assuntos
Linfoma de Células B , Mieloma Múltiplo , Macroglobulinemia de Waldenstrom , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Linfoma de Células B/complicações , Medula Óssea , Citometria de Fluxo
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