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1.
Psychiatry Investig ; 21(4): 321-328, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38695039

RESUMO

OBJECTIVE: To assess whether carbon monoxide (CO) poisoning increases the incidence of dementia. METHODS: We searched the Cochrane Library, PubMed, and EMBASE from inception to 14 August 2022. Two authors independently selected studies, assessed the quality of included studies, and extracted data. Any disagreement was resolved by discussion with a third author. Only cohort study with an enough follow-up period was included for systematic reviews and meta-analysis. RESULTS: Thirty-three full texts were initially searched, but only three studies met our inclusion criteria, and they were comprised of 134,563 participants who were initially free of dementia. The follow-up period ranged from 9 to 12 years. We found that CO poisoning increased the risk of dementia incidence (adjusted hazard ratio 2.61, 95% confidence interval 1.56 to 4.36, p=0.0003). Subgroup analysis showed that the increased dementia risk was significant in males but not in females, and the highest risk was in young age group, followed by in middle age group, but not in the old one. CONCLUSION: Overall the evidence from prospective cohort studies supported a link between CO exposure and an increased dementia risk, although all the included studies were limited to Taiwanese population.

2.
Front Oncol ; 14: 1373762, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601763

RESUMO

Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.

3.
Nat Prod Res ; : 1-7, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684029

RESUMO

Zanthoxylum nitidum is frequently used as a traditional Chinese medicine and food supplement. Our previous study revealed that its constituent compounds were able to inhibit cancer cell proliferation. In our continuous exploration of bioactive compounds in Z. nitidum, we isolated ten alkaloids (1-10), including one new natural compound (1), and nine known alkaloids (2-10), from an ethanolic extract of the whole plant. The chemical structures were elucidated based on a combination of comprehensive NMR and HRESIMS analyses. Compounds 5, 8 and 10 exhibited significant antiproliferative effects against A549 cancer cell lines. We further elucidated the underlying molecular mechanisms of the antiproliferative activity of compound 8 in A549 human lung cancer cells. Compound 8 was found to induce cell cycle arrest in the G0/G1 phase via p53 activation and CDK4/6 suppression. Compound 8 also effectively inhibited cell migration through the modulation of the epithelial-mesenchymal transition (EMT), as indicated by the expression of biomarkers, such as N-cadherin downregulation and E-cadherin upregulation. Compound 8 significantly suppressed the activation of the EGFR/AKT/mTOR signalling pathway in A549 cells. These results indicate that alkaloid 8 from Z. nitidum has potential to be a lead antiproliferative compound in cancer cells.

4.
Heliyon ; 10(7): e28780, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38586402

RESUMO

Objective: Diabetes mellitus and chronic kidney disease are multifactorial conditions with multiple etiologies that share similar pathophysiologies. This nationwide cohort study examined the impact of diabetes mellitus on the follow-up development of chronic kidney disease. Methods: By retrieving the Longitudinal Health Insurance Database 2005, 5121 patients with diabetes mellitus were included in this study and 5121 patients without diabetes mellitus, who were matched according to sex, age, and Charlson comorbidity index made up the control group. The adjusted hazard ratios for chronic kidney disease were calculated using Cox proportional hazards regression analysis. Kaplan-Meier analysis was used to estimate the cumulative incidence of chronic kidney disease rate in the diabetes mellitus and control groups. Results: After adjusting for sex, age, and Charlson comorbidity index score, the diabetes mellitus group had a 1.380 times higher (95% CI: 1.277-1.492) risk of developing chronic kidney disease than the control group. Further stratified analysis showed that patients with diabetes mellitus had a significantly higher risk of developing chronic kidney disease regardless of their sex, age, and Charlson comorbidity index score, compared to those without diabetes mellitus. Conclusions: There is a possibility that diabetes mellitus serves as an independent risk factor for chronic kidney disease development. Early screening and monitoring of diabetes mellitus appear to be of great importance in the prevention of chronic kidney disease.

5.
Placenta ; 147: 42-51, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38308901

RESUMO

INTRODUCTION: Preterm birth (PTB) frequently results from the syndrome of preterm labor (PTL). PTL is linked to an atypical maternal inflammatory response, as well as intrauterine inflammation and/or infection. In this study, we explored the mechanisms involved in nicotine-mediated abnormal macrophage polarization and trophoblast invasion associated with PTL. METHODS: First, THP-1-M0 macrophages were generated by treating the human monocytic leukemia cell line (THP-1) with phorbol 12-myristate 13-acetate for a duration of 24 h. Afterward, nicotine treatment was administered, followed by coculturing with the HTR-8/SVneo trophoblast cell line (HTR-8) at a ratio of 1:1. Next, we transfected sh-α7nAChR and treated THP-1-M0 macrophages and HTR-8 cells with nicotine. In addition, we transfected THP-1-M0 macrophages with sh-NC or sh-SIRT1 or subjected them to 4 nM nicotinamide adenine dinucleotide (NAD) metabolic inhibitor FK866 treatment. Moreover, HTR-8 cells were treated with nicotine, after which THP-1-M0 macrophages were cocultured with HTR-8 cells. Finally, we constructed an in vivo RU486-induced PTL rat model to verify the effect of nicotine and the mechanisms involved. RESULTS: We found that nicotine affected polarization and α7nAChR expression in HTR-8 cocultured THP-1-M0 macrophages. Knocking down α7nAChR blocked the effect of nicotine on the proliferation and invasion of HTR-8 cells. Furthermore, nicotine activated the α7nAChR/SIRT1 axis to regulate THP-1-M0 macrophage polarization through the cholinergic anti-inflammatory pathway. Additionally, NAD metabolism mediated the role of the α7nAChR/SIRT1 axis in nicotine-induced polarization of HTR-8 cocultured THP-1-M0 macrophages. In vivo experiments demonstrated that nicotine alleviated inflammation in PTL rats, which involved the α7nAChR/SIRT1 axis. CONCLUSION: Nicotine regulated abnormal macrophage polarization and trophoblast invasion associated with PTL via the α7nAChR/SIRT1 axis.


Assuntos
Nicotina , Nascimento Prematuro , Recém-Nascido , Feminino , Humanos , Ratos , Animais , Nicotina/farmacologia , Nicotina/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Sirtuína 1/metabolismo , NAD/metabolismo , NAD/farmacologia , Movimento Celular , Nascimento Prematuro/metabolismo , Trofoblastos/metabolismo , Macrófagos/metabolismo , Inflamação/metabolismo
6.
Surgery ; 175(5): 1368-1376, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38395638

RESUMO

BACKGROUND: To assess the correlation between clinical outcomes and diagnostic accuracy of evaluations carried out by a preoperative multidisciplinary team versus standard surgical care for patients with retroperitoneal liposarcoma undergoing surgery. METHODS: This comparative study was conducted retrospectively at a specialist assessment center within Zhongshan Hospital, Fudan University, China, between April 2011 and March 2021. Patients were assigned to a multidisciplinary team or nonmultidisciplinary team cohort based on referral to the multidisciplinary team. The primary outcome measured was long-term clinical prognosis, with other outcomes including diagnostic accuracy, 30-day reoperation, duration of stay, perioperative mortality, and medical complications. To mitigate selection bias, we conducted propensity-score matching. Uni- and multivariable Cox proportional hazard models were then used to evaluate the effect of multidisciplinary teams on postoperative survival. The previously specified questionnaire was used to measure the enhancement of awareness and treatment adherence facilitated by multidisciplinary team management. Data analysis was carried out between January 2023 and August 2023. RESULTS: Of the 521 records that were screened, 139 patients were deemed eligible for inclusion and defined as the multidisciplinary team cohort. At the same time, 382 patients without multidisciplinary team management were also included during that period and defined as the nonmultidisciplinary team cohort. The multidisciplinary team cohort exhibited lower numbers of primary retroperitoneal liposarcoma but a higher tumor grade and a greater proportion of R2 resection. After propensity-score matching, the 1-, 3-, and 5-year overall survival rates were 89.5%, 70.5%, and 62.9%, respectively, in the multidisciplinary team cohort, and 77.1%, 49.8%, and 45.1% in the nonmultidisciplinary team cohort. The diagnostic consistency of the multidisciplinary team group was significantly superior to that of the nonmultidisciplinary cohort (92.5% vs 83.6%, P = .042). Although no significant links were shown with duration of stay (P = .232) and 30-day reoperation (P = .447), the multidisciplinary team participation was linked to a substantial decrease in perioperative mortality (P = .036) and postoperative complications (P = .002). Additionally, the multidisciplinary team group indicated stronger illness awareness and postoperative adherence among individuals with retroperitoneal liposarcoma. CONCLUSION: The study's findings indicate that multidisciplinary team management could result in improved clinical outcomes, higher diagnostic accuracy, and reduced duration of postoperative stays, complications, and perioperative mortality. The intervention may also enhance disease awareness and postoperative compliance in retroperitoneal liposarcoma patients who undergo surgery. However, evidence quality was deemed low, and prospective studies with robust designs are required. Nonetheless, these results are worth considering.


Assuntos
Lipossarcoma , Neoplasias Retroperitoneais , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Lipossarcoma/diagnóstico , Lipossarcoma/cirurgia , Neoplasias Retroperitoneais/cirurgia
7.
BMC Public Health ; 24(1): 334, 2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297296

RESUMO

BACKGROUND: Prisoner health is a topic of significant importance; however, it has received limited attention in epidemiological studies, likely because of challenges in obtaining relevant data. Specifically, research on ocular disorders among elderly prisoners is lacking. Thus, the aim of this study was to evaluate the prevalence of disorders of the eye and adnexa among elderly prisoners in Taiwan. METHODS: We investigated the presence of eye and adnexal disorders in elderly prisoners in Taiwan using data from the Taiwan National Health Insurance Research Database. The ocular disorders were identified using the appropriate disease codes in the International Classification of Diseases, 9th revision Clinical Modification (codes 360-379). In addition, the most common types of eye and adnexal disorders among the prisoners were identified. RESULTS: A total of 2215 elderly prisoners (age ≥ 65 years; 2073 men and 142 women) were examined. The prevalence of eye and adnexal disorders among the prisoners was 18.87%. The elderly female prisoners exhibited a higher prevalence of eye and adnexal disorders than the elderly male prisoners. The most common disorders were disorders of the conjunctiva, cataract, and disorders of the lacrimal system. CONCLUSIONS: A considerable proportion of elderly prisoners have disorders of the eye and adnexa. The overall quality of life of elderly prisoners can be improved by addressing their visual health, which contributes to the fulfillment of their basic human rights.


Assuntos
Prisioneiros , Prisões , Humanos , Masculino , Feminino , Idoso , Prevalência , Taiwan/epidemiologia , Qualidade de Vida
8.
Curr Med Chem ; 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37936458

RESUMO

BACKGROUND: Acute myocardial infarction (AMI) is an age-dependent cardiovascular disease in which cell aging, immunity, and inflammatory factors alter the course; however, cell aging-immune/inflammation signatures in AMI have not been investigated. METHODS: Based on the GEO database to obtain microRNA (miRNA) sequencing, mRNA sequencing and single-cell sequencing data, and utilizing the Seurat package to identify AMI-associated cellular subpopulations. Subsequently, differentially expressed miRNAs and mRNAs were screened to establish a network of competing endogenous RNAs (ceRNAs). Senescence and immunity scores were calculated by single sample gene set enrichment analysis (ssGSEA), ESTIMATE and CIBERSORT algorithms, and the Hmisc package was used to screen for genes with the highest correlation with senescence and immunity scores. Finally, protein-protein interaction (PPI) and molecular docking analyses were performed to predict potential therapeutic agents for the treatment of AMI. RESULTS: Four cell types (Macrophage, Fibroblast, Endothelial cells, CD8 T cells) were identified in AMI, and CD8 T cells exhibited the lowest cell aging activity. A ceRNA network of miRNAs-mNRA interactions was established based on the overlapping genes in differentially expressed miRNAs (DEmiRNAs) target genes and differentially expressed mRNAs (DEmRNAs). Twenty-four marker genes of CD8 T cells were observed. LIMD2 was identified as cell aging-immune/inflammation-related hub gene in AMI. This study also identified a potential therapeutic network of DB03276-LIMD2-AMI, which showed excellent and stable binding status between DB03276-LIMD2. CONCLUSION: This study identified LIMD2 as a cell aging-immune/inflammation-related hub gene. The understanding of the pathogenesis and therapeutic mechanisms of AMI was enriched by the ceRNA network and DB03276-LIMD2-LAMI therapeutic network.

9.
Front Med (Lausanne) ; 10: 1239902, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37937139

RESUMO

Background: The reasons for the recurrence of common bile duct stones (CBDS) in elderly patients after choledocholithotomy are still unclear. This study aims to establish a prediction model for CBDS recurrence by identifying risk factors. Methods: We conducted a retrospective analysis of 1804 elderly patients aged 65 years and above who were diagnosed to have CBDS and were admitted to Nanjing First Hospital between January 1, 2010, and January 1, 2021. According to inclusion and exclusion criteria, 706 patients were selected for the final analysis. The patients were assigned to two groups according to the presence or absence of CBDS recurrence, and their clinical data were then statistically analyzed. Subsequently, a prediction model and nomogram were developed, evaluating effectiveness using the concordance index (C-index). Results: Of the 706 elderly patients, 62 patients experienced CBDS recurrence after surgery, resulting in a recurrence rate of 8.8%. The multivariate Cox analysis showed that prior history of cholecystectomy (hazard ratio [HR] = 1.931, 95% confidence interval [CI]: 1.051-3.547, p = 0.034), white blood cell (WBC) count ≥11.0 × 109/L (HR = 2.923, 95% CI: 1.723-4.957, p < 0.001), preoperative total bilirubin (TBIL) level ≥ 36.5 mmol/L (HR = 2.172, 95% CI: 1.296-3.639, p = 0.003), number of stones ≥2 (HR = 2.093, 95% CI: 1.592-5.294, p = 0.001), maximum stone diameter ≥ 0.85 cm (HR = 1.940, 95% CI: 1.090-3.452, p = 0.024), and T-tube drainage (HR = 2.718, 95% CI: 1.230-6.010, p = 0.013) were independent risk factors of CBDS recurrence in elderly patients after choledocholithotomy. A postoperative CBDS recurrence prediction model was constructed with a C-index value of 0.758 (95% CI: 0.698-0.818) and internal validation value of 0.758 (95% CI: 0.641-0.875). Conclusion: A history of cholecystectomy, WBC count ≥11.0 × 109/L, preoperative TBIL level ≥ 36.5 mmol/L, number of stones ≥2, maximum stone diameter ≥ 0.85 cm, and T-tube drainage are the independent risk factors of CBDS recurrence after choledocholithotomy in elderly patients. Our developed prediction model for CBDS recurrence has good predictive ability and can help predict the prognosis of patients with CBDS.

10.
BMC Pregnancy Childbirth ; 23(1): 633, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660016

RESUMO

PURPOSE: The impact of body mass index (BMI) on in vitro fertilization (IVF) has been well acknowledged; however, the reported conclusions are still incongruent. This study aimed to investigate the effect of BMI on IVF embryos and fresh transfer clinical outcomes. METHODS: This retrospective cohort analysis included patients who underwent IVF/ICSI treatment and fresh embryo transfer from 2014 to March 2022. Patients were divided into the underweight group: BMI < 18.5 kg/m2; normal group: 18.5 ≤ BMI < 24 kg/m2; overweight group: 24 ≤ BMI < 28 kg/m2; and obesity group: BMI ≥ 28 kg/m2. A generalized linear model was used to analyze the impact of BMI on each IVF outcome used as a continuous variable. RESULTS: A total of 3465 IVF/ICSI cycles in the embryo part; and 1698 fresh embryo transplanted cycles from the clinical part were included. Available embryos rate (61.59% vs. 57.32%, p = 0.007) and blastocyst development rates (77.98% vs. 66.27%, p < 0.001) were higher in the obesity group compared to the normal BMI group. Also, the fertilization rate of IVF cycles in the obesity group was significantly decreased vs. normal BMI group (normal: 62.95% vs. 66.63% p = 0.006; abnormal: 5.43% vs. 7.04%, p = 0.037), while there was no difference in ICSI cycles. The clinical outcomes of overweight and obesity groups were comparable to the normal group. The gestational age of the obesity group was lower compared to the normal group (38.08 ± 1.95 vs. 38.95 ± 1.55, p = 0.011). The adjusted OR (AOR) of BMI for the preterm birth rate of singletons was 1.134 [(95% CI 1.037-1.240), p = 0.006]. BMI was significantly associated with live birth rate after excluded the PCOS patients [AOR: 1.042 (95% CI 1.007-1.078), p = 0.018]. In young age (≤ 35 years), clinical pregnancy rate and live birth rate were positively correlated with BMI, AOR was 1.038 [95% CI (1.001-1.076), p = 0.045] and 1.037 [95% CI (1.002-1.074) p = 0.038] respectively. CONCLUSION: Being overweight and obese was not associated with poor IVF outcomes but could affect blastocyst formation. ICSI could help to avoid low fertilization in obese patients. Also, obesity was associated with increased rates of premature singleton births.


Assuntos
Sobrepeso , Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , Adulto , Sobrepeso/complicações , Sobrepeso/epidemiologia , Estudos Retrospectivos , Obesidade/complicações , Obesidade/epidemiologia , Fertilização in vitro
11.
Front Immunol ; 14: 1209396, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37483592

RESUMO

Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model. Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis. Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings. Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.


Assuntos
Neoplasias Retroperitoneais , Humanos , Neoplasias Retroperitoneais/genética , Ecossistema , Metabolismo dos Lipídeos , Prognóstico , Ácidos Graxos
12.
Gastroenterology ; 165(3): 746-761.e16, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37263311

RESUMO

BACKGROUND & AIMS: Liver fibrosis is an intrinsic wound-healing response to chronic injury and the major cause of liver-related morbidity and mortality worldwide. However, no effective diagnostic or therapeutic strategies are available, owing to its poorly characterized molecular etiology. We aimed to elucidate the mechanisms underlying liver fibrogenesis. METHODS: We performed a quantitative proteomic analysis of clinical fibrotic liver samples to identify dysregulated proteins. Further analyses were performed on the sera of 164 patients with liver fibrosis. Two fibrosis mouse models and several biochemical experiments were used to elucidate liver fibrogenesis. RESULTS: We identified cathepsin S (CTSS) up-regulation as a central node for extracellular matrix remodeling in the human fibrotic liver by proteomic screening. Increased serum CTSS levels efficiently predicted liver fibrosis, even at an early stage. Secreted CTSS cleaved collagen 18A1 at its C-terminus, releasing endostatin peptide, which directly bound to and activated hepatic stellate cells via integrin α5ß1 signaling, whereas genetic ablation of Ctss remarkably suppressed liver fibrogenesis via endostatin reduction in vivo. Further studies identified macrophages as the main source of hepatic CTSS, and splenectomy effectively attenuated macrophage infiltration and CTSS expression in the fibrotic liver. Pharmacologic inhibition of CTSS ameliorated liver fibrosis progression in the mouse models. CONCLUSIONS: CTSS functions as a novel profibrotic factor by remodeling extracellular matrix proteins and may represent a promising target for the diagnosis and treatment of liver fibrosis.


Assuntos
Endostatinas , Proteômica , Camundongos , Animais , Humanos , Endostatinas/metabolismo , Endostatinas/farmacologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Fibrose , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Matriz Extracelular , Macrófagos/metabolismo
13.
Biochim Biophys Acta Gene Regul Mech ; 1866(2): 194928, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36948453

RESUMO

Liver fibrosis is characterized by excessive synthesis and deposition of extracellular matrix (ECM) in liver tissues. However, it still has been lacking of early detection and diagnosis methods. The collagen hybridizing peptide (CHP) is a novel synthetic peptide that enables detection of collagen damage and tissue remodeling. Here, we showed that obvious CHP-positive staining could be detected in the liver while given CCl4 for only 3 days, which was significantly enhanced while given CCl4 for 7 days. However, H&E staining showed no significant changes in fibrous tissue, and sirius red-positive staining could only be observed while given CCl4 for 14 days. Moreover, CHP-positive staining enhanced initially at portal area which further extended into the hepatic lobule, which was increased more significantly than sirius red-positive staining in the model of 10 and 14 days. Further proteomic analysis of CHP-positive staining revealed that pathways associated with ECM remodeling were significantly increased, while retinol metabolism was downregulated. Meanwhile, proteins enriched in cellular gene transcription and signal transduction involved in fibrogenesis were also upregulated, suggesting that fibrosis occurred in CHP-positive staining. Our study provided evidence that CHP could detect the collagen damage in liver, which might be an efficient indicator for the diagnosis of liver fibrosis at a very early stage.


Assuntos
Cirrose Hepática , Proteômica , Humanos , Cirrose Hepática/diagnóstico , Cirrose Hepática/metabolismo , Colágeno/química , Peptídeos/química
14.
Adv Mater ; 35(15): e2211237, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36662770

RESUMO

Hydrogels with wet adhesion are promising interfacial adhesive materials; however, their adhesion in water, oil, or organic solvents remains a major challenge. To address this, a pressure-sensitive P(AAm-co-C18 )/PTA-Fe hydrogel is fabricated, which exhibits robust adhesion to various substrates in both aqueous solutions and oil environments. It is demonstrated that the key to wet adhesion under liquid conditions is the removal of the interfacial liquid, which can be achieved through rational molecular composition regulation. By complexing with hydrophilic polymer networks, phosphotungstic acid (PTA) is introduced into the hydrogel network as a physical cross-linker and anchor point to improve the cohesion strength and drive the migration of polymer chains. The migration and rearrangement of hydrophilic and hydrophobic polymer chains on the hydrogel surface are induced by the electrostatic interactions of Fe3+ , which create a surface with interfacial water- and oil-removing properties. By co-regulating the hydrophilic and hydrophobic polymer chains, the P(AAm-co-C18 )/PTA-Fe hydrogel is able to act as a pressure-sensitive adhesive under water and oils with adhesion strength of 92.6 and 90.0 kPa, respectively. It is anticipated that this regulation strategy for polymer chains will promote the development of wet adhesion hydrogels, which can have a wide range of applications.

15.
Behav Brain Res ; 438: 114219, 2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36403671

RESUMO

Using functional near-infrared spectroscopy (fNIRS), hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) were measured while participants with Parkinson's disease (PD) and healthy controls performed the Timed-Up-and-Go test (TUGT), and differences in cortical activity at baseline and three different intervals were examined between the two groups. Seventeen PD patients and twenty-two controls participated in the study, but two PD patients were excluded from statistical analysis due to the presence of freezing of gait and using walking aids during the TUGT. During the TUGT, activity in the front, left, right and total frontal cortices initially decreased significantly, then significantly increased in PD participants and low-risk faller PD participants, compared to when in a sitting position. ΔHbO (HbO change from baseline) over the front, left and total frontal cortices in the PD group was significantly lower than the control group in interval 1 (P = 0.019, P = 0.014 and P = 0.031, respectively), while significantly higher than the control group in interval 2 over the left frontal cortex (P = 0.010). No significant differences were observed between the high-risk faller and low-risk faller subgroups of PD participants in ΔHbO and ΔHbR in the three intervals (P > 0.05). In the high-risk faller subgroup, ΔHbO over the left frontal cortex was significantly higher than the right frontal cortex in interval 2 and interval 3 (P = 0.015, P = 0.030, respectively). There was a strong positive correlation between education and HbR concentration over the right frontal cortex in PD participants (rho = 0.557, P = 0.031), while there were strong negative correlations between PD duration and HbR concentration over the right and total frontal cortices in the high-risk faller subgroup of PD participants (rho = -0.854, P = 0.014 for the right; rho = -0.784, P = 0.037 for the total). The falls prediction cutoff TUGT time for PD participants was 14.2 s. These results suggest that frontal cognition training, along with exercise training, could be used as an effective training method to improve motor performance in PD patients, especially for those at high-risk for falls.


Assuntos
Transtornos Neurológicos da Marcha , Doença de Parkinson , Humanos , Equilíbrio Postural , Espectroscopia de Luz Próxima ao Infravermelho , Estudos de Tempo e Movimento , Hemodinâmica
16.
Stem Cell Rev Rep ; 19(1): 230-247, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35962935

RESUMO

Resent study suggests that c-kit+ cells in bone marrow-derived MSCs may differentiate toward cardiamyocytes. However, the properties of c-kit+ MSCs remain unclear. This study isolated c-kit+VEGFR-2+ cells from rat bone marrow-derived MSCs, and assessed potential of c-kit+VEGFR-2+ MSCs to differentiate towards cardiovascular cells and their efficiency of repairing the infarcted myocardium after transplantation. Gene expression profile of the cells was analyzed with RNA-sequencing. Potential of differentiation of the cells was determined after induction. Rat models of myocardial infarction were established by ligation of the left anterior descending coronary artery. The cells were treated with hypoxia and serum deprivation for four hours before transplantation. Improvement of cardiac function and repair of the infarcted myocardium were assessed at four weeks after transplantation. Gene expression profile revealed that c-kit+VEGFR-2+ MSCs expressed most smooth muscle-specific and myocardium-specific genes, while expression of endothelium-specific genes was upregulated significantly. After induction with VEGF or TGF-ß for two weeks, the cells expressed CD31 and α-SMA respectively. At three weeks, BMP-2-induced cells expressed cTnT. After transplantation of the cells, cardiac function was improved, scar size of the infarcted myocardium was decreased, and angiogenesis and myocardial regeneration were enhanced significantly. Moreover, paracrine in the myocardium was increased after transplantation. These results suggest that c-kit+VEGFR-2+ MSCs have a potential of differentiation towards cardiovascular cells. Transplantation of c-kit+VEGFR-2+ MSCs is effective for repair of the infarcted myocardium. c-kit+VEGFR-2+ MSCs may be a reliable source for cell therapy of ischaemic diseases.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Infarto do Miocárdio , Ratos , Animais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo
17.
Ann Transl Med ; 10(4): 218, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35280359

RESUMO

Background: Colonic mucosal injuries are an important manifestation of ulcerative colitis (UC), which is related to hypoxia-induced glycolysis in colonic mucosal epithelial cells (cmECs). Panax notoginseng (PN) promotes the repair of colonic mucosal injuries by inhibiting hypoxia-induced glycolysis in cmECs; However, the mechanism by which this occurs is not completely clear. Here, we are to investigate the effects of PN on glucose metabolism in cmECs in colitis and the underlying mechanism. Methods: A model of dextran sulfate sodium-induced colitis rats was used in this research, and the severity of colitis was assessed by pathology, disease activity index (DAI), and weight changes. The content of intracellular pyruvate, intracellular lactate, adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial ROS (mtROS), myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity, and inflammatory cytokines was detected by assay kits. The expression levels of proteins were detected by western blotting. The expression levels of the ATP4a gene were detected by quantitative polymerase chain reaction (QT-PCR). Results: The colonic mucosal injuries of the colitis rats were significantly worse than those of the control group. Specifically, the hypoxia-induced glycolysis and potential of hydrogen (pH) in the colonic lumen were increased, and the expression of ATP4a was downregulated in the colitis rats. PN (1.0 g/kg) promoted the repair of colonic mucosal injuries, and reversed the pH in the colonic lumen. Further, PN increased the expression of ATP4a proteins, the content of ATP, and the SOD activity, and decreased the expression of pyruvate dehydrogenase lipoamide kinase isozyme and hypoxia-inducible factor 1-alpha proteins, the content of ROS, and MPO activity in cmECs in colitis. PN also increased the expression of ATP4a, cytochrome P450 family 21 subfamily a member 2, and hydroxy-delta-5-steroid dehydrogenase, 3 beta and steroid delta-isomerase 2 proteins in the mitochondria, and decreased the content of mtROS in cmECs. Conclusions: PN alleviated the pH in the colonic lumen and hypoxia-induced glycolysis in cmECs by reducing the hypoxia-induced glycolysis caused by the downregulation of ATP4a protein, thereby promoting the repair of colonic mucosal injuries in colitis.

18.
Chemosphere ; 298: 134187, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35271905

RESUMO

Developing an efficient approach to decompose ground-level O3 in humidity is crucial for preventing O3 pollution in practical application scenes. In this study, MnOx, CuO, and Cu/MnOx were synthesized to investigate the influence of H2O on the variation of active sites during O3 decomposition. The structural characterizations of the as-synthetic catalysts were measured by N2 physisorption, XRD, SEM, O2-TPD, H2-TPR, TG, and FT-IR analyses. In dry conditions, the elimination rate of O3 followed the sequence of MnOx > Cu/MnOx > CuO. The introduction of Cu to MnOx enhanced the surface area and pore volume of Cu/MnOx, accordingly diminishing the amounts of surface defects and the participation of sub-surface lattice oxygen for catalytic cycle, indicating that surface defects and oxygen vacancies (VO) determined the catalytic activity for O3 decomposition. In humid conditions, the elimination rate of O3 changed to the sequence of Cu/MnOx > MnOx > CuO, with a variation rate compared to dry conditions of -62.9% for MnOx, 14.2% for CuO, and 27.7% for Cu/MnOx. The decrease of participant sub-surface lattice oxygen and the accumulation of intermediates in humidity diminished the decomposition of O3 on MnOx, while the active species such as superoxide radicals generating from the reaction of H2O and Cu/MnOx facilitated the participation of VO and the desorption of O2 from the occupied active sites, accelerating the catalytic cycle on Cu/MnOx. This work developed a deeper understanding of the influence of H2O on catalytic activity, promoting the performance of MnOx-based catalysts for practical O3 decomposition.


Assuntos
Ozônio , Catálise , Domínio Catalítico , Humanos , Compostos de Manganês , Óxidos , Oxigênio , Ozônio/química , Espectroscopia de Infravermelho com Transformada de Fourier , Água
19.
Arch Gynecol Obstet ; 305(3): 757-765, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34510243

RESUMO

PURPOSE: Sequential media G5 series (Vitrolife) and single-step medium Continuous Single Culture Complete (CSC-C) (Irvine Scientific) are two different culture media. We want to examine difference between culturing effects of the two media. METHODS: To compare the fertilization and early embryo development, a prospective randomized controlled trial with sibling oocytes in infertile patients, aged ≤ 45 years with ≥ 8 oocytes (226 cycles) was conducted. Each half of the retrieved oocytes from the same patient were randomly allocated to two culture media separately. The remaining fresh cycles were randomly assigned to two culture media during the same period (179 cycles). We compared the clinical outcomes based on the total fresh ET cycles in this periods, in which the transferred embryos were only from one culture medium. RESULTS: Embryo outcomes: 226 cycles, included 176 IVF and 50 ICSI cycles, were analyzed, which correspond to 3518 inseminated or micro-injected oocytes. CLINICAL OUTCOMES: 71 (CSC-C) and 71 (G5 series) fresh ET cycles were compared. There were no significant differences in clinical outcomes and general fertilization rate. However, the fertilization rate was superior in the CSC-C when compared with G5 in ICSI cycles (76.51% vs. 67.25%, P = 0.008). In addition, the compacted embryo development rate was significantly higher in CSC-C on day 3. The cycles that had compacted embryos on day 3 demonstrated better outcomes both in embryos as well as clinically. CONCLUSIONS: CSC-C had higher fertilization rates than G5 series in ICSI cycles. In addition, the compaction rates of day 3 embryos were significantly higher in CSC-C.


Assuntos
Técnicas de Cultura Embrionária , Fertilização in vitro , Meios de Cultura , Feminino , Humanos , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas
20.
Front Public Health ; 9: 739119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900895

RESUMO

Purpose: To analyze the key factors and decision-making behaviors affecting overall satisfaction based on perceptual data of outpatients. Methods: The official satisfaction questionnaire developed by the National Health Commission of the People's Republic of China was used. Rough set theory was used to identify the perception patterns between condition attributes (i.e., service factors) and a decision attribute (i.e., overall service level) and to express them in rule form (i.e., if-then). Results: The four minimal-coverage rules, with strength exceeding 10% in the good class, and six crucial condition attributes were obtained: "Ease of registration (C1)," "Respected by registered staff (C2)," "Registered staff's listening (C3)," "Respected by doctor (C9)," "Signpost (C12)," and "Privacy (C16)." In addition, the average hit rate for 5-fold cross-validation was 90.86%. Conclusions: A series of decision rules could help decision-makers easily understand outpatients' situations and propose more suitable programs for improving hospital service quality because these decision rules are based on actual outpatient experiences.


Assuntos
Assistência Ambulatorial , Hospitais Públicos , Humanos , Pacientes Ambulatoriais , Inquéritos e Questionários
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