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1.
Front Public Health ; 10: 893673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35685761

RESUMO

Background: Promoting cervical cancer screening (CCS) is undoubtedly effective in combating severe public health problems in developing countries, but there are challenges to its implementation. Understanding the factors influencing primary care physicians' intentions to provide CCSs to rural women is crucial for the future implementation of screening programs. The aim of this study was to assess the intentions of primary care physicians to provide cervical cancer screening services (CCSSs) to rural women and their determinants. Methods: This cross-sectional study included 1,308 primary care physicians in rural primary health care, and the data collection tool was developed based on the theory of planned behavior (TPB), which included demographic characteristics, the basic constructs of TPB, and the degree of knowledge of CCSSs as an extended variable of the TPB model. Structural equation modeling was used to analyze the relationships between each factor. Results: Pathway analysis found that TPB is an appropriate theoretical basis for predicting primary care physicians' intent to provide CCSSs (χ2/df = 2.234 < 3, RMSEA = 0.035, and SRMR = 0.034). Meanwhile, the structural equation model showed that attitude (ß = 0.251, p < 0.001), subjective norm (ß = 0.311, p < 0.001), perceived behavioral control (ß = 0.162, p < 0.001), and knowledge level (ß = 0.152, p < 0.01) positively predicted primary care physicians' intention to provide CCSSs. Conclusions: TPB model, with the addition of knowledge, was useful in predicting primary care physicians' intention to provide CCSSs for rural Chinese women. The findings of this study provide a reference for the government and hospitals to develop strategies to improve the intent of primary care physicians to provide CCSSs.


Assuntos
Médicos de Atenção Primária , Neoplasias do Colo do Útero , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Intenção , Análise de Classes Latentes , Inquéritos e Questionários , Neoplasias do Colo do Útero/diagnóstico
2.
Int J Oral Sci ; 14(1): 28, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650189

RESUMO

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.


Assuntos
Úlceras Orais , Consenso , Humanos , Úlceras Orais/diagnóstico , Úlceras Orais/etiologia , Úlceras Orais/terapia
3.
Oxid Med Cell Longev ; 2022: 3050007, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651730

RESUMO

Purpose: To observe and compare the efficacy of modified trabeculectomy (TE), Ahmed drainage valve implantation (AGV), and EX-PRESS glaucoma shunt for refractory glaucoma (RG). Methods: The study population of this retrospective study comprised 73 patients (76 eyes) who were suffering from RG and treated with modified TE, AGV, and EX-PRESS glaucoma shunt in our hospital from October 2012 to October 2020. The number of cases who underwent modified TE, AVG, and EX-PRESS glaucoma shunt was 36 (38 eyes). 19 (20 eyes), and 18 patients (18 eyes), respectively. The intraocular pressure (IOP), best-corrected visual acuity (BCVA), postoperative antiglaucoma medications, filter bubble morphology, anterior chamber depth (ACD), successful rate, and postoperative complications were recorded and statistically analyzed preoperative and 1 d, 1 w, 1 mon, 3 mon, 6 mon, and the end follow-up after operation. Results: The BCVA differed insignificantly among the three cohorts before and 6 months after surgery. Compared to preoperative BCVA, the postoperative BCVA of the three groups had no statistical significance. An obvious reduction in IOP was observed in all the three group after operation (P < 0.05). An obvious decrease in antiglaucoma medications was observed after surgery in all the three groups (P < 0.05). The AGV group showed deeper ACD postoperatively, while no marked difference was found in postoperative ACD in the other two groups. The total success rates in modified TE and AGV groups were slightly higher than those in the EX-PRESS group. The three groups differed insignificantly in filter bubble morphology after operation. Conclusion: Modified TE, AGV, and EX-PRESS glaucoma shunt showed equivalent efficacy for RG, which could validly reduce IOP and postoperative antiglaucoma medications. However, the success rates of modified TE and AGV were slightly higher than those of EX-PRESS glaucoma shunt in the last follow-up, and their complications were slightly less than those of the EX-PRESS glaucoma shunt.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma , Trabeculectomia , Glaucoma/cirurgia , Humanos , Estudos Retrospectivos , Tonometria Ocular
4.
Biomed Res Int ; 2022: 6180349, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669730

RESUMO

This work aims at investigating the protective effects of the mitochondria-targeted peptide SS31, on mitochondria function, preventing human retinal pigment epithelial cell-19 (ARPE-19) cell apoptosis. The ARPE-19 cells were subjected to 24 h of intervention with H2O2 of various concentrations (0, 100, 150, 200, 250, 300, and 500 µmol/L). Various concentrations of SS31 (10 nM, 100 nM, and 1 µmol/L) pretreated the cells for 2 h. The MTT assay determined cell viability. ARPE-19 cell apoptosis was observed by 4',6-diamidino-2-phenylindole (DAPI) staining under fluorescence microscope and detected by Annexin-V/PI staining under flow cytometry. The measurement of reactive oxygen species (ROS) release level used MitoSOX Red (a mitochondrial superoxide indicator) and the probe 2'-7'dichlorofluorescin diacetate (DCFH-DA). And with the use of a JC-1 probe, the mitochondrial membrane potential (MMP; ΔΨm) was analyzed. Reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR were responsible for measuring the levels of apoptosis related genes (Bcl-2, Bax, and Caspase-3). The cell viability increased significantly with SS31 pretreated (P < 0.05). In the SS31 + H2O2 group, the fluorescence of the cell nuclei with DAPI staining was weaker than H2O2 along group accordance with the decreased ratio of apoptotic cells (P < 0.05). The ROS generation decreased in SS31 pretreated group, with the increased ΔΨm. The RT-PCR result showed decreased Bax gene and Caspase-3 gene expression with SS31 pretreatment, while increased antiapoptotic gene Bcl-2 (P < 0.05). We provide evidence that SS31 promotes resilience of RPE cells to oxidative stress by stabilizing mitochondrial function.


Assuntos
Antioxidantes , Peróxido de Hidrogênio , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose , Caspase 3/metabolismo , Sobrevivência Celular , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Mitocôndrias/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
5.
Turk J Haematol ; 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35658330

RESUMO

Objectives: Accumulating evidence indicated that miRNAs can negatively influence the expression of their downstream genes, thereby affecting the development of human cancers. The pathogenesis of acute lymphoblastic leukemia (ALL) is complex, and more biomarkers and functional molecules need to be found. Methods: Bioinformatics analyses were performed to screen out the differentially expressed miRNAs in ALL and determine the research subject. qRT-PCR and Western blot were applied to evaluate the expression levels of target genes. Cell functional experiments and mouse experiments were conducted to analyze the roles of target genes in ALL. Results: MiRNA-181b-5p was highly and differentially expressed in ALL and may target SSX2IP. The up-regulation of miRNA-181b-5p and down-regulation of SSX2IP were observed in ALL cells. MiRNA-181b-5p could control multiple pathological processes of ALL, including cell proliferation, migration, cell cycle and apoptosis, and that miRNA-181b-5p could facilitate tumor growth in vivo. Conclusion: MiRNA-181b-5p promoted the malignant progression of ALL by downregulating SSX2IP. miRNA-181b-5p/SSX2IP axis may be a promising target for intervention of malignant behaviors of ALL.

6.
Pharmacol Res ; 182: 106285, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35662627

RESUMO

Vinigrol is a natural diterpenoid with unprecedented chemical structure, driving great efforts into its total synthesis in the past decades. Despite anti-hypertension and anti-clot ever reported, comprehensive investigations on bioactions and molecular mechanisms of Vinigrol are entirely missing. Here we firstly carried out a complete functional prediction of Vinigrol using a transcriptome-based strategy coupled with multiple bioinformatic analyses and identified "anti-cancer" as the most prominent biofunction ahead of anti-hypertension and anti-depression/psychosis. Broad cytotoxicity was subsequently confirmed on multiple cancer types. Further mechanistic investigation on several breast cancer cells revealed that its anti-cancer effect was mainly through activating PERK/eIF2α arm of unfolded protein response (UPR) and subsequent non-apoptotic cell death independent of caspase activities. The other two branches of UPR, IRE1α and ATF6, were functionally irrelevant to Vinigrol-induced cell death. Using CRISPR/Cas9-based gene activation, repression, and knockout systems, we identified the essential contribution of ATF4 and DDIT3, not ATF6, to the death process. This study unraveled a broad anti-cancer function of Vinigrol and its underlying targets and regulatory mechanisms. It paved the way for further inspection on the structure-efficacy relationship of the whole compound family, making them a novel cluster of PERK-specific stress activators for experimental and clinical uses.

7.
Health Qual Life Outcomes ; 20(1): 98, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725609

RESUMO

PURPOSE: Mapping the Minnesota Living with Heart Failure Questionnaire (MLHFQ) to SF-6Dv2 in Chinese patients with chronic heart failure, and to obtain the health utility value for health economic assessment. METHODS: Four statistical algorithms, including ordinary least square method (OLS), Tobit model, robust MM estimator (MM) and censored least absolute deviations (CLAD), were used to establish the alternative model. Models were validated by using a tenfold cross-validation technique. The mean absolute error (MAE) and root mean square error (RMSE) were used to evaluate the prediction performance of the model. The Spearman correlation coefficient and Intraclass Correlation Coefficients (ICC) were used to examine the relationship between the predicted and observed SF-6Dv2 values. RESULTS: A total of 195 patients with chronic heart failure were recruited from 3 general hospitals in Beijing. The MLHFQ summary score and domain scores of the study sample were negatively correlated with SF-6Dv2 health utility value. The OLS regression model established based on the MLHFQ domain scores was the optimal fitting model and the predicted value was highly positively correlated with the observed value. CONCLUSION: The MLHFQ can be mapped to SF-6Dv2 by OLS, which can be used for health economic assessment of cardiovascular diseases such as chronic heart failure.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , China , Doença Crônica , Humanos , Análise dos Mínimos Quadrados , Inquéritos e Questionários
8.
Emerg Med Int ; 2022: 3112281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721255

RESUMO

Objective: To detect EGFR/KRAS genes in pleural effusion cell-free DNA in patients with advanced non-small-cell lung cancer (NSCLC) and to explore the clinical significance of EGFR/KRAS mutation status in pleural effusion. Methods: A retrospective collection was performed on the specimens of pleural effusion and matched tissues from 50 patients with advanced NSCLC admitted to the hospital between January 2019 and January 2021. DNA mutation status of EGFR/KRAS in different specimens was detected and compared by pyrosequencing. The clinicopathological data and follow-up data of survival were collected. The relationship between DNA mutation and clinicopathological characteristics and prognosis was analyzed. Results: In the 50 pleural effusion specimens, there were 22 cases (44.00%) with EGFR mutations (19/21 exon mutations), including 12 cases with EGFR19 deletion mutation and 10 cases with EGFR21 exon L858R mutation. There were 6 cases (12.00%) with KRAS mutations (single-base substitution mutations), including 4 cases with 12-codon mutation and 2 cases with 13-codon mutation. In the 50 tissue specimens, there were 24 cases (48.00%) with EGFR mutations and 4 cases (8.00%) with KRAS mutations. There was no significant difference between pleural effusion specimens and tissue specimens, with good consistency (kappa = 0.920-0.779, P > 0.05). EGFR mutation in pleural effusion was related to smoking history, types of pathological tissues, and lymph node metastasis (P < 0.05). The incidence of EGFR mutation was higher in nonsmokers, patients with lung adenocarcinoma, and patients with lymph node metastasis. The carcinoembryonic antigen (CEA) in patients with EGFR mutation was higher than that with wild-type EGFR, while the level of cytokeratin 19 fragment (Cy21-1) was lower than that with wild-type EGFR (P < 0.05). The 1-year overall survival rate in the EGFR mutation group was significantly higher than that in the EGFR wild group (68.18% vs. 42.86%) (HR = 0.419, 95% CI = 0.178-0.989, and P < 0.001). Conclusion: For the detection of EGFR gene mutation, the results of the pleural effusion specimens and the tumor pathological tissue specimens were well consistent and the detection of pleural effusion could be used as an alternative method when tissue specimens cannot be obtained. EGFR gene mutations are present in majority in patients with advanced NSCLC. The incidence of EGFR mutation is higher in nonsmokers, patients with lung adenocarcinoma, those with lymph node metastasis, those with high-expression CEA, and those with low-expression Cy21-1. The prognosis is better in patients with EGFR mutation.

9.
Front Cardiovasc Med ; 9: 895167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722108

RESUMO

Background: The healing response of the Firehawk stent in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. Aim: We compared the vascular healing of a biodegradable polymer sirolimus-eluting stent (Firehawk) vs. a durable polymer everolimus-eluting stent (Xience) at 6 months after percutaneous coronary intervention (PCI) in patients with STEMI. Methods: In this prospective, multicenter, randomized, non-inferiority study, patients within 12 h of STEMI onset were randomized in a ratio of 1:1 to receive Firehawk or Xience stents. Optical coherence tomography (OCT) follow-up was performed 6 months after the index procedure and assessed frame by frame. The primary endpoint was the neointimal thickness (NIT) at 6 months evaluated by OCT. The safety endpoint was target lesion failure (TLF) at 12 months. Results: The Firehawk stent was non-inferior to the Xience stent in terms of the neointimal thickness (73.03 ± 33.30 µm vs. 78.96 ± 33.29 µm; absolute difference: -5.94 [one-sided 95% lower confidence bound: -23.09]; P non-inferiority < 0.001). No significant difference was observed between the Firehawk and Xience groups regarding the percentage of uncovered struts (0.55 [0.08, 1.32]% vs. 0.40 [0.21, 1.19]%, P = 0.804), the percentage of malapposed struts (0.17 [0.00, 1.52]% vs. 0.17 [0.00, 0.69]%, P = 0.662), and the healing score (1.56 [0.23, 5.74] vs. 2.12 [0.91, 3.81], P = 0.647). At 12 months, one patient in the Firehawk group experienced a clinically indicated target lesion revascularization. No other TLF events occurred in both groups. Independent risk factors of the NIT included body mass index, hyperlipidemia, B2/C lesions, thrombus G3-G5, thrombus aspiration, and postdilation pressure. Conclusion: In patients with STEMI, Firehawk was non-inferior to Xience in vascular healing at 6 months. Both stents exhibited nearly complete strut coverage, moderate neointimal formation, and minimal strut malapposition. Clinical Trial Number: NCT04150016.

10.
Artigo em Inglês | MEDLINE | ID: mdl-35731775

RESUMO

The Area Under the ROC Curve (AUC) is a crucial metric for machine learning, which evaluates the average performance over all possible True Positive Rates (TPRs) and False Positive Rates (FPRs). Based on the knowledge that a skillful classifier should simultaneously embrace a high TPR and a low FPR, we turn to study a more general variant called Two-way Partial AUC (TPAUC), where only the region with TPR ≥ α, FPR ≤ ß is included in the area. Moreover, a recent work shows that the TPAUC is essentially inconsistent with the existing Partial AUC metrics where only the FPR range is restricted, opening a new problem to seek solutions to leverage high TPAUC. Motivated by this, we present the first trial in this paper to optimize this new metric. The critical challenge along this course lies in the difficulty of performing gradient-based optimization with end-to-end stochastic training, even with a proper choice of surrogate loss. To address this issue, we propose a generic framework to construct surrogate optimization problems, which supports efficient end-to-end training with deep learning. Moreover, our theoretical analyses show that: 1) the objective function of the surrogate problems will achieve an upper bound of the original problem under mild conditions, and 2) optimizing the surrogate problems leads to good generalization performance in terms of TPAUC with a high probability. Finally, empirical studies over several benchmark datasets speak to the efficacy of our framework.

11.
J Photochem Photobiol B ; 233: 112481, 2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35660310

RESUMO

AYAPE (Ala-Tyr-Ala-Pro-Glu) is a pentapeptide isolated from Isochrysis zhanjiangensis, previous studies have proved that this pentapeptide has antioxidant and inflammatory activities. In this study, we determined the anti-skin aging bioactivity of AYAPE with UVB-induced human immortalized keratinocytes (HaCaT) and H2O2-induced human skin fibroblasts (BJ cells) as models. The results showed that AYAPE against UVB-induced photoaging on HaCaT cells via alleviating DNA damage, reducing intracellular reactive oxygen (ROS) levels, down regulating phosphorylation of proteins in MAPK/AP-1 signaling pathways. In addition, AYAPE attenuated senescence related effectors expression in H2O2-induced BJ cells. Furthermore, p53 showed an important role in regulation effect of AYAPE in both two cells, and AYAPE showed a directly combination with p53 by molecular docking. These results demonstrated that AYAPE is potential to against skin aging by decreasing matrix metalloproteinase-1 (MMP-1) production, inhibiting inflammation and apoptosis, and attenuating fibroblast senescence.

12.
J Oncol ; 2022: 6425133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35669240

RESUMO

Objectives: This study aimed to observe the relationship among heavy metals concentration, microsatellite instability (MSI), and human epidermal growth factor receptor type 2 (HER2) gene amplification in gastric cancer (GC) patients. Methods: The concentrations of 18 heavy metals in the plasma of GC patients and healthy controls were measured by inductive coupled plasma emission spectrometry (ICP-MS). MSI detection was conducted by detecting 5 microsatellite repeat markers by PCR analysis. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH). The relationship among heavy metal elements, tumor biomarkers, HER2 amplification, and MSI status was analyzed by Pearson correlation analysis. Results: A total of 105 GC patients and 62 healthy controls were recruited in this study. The concentration of arsenic (As), chromium (Cr), cuprum (Cu), mercury (Hg), manganese (Mn), lead (Pb), stibium (Sb), selenium (Se), stannum (Sn), strontium (Sr), thallium (Tl), vanadium (V), and zinc (Zn) were significantly different between GC patients and controls. Among 105 GC patients, including 87 microsatellite-stable (MSS) samples and 18 MSI samples, the concentration of Ga is significantly higher in the MSI group than that in the MSS group. Meanwhile, in 97 GC patients having detected HER2 gene amplification, 69 of 97 had negative HER2 gene amplification and the rest 28 GC patients had positive HER2 gene amplification. The concentration of Hg, Sn, and Tl is noticeably higher in the HER2 positive group than in the HER2 negative group. Only Sb was positively correlated with MSI, but none of these heavy metals was correlated with HER2 gene amplification. Conclusions: The results indicated that Sb has significant positive correlation with the MSI status, which suggests that Sb may cause MSI in GC. However, further research studies are required to elucidate the mechanisms in the near feature.

13.
Biochem Biophys Res Commun ; 612: 91-98, 2022 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-35512462

RESUMO

Nephrotoxicity is a major adverse reaction of cisplatin-based chemotherapy. Organic cation transporter 2 (OCT2) which is located on the basement membrane of human proximal renal tubules is responsible for the renal accumulation of cisplatin and its nephrotoxicity. This study aimed to investigate the protective effect of PPIs to CP-induced nephrotoxicity. Three kinds of PPIs including lansoprazole, omeprazole and rabeprazole (Rab) were co-administrated with CP to mice. In addition, OCT2-overexpressed HEK293, HK-2 and A549 cells were co-incubated with CP and PPIs. The results showed that PPIs can attenuate CP-induced increase of CRE, BUN and histological damage of kidney. Among the three PPIs, Rab was found with a superior protective effect. It significantly reduced the accumulation of CP in OCT2-overexpressed HEK293 cells and in the renal cortex tissues of mice, but not in HK-2 cells. Moreover, Rab reduced the expression levels of cleaved-caspase-3, RIPK1, RIPK3, MLKL and p-MLKL and the apoptosis rate of renal tubular cells induced by CP in vivo, but not in HK-2 cells. However, Rab increased the viability of CP-treated cells in a concentration-dependent manner and attenuated CP-induced apoptosis and necroptosis in OCT2 over-expressed HEK293 cells. Finally, we demonstrated that Rab have no influence on the antitumor effect of CP. In conclusion, Rab attenuate CP-induced nephrotoxicity mainly through inhibiting OCT2-mediated CP uptake, without interfering with its anti-tumor property of inducing apoptosis and necroptosis.


Assuntos
Injúria Renal Aguda , Antineoplásicos , Injúria Renal Aguda/patologia , Animais , Antineoplásicos/farmacologia , Apoptose , Cisplatino/efeitos adversos , Células HEK293 , Humanos , Rim/metabolismo , Camundongos , Necroptose , Rabeprazol/efeitos adversos
14.
Chem Commun (Camb) ; 58(47): 6733-6736, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35604320

RESUMO

An unprecedented deoxygenative gem-difluorovinylation of aliphatic alcohols using α-trifluoromethyl alkenes is achieved under photocatalytic conditions. Inexpensive Ph3P acts as an efficient O-atom transfer reagent to facilitate the deoxygenation of alcohols for the generation of reactive alkyl radical species. Remarkable features of this reaction include mild conditions, simple operation and broad scope. The synthetic utility of this reaction was validated by the success of two-step one-pot reactions, scale-up synthesis and chemoselective monodeoxygenation of diols.


Assuntos
Álcoois , Alcenos , Catálise , Estrutura Molecular
15.
ACS Chem Neurosci ; 13(12): 1697-1713, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35607807

RESUMO

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder featured by memory loss and cognitive default. However, there has been no effective therapeutic approach to prevent the development of AD and the available therapies are only to alleviate some symptoms with limited efficacy and severe side effects. Necroptosis is a new kind of cell death, being regarded as a genetically programmed and regulated pattern of necrosis. Increasing evidence reveals that necroptosis is tightly related to the occurrence and development of AD. This review aims to summarize the potential role of necroptosis in AD progression and the therapeutic capacity of targeting necroptosis for AD patients.


Assuntos
Doença de Alzheimer , Necroptose , Doença de Alzheimer/tratamento farmacológico , Apoptose , Humanos , Necrose , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-35579574

RESUMO

Necroptosis, a form of inflammation-related programmed cell death, is a major mechanism of proximal tubular cell injury in acute kidney injury (AKI). Blockade of necroptosis signaling represents a promising strategy for clinical therapy of AKI. Previously, we identified a small molecular RIPK1 inhibitor Cpd-71 with nephroprotective activities. In order to discover more nephroprotective agents, in this study, twenty chalcone derivatives were synthesized and evaluated for their anti-necroptosis and nephroprotective activities. Among the chalcone derivatives, Cpd-2 exhibited the most potent anti-necroptosis activity (IC50 = 1.08 µM) and protective activity (EC50 = 1.49 µM) through directly binding to RIPK1 and blocking RIPK1-RIPK3-MLKL signaling pathway. Furthermore, Cpd-2 effectively attenuated cisplatin or hypoxia/reoxygenation (H/R)-induced injury and necroptotic inflammation in renal cell models. Moreover, in cisplatin- or ischemia/reperfusion (I/R) induced AKI mouse model, detection of creatinine and urea nitrogen in blood showed that Cpd-2 improved kidney function. PAS staining and immunofluorescence analysis indicated that Cpd-2 also reduced pathological damage and inhibited inflammatory development in kidney tissues. In summary, although some chalcone derivatives have been reported to prevent kidney injury previously, our present study not only discovered a promising leading compound Cpd-2, but also provided a novel and successful practice for the development of necroptosis inhibitors from natural products derivatives as AKI therapeutic agents. This article is protected by copyright. All rights reserved.

18.
Oxid Med Cell Longev ; 2022: 2496649, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535356

RESUMO

Objective: To observe the outcomes of cataract surgery in ocular cicatricial pemphigoid (OCP) patients and explore routine perioperative medical treatments. Design: Retrospective case series. Methods: Fourteen eyes of 8 patients were included in the study. Foster's stage 1-4 OCP patients were given human intravenous immunoglobulin, whereas patients with active inflammation were treated with prednisone tablets and methotrexate. Those who were intolerant to methotrexate and had severe inflammatory symptoms were treated with cyclophosphamide. Cataract surgery was performed for all patients after three months of systemic treatment under stable conditions. The conjunctival biopsy was evaluated by immunofluorescence microscopy. Then, patients were divided into individuals with or without ankyloblepharon. Records were reviewed for OCP stage, type of surgery, best-corrected visual acuity (BCVA), Schirmer I test, corneal fluorescein sodium staining, meibomian gland coloboma range, and ocular surface disease index (OSDI) scores. Follow-up was for the duration of taking topical and systemic medication. Results: Nine female (64.29%) and 4 male (35.71%) eyes were diagnosed with OCP by biopsy. The mean follow-up time was 60.64 ± 35.62 months. Thirteen eyes (92.86%) of 7 patients underwent phacoemulsification. One eye underwent phacoemulsification combined with amniotic membrane transplantation. The intracapsular extraction of cataract was applied to one eye. The BCVA improved significantly in all the patients, which remained stable until the last follow-up. The Schirmer I test was higher than that before the surgery. Corneal fluorescein sodium staining after surgery showed a decrease in score compared to the preoperative score. The BCVA of the patients after surgery increased significantly. The OSDI scores of patients with ankyloblepharon were significantly higher than for those without it. Postoperative symblepharon showed no significant difference compared to the preoperative symblepharon. Conclusions: In this series, OCP patients with cataracts were able to undergo phacoemulsification surgery, whereas routine use of immunosuppression and closed postoperative follow-up were necessary.


Assuntos
Catarata , Penfigoide Mucomembranoso Benigno , Feminino , Fluoresceína/uso terapêutico , Humanos , Masculino , Metotrexato , Penfigoide Mucomembranoso Benigno/diagnóstico , Penfigoide Mucomembranoso Benigno/tratamento farmacológico , Estudos Retrospectivos , Acuidade Visual
19.
Therap Adv Gastroenterol ; 15: 17562848221098246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601804

RESUMO

Background: Raltitrexed plus S-1 (RS) and regorafenib both showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. This study aims to compare the effectiveness and safety of two different regimens in patients with refractory mCRC. Methods: This retrospective cohort study included mCRC patients who were treated with RS or regorafenib from February 2017 to June 2021. A propensity score matching (PSM) analysis was conducted to balance the baseline characteristics of all patients. Progression-free survival (PFS), overall survival (OS), tumor response, and safety of two regimens were evaluated. Results: A total of 187 patients were included in our study, with 107 patients in the RS group and 80 patients in the regorafenib group. After PSM, 78 pairs were recognized. Patients treated with RS had a semblable PFS compared to those treated with regorafenib before PSM (4.8 months vs 5.5 months, p = 0.400) and after PSM (4.7 months vs 5.4 months, p = 0.430). Patients in the RS group were associated with a longer OS than those in the regorafenib group (13.4 months vs 10.1 months, p = 0.010). A similar trend of OS was also obtained in the matched cohort (13.3 months vs 10.0 months, p = 0.024). Both objective response rate (12.8% vs 5.1%, p = 0.093) and disease control rate (53.8% vs 46.2%, p = 0.337) in the RS cohort were higher than those in the regorafenib group, without significant differences. Adverse events (AEs) of each group were well tolerated. Conclusion: Patients treated with RS demonstrated a longer OS than those treated with regorafenib and had manageable AEs, which could be recognized as a primary choice for refractory mCRC. Plain Language Summary: Efficacy and Safety of Raltitrexed plus S-1 Versus Regorafenib in Patients with Refractory Metastatic Colorectal Cancer: A Real-world Propensity Score Matching StudyBoth raltitrexed plus S-1 (RS) and regorafenib showed considerable efficacy for metastatic colorectal cancer (mCRC) patients. No study has compared the two regimens yet. Therefore, we compare the efficacy and safety between RS and regorafenib to provide an optimal treatment option. We retrospectively included patients with mCRC who failed at least two standard treatments. All enrolled patients received RS or regorafenib treatments. We conducted a propensity score matching to eliminate differences in the enrolled patients. After the analysis, we found no significant differences in progression-free survival in patients between the two groups. However, patients treated with RS had a longer OS than those treated with regorafenib, whether before matching (13.4 months vs 10.1 months, p = 0.010) or after matching (13.3 months vs 10.0 months, p = 0.024). In addition, the adverse effects caused by cancer-related therapy were tolerable for the patient. Certainly, this is a non-randomized retrospective study with a small sample size, so we conducted a propensity score matching to minimize potential bias. Importantly, this is the first research comparing the two treatments, and we believe that the results of this article could present a primary choice for clinical doctors dealing with patients with standard treatments that failed mCRC.

20.
Clin Exp Immunol ; 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35605143

RESUMO

Oral lichen planus (OLP) is a common chronic inflammatory disease occurring in the oral mucosa. Bacteria is a key driver of mucosal immune response and can induce changes in gene expression and function of epithelial keratinocytes. IL-36γ can induce the expression of antimicrobial peptides, cytokines and chemokines, and is widely involved in many chronic inflammatory diseases. Our aim is to explore the role of IL-36γ in pathological process of OLP when Prevotella melaninogenica (P. melaninogenica) invades oral mucosa. The expression of IL-36γ in OLP lesions and mice was detected by immunohistochemistry. Recombinant human IL-36Gamma (rhIL-36γ) was used to treat oral keratinocytes and the expression levels of inflammatory cytokines were detected by qRT-PCR and ELISA. The expression of IL-36γ and TRPV1 was detected by western blotting following co-culturing P. melaninogenica with oral keratinocytes. The mRNA expression of IL-36γ was detected by qRT-PCR. From our results, IL-36γ was upregulated in OLP lesions. Exogenous rhIL-36γ promoted the expression of pro-inflammatory cytokines and antibacterial peptides in oral keratinocytes. The expression of IL-36γ was significantly increased following the stimulation of P. melaninogenica in oral keratinocytes and mice. TRPV1 activation was induced by P. melaninogenica and its activation enhanced the expression of IL-36γ. IL-36Ra could reduce the inflammation in OLP in vitro. In summary, overexpression of IL-36γ in OLP lesions could promote its pathogenesis by inducing inflammation. P. melaninogenica invasion of oral keratinocytes could induce the expression of IL-36γ by the activation of TRPV1, thereby regulating the interaction between bacteria and oral epithelial cells.

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