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Objective:To test the hypothesis that Pertussis toxin (PTX) can promote the occurrence of interstitial lung disease (ILD) in experimental autoimmune myositis (EAM) model and clarify the potential pathogenic mechanism.Methods:EAM mice model were induced by Skeletal muscle thomogenate with or without PTX, and the relationship between ILD phenotypes and neutrophil extracellular traps (NETs) infiltration was analyzed by histopathological and serological studies in EAM with PTX group and EAM without PTX group. Healthy mice were given PTX alone intraperitoneally to clarify whether NETs formation could be induced in vivo, and neutrophils separated from healthy human blood were intervened with PTX to induce NETs formation in vitro. The data was tested for normality using Shapiro-Wilk. Statistical methods and were analyzed using t-test or ANOVA, and multiple comparisons between different groups were tested using Tukey test. Results:Compared with EAM without PTX group, lung tissues in EAM with PTX group had multiple pathological changes similar to polymyositis/dermatomyositis-related ILD. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the main pathological types. The pulmonary interstitial lesions were accompanied by significant infiltration of NETs; and serum NETs markers levels were obviously elevated in EAM with PTX group, compared with the control group [ n=5, (87±10) ng/ml], cfDNA levels were statistically significantly elevated in both the EAM without PTX group [ n=4, (115±27) ng/ml] and the EAM with PTX group [ n=7, (150±50) ng/ml] ( F=4.24, P=0.038); Cit-H3-DNA levels were elevated in the EAM without PTX group ( n=4, 0.24±0.09), and in the EAM EAM with PTX group ( n=6, 0.33±0.11) compared with the control group ( n=4, 0.13±0.02) ( F=6.21, P=0.016). After PTX intervention, serum cfDNA levels were higher in the PTX group [ n=3, (100±40) ng/ml] than in the control group [ n=3, (45±12) ng/ml, t=2.27, P=0.086]; PTX also induced neutrophils to form NETs in vitro. Conclusion:PTX may promote the development of ILD in EAM mice model by inducing the formation of NETs, indicating that EAM mice can serve as a model for targeting NETs to study the pathogenesis ILD.
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Biotransformation of ursonic acid (1) by two fungal strains Aspergillus ochraceus CGMCC 3.5324 and Aspergillus oryzae CGMCC 3.407 yielded thirteen new compounds (4, 5, 7-10, and 13-19), along with five recognized ones. The structural details of new compounds were determined through spectroscopic examination (NMR, IR, and HR-MS) and X-ray crystallography. Various modifications, including hydroxylation, epoxidation, lactonization, oxygen introduction, and transmethylation, were identified on the ursane core. Additionally, the anti-neuroinflammatory efficacy of these derivatives was assessed on BV-2 cells affected by lipopolysaccharides. It was observed that certain methoxylated and epoxylated derivatives (10, 16, and 19) showcased enhanced suppressive capabilities, boasting IC50 values of 8.2, 6.9, and 5.3 µM. Such ursonic acid derivatives might emerge as potential primary molecules in addressing neurodegenerative diseases.
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Aspergillus ochraceus , Aspergillus oryzae , Aspergillus ochraceus/química , Cristalografia por Raios X , BiotransformaçãoRESUMO
Citrullus colocynthis (L.) Schrad. (Cucurbitaceae) is widely distributed in the desert areas of the world. The fruit bodies of C. colocynthis are recognized for their wide range of nutraceutical potential, as well as medicinal and pharmaceutical uses. The plant has been reported for various uses, such as asthma, bronchitis, cancer, colic, common cold, cough, diabetes, dysentery, and jaundice. The fruit has been extensively studied for its biological activities, which include insecticide, antitumor, and antidiabetic effects. Numerous bioactive compounds have been reported in its fruit bodies, such as essential oils, fatty acids, glycosides, alkaloids, and flavonoids. Of these, flavonoids or caffeic acid derivatives are the constituents associated with the inhibition of fungal or bacterial growth, whereas eudesmane sesquiterpenes or sesquiterpene lactones are most active against insects, mites, and nematodes. In this review, the scientific evidence for the biological activity of C. colocynthis against insecticide, cytotoxic, and antidiabetic effects is summarized.
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Citrullus colocynthis , Inseticidas , Flavonoides , Hipoglicemiantes/farmacologia , Preparações FarmacêuticasRESUMO
The role of HEV infection in AP remains unclear. 1000 patients with AP and 1000 HCs were enrolled, and pancreatitis was evaluated in HEV-infected rhesus macaques. The positive rates of anti-HEV IgG, IgM, and HEV RNA in the AP patients were significantly higher than HCs. With the increase in the severity of AP, the percentage of HEV infection increased. AP patients were divided into AP- and AP + AHE groups. The percentage of severe AP in the AP + AHE group was significantly higher than in the AP- group. HEV infection was one of the main independent risk factors and had high predictive power for AP outcomes. A high level of HEV titer would prolong the recovery time and increase the risk of recurrent AP. Moreover, AP + AHE patients receiving conservative treatment showed a better prognosis. Furthermore, HEV can replicate in the pancreas of rhesus macaques. The pancreatic islet structure was damaged, the tissue was loose after 272 dpi, and a large amount of hyperemia appeared after 770 dpi. HEV infection also caused a large number of inflammatory cells in the pancreas. The pancreas and liver had a comparable viral load. HEV infection affects AP's occurrence, development, and prognosis.
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Vírus da Hepatite E , Pancreatite , Animais , Humanos , Pancreatite/etiologia , Macaca mulatta/genética , Doença Aguda , Anticorpos Anti-Hepatite/genética , RNA Viral/genética , Vírus da Hepatite E/genética , Genótipo , Imunoglobulina MRESUMO
Hematopoietic stem cells (HSCs) are important for the hematopoietic system because they can self-renew to increase their number and differentiate into all the blood cells. At a steady state, most of the HSCs remain in quiescence to preserve their capacities and protect themselves from damage and exhaustive stress. However, when there are some emergencies, HSCs are activated to start their self-renewal and differentiation. The mTOR signaling pathway has been shown as an important signaling pathway that can regulate the differentiation, self-renewal, and quiescence of HSCs, and many types of molecules can regulate HSCs' these three potentials by influencing the mTOR signaling pathway. Here we review how mTOR signaling pathway regulates HSCs three potentials, and introduce some molecules that can work as the regulator of HSCs' these potentials through the mTOR signaling. Finally, we outline the clinical significance of studying the regulation of HSCs three potentials through the mTOR signaling pathway and make some predictions.
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AIM: To investigate the expression and correlation of C1q/tumor necrosis factor related protein 9(CTRP9)levels in the serum of patients with different stages of diabetic retinopathy(DR)and diabetic macular edema(DME).METHODS: A total of 135 patients with type 2 diabetes who were admitted to Gansu Provincial Hospital from April 2021 to April 2022 were selected as the experimental group. According to the results of non-mydriatic fundus photography, they were divided into non-DR(NDR)group(n=45), non-proliferative DR(NPDR)group(n=45), proliferative DR(PDR)group(n=45); according to the results of optical coherence tomography, DR patients were divided into DME group(n=51), non-DME group(n=39). In addition, other 45 healthy subjects who matched the age and sex of the experimental group were selected as normal control group. The clinical data and biochemical index test results of subjects in each group were recorded and compared, the correlation between serum CTRP9 level and other biochemical indexes was analyzed, and the risk factors affecting the occurrence of DR and DME were explored.RESULTS: There were significant differences in serum CTRP9 levels among subjects in normal control group, NDR group, NPDR group and PDR group(P<0.001), and normal control group > NDR group > NPDR group > PDR group. There was significant difference in serum CTRP9 level between DME group and non-DME group(P<0.001), and non-DME group > DME group. Spearman rank correlation analysis showed that the level of serum CTRP9 in DR patients was negatively correlated with the course of diabetes(rs=-0.251, P<0.05), the level of serum CTRP9 in DME patients was negatively correlated with fasting blood glucose(FBG)(rs=-0.370, P<0.05)and glycosylated hemoglobin(HbA1c)(rs=-0.421, P<0.05). Logistic multivariate regression analysis showed that the course of diabetes(OR=1.194, 95%CI: 1.068~1.335,P=0.002)and the level of serum CTRP9(OR=0.936, 95%CI: 0.907~0.966,P<0.001)were risk factors for DR. The level of serum CTRP9 was a risk factor affecting the occurrence of DME(OR=0.838, 95%CI: 0.778~0.903, P<0.001).CONCLUSION: The reduction of CTRP9 level is a risk factor for the occurrence of DR and DME, which may be of great significance to the risk assessment of both DR and DME.
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Objective To analyze the sequence characteristics of Rhipicephalus microplus Enolase gene, and to predict the secondary and tertiary structure and antigenic epitopes of the Enolase protein. Methods Sixty-two engorged female R. microplus were sampled from a yellow cattle breeding farm in Zhijiang County, Huaihua City, Hunan Province in June 25, 2022. Genomic DNA was isolated from R. microplus, and the Enolase gene was amplified using PCR assay, followed by cloning, sequencing and expression of the amplification product. The sequence characteristics of the Enolase gene were analyzed using the software Clustal X, and the gene sequence was translated into amino acid sequences. The secondary and tertiary structures of the Enolase protein were deduced using the software PRABI, and the physicochemical properties of the Enolase protein were analyzed using the software PRABI. In addition, the B- and T-cell epitopes of the Enolase protein were predicted using the software ABCpred Prediction, Scratch, IEDB and NetCTL. Results The R. microplus Enolase gene sequence was 1 323 bp in size, and the contents of A, T, G and C bases were 24.5%, 22.5%, 27.0% and 26.0%,with 47.0% of A + T content and 53.0% of G + C content. The R. microplus Enolase gene encoded 434 amino acids, and the Enolase protein had a molecular weight of 47.12 kDa. The secondary structure of the Enolase protein contained 186 α-helixes (42.86%), 32 β-turns (7.37%), 144 random coils (33.18%) and 72 extended strands (16.59%). The Enolase protein was most probably present in cytoplasm (76.7%), followed by in mitochondrion (39.1%) and nucleus (21.7%), and the Enolase protein had no signal peptide or transmembrane domain. In addition, the Enolase protein had 14 B-cell dominant epitopes and 8 T-cell dominant epitopes. Conclusions The R. microplus Enolase gene sequence exhibits a GC preference, and its encoding Enolase protein is an acidic and hydrophilic protein, with α-helixes and random coils as its primary structure, and presenting B- and T-cell dominant epitopes, which is a potential target for development of vaccines against R. microplus.
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Purpose/Significance The current situation of internet diagnosis and treatment in medical institutions in Beijing is ana-lyzed and studied to provide references for further promoting internet diagnosis and treatment and improving supervision of internet diagno-sis and treatment in medical institutions.Method/Process By using the methods of literature analysis,questionnaire survey and on-site interview,the current situation of internet diagnosis and treatment in medical institutions that have been qualified for internet diagnosis and treatment in Beijing is investigated.Result/Conclusion The internet diagnosis and treatment has been attached great importance by medical institutions in Beijing and has developed rapidly.However,it is also necessary to further optimize the internal and external envi-ronment for the development of internet diagnosis and treatment,strengthen supervision,and improve the public's acceptance.
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Development of biomarkers for predicting the occurrence of hepatitis E virus related-acute liver failure (HEV-ALF) is conducive to prevention and early intervention. Serum samples from 250 HEV-ALF patients, 250 patients with acute hepatitis E (AHE) and 250 health controls (HCs) were collected. We assessed the predictive ability of extracellular vesicle (EV)-derived argininosuccinate synthase 1 (ASS1) levels for HEV-ALF occurrence. Serum EVs were successfully isolated. EV-derived ASS1 levels in the HEV-ALF patients were significantly higher than those in the AHE patients and HCs. In HEV-ALF patients, EV-derived ASS1 levels were positively correlated with the number of failed organs and disease progression. The logistical regression showed that EV-derived ASS1 level is an independent risk factor for HEV-ALF, and orthogonal partial least squares discriminant analysis (OPLS-DA) also suggested that EV-derived ASS1 level has high predictive capability. Besides, the area under the curve (AUC) of EV-derived ASS1 level to predict HEV-ALF occurrence was 0.728 (0.684-0.772) with the sensitivity and specificity being 72.80% and 64.80%, which had a high decision-making ability. Furthermore, there existed no significant difference between the age ≥60 and age <60 groups in EV-derived ASS1 levels. Serum EV-derived ASS1 level is a promising predictor for the occurrence of HEV-ALF.
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Vesículas Extracelulares , Vírus da Hepatite E , Hepatite E , Falência Hepática Aguda , Humanos , Argininossuccinato Sintase , Hepatite E/diagnóstico , Hepatite E/epidemiologiaRESUMO
Objective:To explore the relationship between marital status and mild cognitive impairment in older adults.Methods:This study is a cluster random sampling.From January to December 2020, a questionnaire survey was conducted among older adults aged 60 years and over in four cities of Hebei Province.Finally, 2690 older adults with mild cognitive impairment and normal cognitive function were enrolled.The older adults were divided into 2 groups according to their marital status: married and living with their spouses(group E1), divorced or living alone(group E2). The mini-mental state examination(MMSE)scores of older adults in the two groups were compared.Moreover, the cognitive differences of older adults between the two groups and the interaction of marital status, social activities and life events on cognitive outcomes were analyzed.Results:The married older adults with partners had better cognitive preservation( P<0.01). The more life events were more likely to cause cognitive impairment( P<0.01), and the interaction of marital status, social activities and life events had a significant impact on cognition( P<0.01). Older men who were married and lived with spouse had better cognition than older women who were married and lived with spouse( P<0.05 in Model 3). The cognition of widowed elderly women was better than those of widowed elderly men( P<0.1 in Model 1; P<0.1 in Model 2). Among elderly men, the cognition of those married and living with spouse was better than that those of widowed( P<0.01 in models 1 and 2, P<0.1 in model 3). Among elderly women, those married and living with spouse had better cognitive outcomes than those widowed( P<0.01 in Model 1, P<0.01 in Model 2). Conclusions:Marital companionship is a protective factor for the cognition of older adults, and there are gender differences in the impact of marital status on cognition in late life.
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【Objective:】 To explore the influencing factors of ethical cognition of intensive care unit (ICU) nursing staff. 【Methods:】 The convenient sampling method was used to select 530 ICU clinical nursing staff from 4 grade A tertiary hospitals in a city from May 2019 to May 2021 as the subjects. Univariate analysis and multivariate analysis were used to determine the influencing factors of ethical cognition of ICU nursing staff. 【Results:】 The results of univariate analysis showed that there were statistically significant differences in ethics committee knowledge scores and research ethics knowledge scores of nursing staff with different education levels, professional titles, attitudes, and training experiences (P<0.05). Among them, nursing staff with a bachelor’s degree or above had a higher total score of ethical cognition than those with a specialized degree or below (P<0.05), the total score of ethical cognition among professor of nursing was higher than that of nurses, nurse practitioners, and nurses-in-charges (P<0.05), the total score of ethical cognition among nursing staff with positive attitudes was higher than that of general positive nursing staff (P<0.05), and the total score of ethical cognition of nurses with training experience was higher than that of those without training experience (P<0.05). The results of multivariate analysis showed that education level, professional title, attitude, and training experience were all influencing factors of the ethical cognition among ICU nursing staff (P<0.05). 【Conclusion:】 Education level, professional title, attitude, and training experience are all influencing factors affecting the ethical cognition of ICU nursing staff, and the above factors should be combined to improve the cognitive ability of ICU nursing staff through multiple ways.
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【Objective:】 To explore the correlation between hospital ethics atmosphere and work engagement of nurses in emergency department, and provide a basis for reasonably solving ethical issues and improving nurses’ work engagement. 【Methods:】 From May 2019 to May 2021, the convenient sampling method was used to select 350 nurses from emergency departments of four tertiary or above hospitals in Xi’an as the research subjects. The Ethical Climate Cognitive Scale and the Work Engagement Scale were used to evaluate the hospital ethical atmosphere and work engagement of nurse, and analyze their correlation. The univariate factor analysis and multiple factor analysis were used to explore the influencing factors. 【Results:】 The work engagement score of emergency department nurses was (51.69±11.09) points, and the ethical atmosphere score was (72.78±11.45) points. The results of univariate analysis showed that there were statistically significant differences in the work engagement scores among emergency department nurses with different educational backgrounds, hospital grades, hospital employment methods, and whether they had received ethics training (P<0.05). The results of multiple factor analysis indicated that the cognition of hospital ethical atmosphere, hospital employment methods, and whether they had received ethics education and training were all factors that affected work engagement (P<0.05). 【Conclusion:】 The hospital ethical atmosphere is positively correlated with the work engagement of emergency department nurse. The ethical atmosphere and work engagement of nurses are both at a moderate level, with significant room for improvement. Therefore, it is necessary to continue to strengthen the management support of emergency nursing work and improve the perceived level of recognition and respect among emergency department nurses in the organization.
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Although the incidence and mortality of lung cancer have decreased significantly in the past decade, it is still one of the leading causes of death, which greatly impairs people's life and health. Proteomics is an emerging technology that involves the application of techniques for identifying and quantifying the overall proteins in cells, tissues and organisms, and can be combined with genomics, transcriptomics to form a multi-omics research model. By comparing the content of proteins between normal and tumor tissues, proteomics can be applied to different clinical aspects like diagnosis, treatment, and prognosis, especially the exploration of disease biomarkers and therapeutic targets. The applications of proteomics have promoted the research on lung cancer. To figure out potential applications of proteomics associated with lung cancer, we summarized the role of proteomics in studies about tumorigenesis, diagnosis, prognosis, treatment and resistance of lung cancer in this review, which will provide guidance for more rational application of proteomics and potential therapeutic strategies of lung cancer.
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Objective: To investigate whether pre-lingual deafness adult caused by inadequate auditory compensation in childhood can benefit from cochlear implants and the related influencing factors. Methods: A total of 26 prelingual deafness as experimental group [11 males and 15 females, the age of operation was (24.5±5.7) years] and 13 postlingual deafness as control group [5 males and 8 females, the age at the time of operation was (42.2±11.4) years] were recruited. Objective assessment included hearing threshold and speech recognition rate tests while wearing cochlear implants. Subjective assessment used Nijmegen Cochlear Implant Questionnaire to assess hearing-related quality of life of subjects. The changes of hearing ability in the prelingual deafness group before and after operation and the differences with the postlingual deafness group were compared, and the correlation between speech recognition ability and the age diagnosed as severe or profound deafness, the age of hearing aid invalid, and duration of wearing cochlear implant were analyzed as factor indicators. All statistical results were analyzed by SAS 9.4 software. Results: In terms of objective indicators, the speech recognition rate of pre-lingual deafness was significantly lower than that of post-lingual deafness [(35.4±28.0)% vs (80.9±8.0)%,t=7.67, P<0.001], while there was no statistical difference in hearing threshold between the two groups [(34.8±4.0) dB HL vs (33.1±3.7) dB HL, t=1.30, P>0.05]. The indicators in the subjective questionnaire showed that the prelingual deafness group was only weaker in advanced sound perception, confidence and total mean score than the post-lingual deafness group (P<0.05), and there was no significant difference in other aspects(P>0.05), meanwhile, all indicators of the prelingual deafness group were significantly improved compared with the preoperative level (P<0.001). There was a moderate positive correlation between the hearing quality and the speech recognition rate in the prelingual deafness group(r=0.51, P=0.008). The regression analysis showed that the invalid age of hearing aid was the exact influencing factor of speech recognition rate. Conclusions: Certain prelingual deaf adults can adapt to cochlear implants and obtain different degrees of auditory assistance. Compared with the improvement of objective auditory ability assessment, the patient who received cochlear implantation gain more improvement in auditory related quality of life subjectively. The ineffective age of preoperative hearing aid is an important factor, which needs to be aroused sufficient preoperative attention.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Implante Coclear/métodos , Implantes Cocleares , Surdez/reabilitação , Qualidade de Vida , Percepção da FalaRESUMO
The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.
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【Objective】 To explore the potential biomarkers and related enrichment pathways of dilated cardiomyopathy (DCM) by bioinformatics methods. 【Methods】 The data sets related to DCM in GEO database were searched, and microarray data sets GSE42955 and GSE1869 of human cardiomyocytes were extracted. Then, the differentially expressed genes (DEGS) were analyzed using R language, and the protein-protein interaction network was analyzed to identify the core genes and core modules of differential expression. The gene ontology database (GO) enrichment and Kyoto Gene and Genome Encyclopedia (KEGG) pathway analyses were performed. The data sets related to DCM in ArrayExpress database were searched, and the human cardiomyocytes microarray data set E-TABM-480 was extracted to verify the expressions of core genes and modules. 【Results】 We identified 10 DEGS, namely, DZIP3, FBXO32, BTBD6, FBXL5, ASB8, COMMD1, LTN1, FBXO21, RCHY1 and ARIH2, and the core DEG was DZIP3. After GO and KEGG analyses, the GO and KEGG of the above DEGS were mainly related to the ubiquitin-proteasome system. 【Conclusion】 Bioinformatics analysis shows that the ubiquitin-proteasome system plays an important role in the pathogenesis of DCM, and the mechanism remains to be further studied.
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Amorphization is one of the most effective pharmaceutical approaches to enhance the dissolution and oral bioavailability of poorly water-soluble drugs. In recent years, amorphous formulations have been experiencing rapid development both in theoretical and practical application. Based on using different types of stabilizing agents, amorphous formulations can be mainly classified as polymer-based amorphous solid dispersion, coamorphous formulation, mesoporous silica-based amorphous formulation, etc. This paper summarizes recent advances in the dissolution and supersaturation of these amorphous formulations. Moreover, we also highlight the roles of stabilizing agents such as polymers, low molecular weight co-formers, and mesoporous silica. Maintaining supersaturation in solution is a key factor for the enhancement of dissolution profile and oral bioavailability, and thus, the strategies and challenges for maintaining supersaturation are also discussed. With an in-depth understanding of the inherent mechanisms of dissolution behaviors, the design of amorphous pharmaceutical formulations will become more scientific and reasonable, leading to vigorous development of commercial amorphous drug products.
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Polímeros , Água , Disponibilidade Biológica , Excipientes , SolubilidadeRESUMO
OBJECTIVE: To evaluate plasma exosome-derived SUMO-specific protease (SENP)1 levels and assess their prognostic value in melanoma. PATIENTS AND METHODS: We extracted exosomes from the plasma of 126 melanoma patients, and identified them with transmission electron microscopy, nanoparticle tracking analysis and western blotting. The plasma exosome-derived SENP1 levels of melanoma patients and healthy controls were detected with ELISA. RESULTS: Plasma exosome-derived SENP1 levels in melanoma patients were significantly upregulated than in healthy controls (P < 0.001). Plasma exosome-derived SENP1 levels in melanoma patients with tumor size >10 cm, located in the mucosa or viscera, with Clark level IV/V, with lymph node metastasis, and TNM stages IIb-IV were significantly higher than in patients in with tumor size <10 cm, located in the skin, with Clark level I-III, without lymph node metastasis, and TNM stages IIb-IV (all P < 0.05). Disease-free survival (DFS) and overall survival (OS) were worse in melanoma patients who had higher plasma exosome-derived SENP1 levels than lower plasma exosome-derived SENP1 levels (both P < 0.001). Area under the receiver operating characteristic curve (AUROC) of plasma exosome-derived SENP1 for predicting 3-year DFS of melanoma patients was 0.82 [95% confidence interval (CI): 0.74-0.88], with a sensitivity of 81.2% (95% CI: 69.9-89.6%) and specificity of 75.4% (95% CI: 62.2-85.9%). The AUROC of plasma exosome-derived SENP1 for predicting 3-year OS of melanoma patients was 0.76 (95% CI: 0.67-0.83), with a sensitivity of 95.7% (95% CI: 85.5-99.5%) and specificity of 62.0% (95% CI: 50.4-72.7%). CONCLUSIONS: Melanoma patients with higher plasma exosome-derived SENP1 levels had worse DFS and OS. The plasma exosome-derived SENP1 levels may be a potential prognostic predictor for 3-year DFS and 3-year OS of melanoma.
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Hepatitis E virus (HEV) is a common cause of viral hepatitis in developing countries, most commonly transmitted through the fecal-oral route. The virus is mainly of genotypes (GT) 1 and GT2 genotypes, and patients usually show symptoms of acute hepatitis. Due to the rising trend of HEV serological prevalence in global population, HEV has become an important public health problem in developed countries. Severe hepatitis caused by HEV includes acute and chronic liver failure (ACLF). ACLF frequently occurs in developed countries and is caused by overlapping chronic liver diseases of HEV with genotypes GT3 and GT4. Because the onset of hepatitis E is closely associated with immunity, it is critical to understand the immunological mechanism of hepatitis E associated with acute and chronic liver failure (HEV-ACLF). This review discusses the immunological manifestations and mechanisms of HEV-ACLF, intrahepatic immune microenvironment and treatment, and raises outstanding questions about the immunological mechanism and treatment of the disease.
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Farnesoid X receptor (FXR) has been considered as an attractive target for metabolic disorder and liver injury, while many current FXR agonists suffer from undesirable side effects, such as pruritus. Therefore, it is urgent to develop new structure types different from current FXR agonists. In this study, a series of structural optimizations were introduced to displace the unstable coumarin and geraniol scaffolds of auraptene (AUR), a novel and safe FXR agonist. All of these efforts led to the identification of compound 14, a potent FXR agonist with nearly fourfold higher activity than AUR. Molecular modeling study suggested that compound 14 fitted well with binding pocket, and formed the key ionic bond with His291 and Arg328. In acetaminophen-induced acute liver injury model, compound 14 exerts better therapeutic effect than that of AUR, which highlighting its pharmacological potential in the treatment of drug-induced liver injury.