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1.
Food Chem ; 399: 133867, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35994856

RESUMO

This study aimed to investigate changes of fat globules and their membranes, and further analyze evolution of lipid profile of lipid rafts in membranes during heat processing of cow milk. Size of fat globules increased from 3.16 µm to 3.70 µm and ζ-potential decreased from -0.53 mV to -0.38 mV after thermal treatment, suggesting that fat globule membrane was destroyed and fat globule occurred coalescence. Glycerophospholipids and cholesterol in fat globule membrane decreased while sphingomyelin increased after thermal treatment. Results of lipidomics show that total of 38 species of 5 lipids molecule showed ability to differentiate the samples. At high temperatures, highly unsaturated glycerophospholipids and sterol lipids were lost from rafts, meanwhile, sphingomyelin and ceramide increased in this region. Significant change of lipid profile in the raft region during thermal treatment suggested a potential relationship between lipid rafts and fat globule coalescence behavior.


Assuntos
Glicolipídeos , Esfingomielinas , Animais , Bovinos , Feminino , Glicerofosfolipídeos , Glicoproteínas , Gotículas Lipídicas , Microdomínios da Membrana
2.
Bioact Mater ; 20: 208-220, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35702606

RESUMO

The process of bone repair is highly regulated by a large number of bioactive factors. Thus, a "cocktail" of bioactive factors supplemented to the defect sites is desirable for bone repair. In this regard, small extracellular vesicles (sEVs) derived from mesenchymal stem cells hold great potential in tissue repair. Nevertheless, the poor homing and retention of sEVs greatly limited their possible clinical application. In the present work, DMPE-PEG-CREKA was inserted into the membrane of sEVs released from adipose-derived mesenchymal stem cells to obtain CREKA functionalized sEVs (CREKA-sEVs), which could target fibrin to accumulate and retain in bone defects. Our results showed that CREKA-sEVs, like sEVs, promoted the osteogenic differentiation of BMSCs, the angiogenic property of HUVECs, and modulated the polarization of macrophages in vitro. Furthermore, due to the improved fibrin-binding and retention capacity of CREKA-sEVs, they enhanced the bone repair substantially in the rat femoral defect model. This study provided a new strategy to improve the therapeutic efficiency of sEVs and showed that CREKA-sEVs had great application value in bone tissue repair.

3.
Front Neurol ; 13: 860290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493835

RESUMO

Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) were used to detect the neuroimaging mechanism of Shugan Jieyu Capsule (SG) in ameliorating depression of post-stroke depression (PSD) patients. Fifteen PSD patients took SG for 8 weeks, completed the 24-item Hamilton Depression Scale (HAMD) assessment at the baseline and 8 weeks later, and underwent functional magnetic resonance imaging (fMRI) scanning. Twenty-one healthy controls (HCs) underwent these assessments at the baseline. We found that SG improved depression of PSD patients, in which ReHo values decreased in the left calcarine sulcus (CAL.L) and increased in the left superior frontal gyrus (SFG.L) of PSD patients at the baseline. The fALFF values of the left inferior parietal cortex (IPL.L) decreased in PSD patients at the baseline. Abnormal functional activities in the brain regions were reversed to normal levels after the administration of SG for 8 weeks. Receiver operating characteristic (ROC) analysis found that the changes in three altered brain regions could be used to differentiate PSD patients at the baseline and HCs. Average signal values of altered regions were related to depression in all subjects at the baseline. Our results suggest that SG may ameliorate depression of PSD patients by affecting brain region activity and local synchronization.

4.
Adipocyte ; 11(1): 562-571, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36053001

RESUMO

Mitochondrial dysfunction is associated with insulin resistance and type 2 diabetes (T2DM). Decreased mitochondrial abundance and function were found in white adipose tissue (WAT) of T2DM patients. Therefore, promoting WAT mitochondrial biogenesis and improving adipocyte metabolism may be strategies to prevent and reverse T2DM. Salvianolic acid A (SAA) has been found to exert anti-diabetic and lipid disorder-improving effects. However whether SAA benefits mitochondrial biogenesis and function in adipose tissue is unclear. Here, we evaluated SAA's effect on mitochondrial biogenesis and function in 3T3-L1 adipocytes and investigated its potential regulatory mechanism. Results showed that SAA treatment significantly promoted the transcription and expression of peroxisome proliferator-activated receptor γ coactivator- 1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM). Meanwhile, SAA treatment significantly promoted mitochondrial biogenesis by increasing mitochondrial DNA (mtDNA) quantity, mitochondrial mass, and expression of mitochondrial respiratory chain enzyme complexes III and complex IV. These enhancements were accompanied by enhanced phosphorylation of AMPK and ACC and were suppressed by Compound C, a specific AMPK inhibitor. Furthermore, SAA treatment improved adipocytes mitochondrial respiration and stimulated ATP generation. These findings indicate that SAA exerts a potential therapeutic capacity against adipocytes mitochondrial dysfunction in diabetes by activating the AMPK-PGC-1α pathway.


Assuntos
Diabetes Mellitus Tipo 2 , Biogênese de Organelas , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Animais , Ácidos Cafeicos , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , DNA Mitocondrial/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Lactatos , Camundongos , Mitocôndrias/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
6.
Appl Bionics Biomech ; 2022: 1497847, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36071814

RESUMO

Objective: To analyze the application of standardized nursing procedures in critically ill patients' nursing evaluation. Methods: 90 cases of critically ill patients aged from 18 to 65 who were treated in our hospital from April 2020 to April 2021 were selected and divided into the control group and observation group, respectively, with 45 cases according to the drawing method. The rescue time, blood pressure, heart rate before and after nursing, adverse mood, length of stay, incidence of adverse events, ICU transfer and death, and satisfaction of 2 groups were statistically analyzed and compared. Results: The rescue time of cardiopulmonary resuscitation, oxygen inhalation, venous opening, and endotracheal resuscitation in the observation group was 3.24 ± 1.01, which is lower than that in the control group, 6.65 ± 2.11, with statistical significance (P < 0.05). Similarly, the vital signs in the observation group were 2.45 ± 0.44, which is also significantly lower than that in the control group, 5.67 ± 1.56. After nursing, the blood pressure and heart rate in the observation group were lower than those in control group, with statistical significance (P < 0.05). The adverse mood of the observation group after nursing was lower than that of the control group, with statistical significance (P < 0.05). The length of stay, incidence of adverse events, intensive care unit (ICU) transfer, and death in the observation group were lower than those in the control group, with statistical significance (P < 0.05). The length of stay in the observation group was 8.87 ± 2.11, while 11.34 ± 2.45 in the observation group. The incidence of adverse events in the observation group was 1, while 8 in the observation group. The length of stay in the observation group was 8.87 ± 2.11, while 11.34 ± 2.45 in the observation group. The ICU transfer in the observation group were 2, while 9 in the observation group. There was no death in the observation group, however, 4 in the observation group. Nursing satisfaction in the observation group was higher than that in the control group, with statistical significance (P < 0.05). The number of patients that are very satisfied in the observation group was 28, while 20 in the control group. The number of patients that are satisfied in the observation group was the same as in the control group, both 15. However, the number of patients that are dissatisfied in the observation group was 2, while 10 in the control group. Conclusion: The application of the standardized nursing process in the nursing of critically ill patients can not only effectively reduce the self-rating anxiety scale (SAS) and sarcoidosis diagnostic score (SDS) of patients but also reduce the incidence of complications and improve the nursing satisfaction of patients.

7.
Front Cell Infect Microbiol ; 12: 983119, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046744

RESUMO

The larval stage of the tapeworm Echinococcus granulosus sensu lato (E. granulosus s.l.) caused a chronic infection, known as cystic echinococcosis (CE), which is a worldwide public health problem. The human secondary CE is caused by the dissemination of protoscoleces (PSCs) when fertile cysts are accidentally ruptured, followed by development of PSCs into new metacestodes. The local immune mechanisms responsible for the establishment and established phases after infection with E. granulosus s.l. are not clear. Here, we showed that T cells were involved in the formation of the immune environment in the liver in CE patients and Echinococcus granulosus sensu strict (E. granulosus s.s.)-infected mice, with CD4+ T cells being the dominant immune cells; this process was closely associated with cyst viability and establishment. Local T2-type responses in the liver were permissive for early infection establishment by E. granulosus s.s. between 4 and 6 weeks in the experimental model. CD4+ T-cell deficiency promoted PSC development into cysts in the liver in E. granulosus s.s.-infected mice. In addition, CD4+ T-cell-mediated cellular immune responses and IL-10-producing CD8+ T cells play a critical role in the establishment phase of secondary E. granulosus s.s. PSC infection. These data contribute to the understanding of local immune responses to CE and the design of new therapies by restoring effective immune responses and blocking evasion mechanisms during the establishment phase of infection.


Assuntos
Cistos , Equinococose , Echinococcus granulosus , Animais , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Modelos Animais de Doenças , Humanos , Imunidade Celular , Fígado , Camundongos
8.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4418-4427, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046871

RESUMO

Cold-heat combination is a common method in the treatment of ulcerative colitis, which is represented by classic drug pair, Coptidis Rhizoma and Zingiberis Rhizoma.The present study explored the synergetic effects of berberine and 6-shogaol, the primary components of Coptidis Rhizoma and Zingiberis Rhizoma, respectively, on intestinal inflammation and intestinal flora in mice with ulcerative colitis to reveal the effect and mechanism of cold-heat combination in the treatment of ulcerative colitis.The ulcerative colitis model was induced by dextran sulfate sodium(DSS) in mice.The model mice were administered with berberine(100 mg·kg~(-1)), 6-shogaol(100 mg·kg~(-1)), and berberine(50 mg·kg~(-1)) combined 6-shogaol(50 mg·kg~(-1)) by gavage, once per day.After 20 days of drug administration, mouse serum, colon tissues, and feces were sampled.Hematoxylin-eosin(HE) staining was used to observe histopathological changes in colon tissues.Alcian blue/periodic acid-Schiff(AB/PAS) staining was used to observe the changes in the mucus layer of colon tissues.Enzyme-linked immunosorbent assay(ELISA) was employed to detect the serum content of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6).Immunohistochemical method was adopted to detect the protein expression of macrophage surface markers F4/80, mucin-2, claudin-1, and zonula occludens-1(ZO-1) in colon tissues.High-throughput Meta-amplicon library sequencing was used to detect changes in the intestinal flora of mice.The results indicated that the 6-shogaol group, the berberine group, and the combination group showed significantly relieved intestinal injury, reduced number of F4/80-labeled positive macrophages in colon tissues, increased protein expression of mucin-2, claudin-1, and ZO-1, and decreased serum le-vels of TNF-α, IL-1ß, and IL-6.Shannon, Simpson, Chao, and Ace indexes of the intestinal flora of mice in the 6-shogaol group and the combination group significantly increased, and Chao and Ace indexes in the berberine group significantly increased.As revealed by the bioinformatics analysis of intestinal flora sequencing, the relative abundance of Verrucomicrobia at the phylum, class, and order levels decreased significantly in all treatment groups after drug administration, while that of Bacillibacteria gradually increased.In the 6-shogaol group and the combination group, Akkermansia muciniphila completely disappeared, but acid-producing bacillus still existed in large quantities.As concluded, both 6-shogaol and berberine can inhibit intestinal inflammation, reduce the infiltration and activation of macrophages, relieve intestinal damage, reduce intestinal permeability, improve the structure of flora, and promote intestinal microecological balance.The combined application of berberine and 6-shogaol has a significant synergistic effect.


Assuntos
Berberina , Colite Ulcerativa , Colite , Medicamentos de Ervas Chinesas , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Catecóis , Claudina-1/metabolismo , Claudina-1/farmacologia , Claudina-1/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Colo , Sulfato de Dextrana/efeitos adversos , Sulfato de Dextrana/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mucina-2/metabolismo , Mucina-2/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
9.
World J Gastrointest Oncol ; 14(7): 1227-1238, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-36051095

RESUMO

Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade, malignant neoplasms that are mostly seen in young women in the second and third decades of life and are quite uncommon in children. Standard resection for benign and borderline neoplasms of the pancreas is associated with a substantial risk of postoperative morbidity and long-term functional impairment, whereas enucleation leads to less morbidity and preserves healthy parenchyma as well as exocrine and endocrine function. Enucleation of SPNs has been increasingly reported to be feasible and safe for preserving the normal physiological function of the pancreas, especially in teenagers and children. This review summarizes findings published in recent years on the enucleation of SPNs as well as potential future developments and directions. Enucleation has undoubtedly come to stay as an alternative surgical procedure for SPNs. However, many questions remain unresolved, and future directions toward the best surgical indication, the prevention and intervention of complications, especially pancreatic fistula, intraoperative resection margin safety assessment, and long-term oncology prognosis remain to be evaluated and should be explored in future clinical trials.

10.
Front Oncol ; 12: 985284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052262

RESUMO

Background: Biomarkers that predict the efficacy of first-line tyrosine kinase inhibitors (TKIs) are pivotal in epidermal growth factor receptor (EGFR) mutant advanced lung adenocarcinoma. Imaging-based biomarkers have attracted much attention in anticancer therapy. This study aims to use the machine learning method to distinguish EGFR mutation status and further explores the predictive role of EGFR mutation-related radiomics features in response to first-line TKIs. Methods: We retrospectively analyzed pretreatment CT images and clinical information from a cohort of lung adenocarcinomas. We entered the top-ranked features into a support vector machine (SVM) classifier to establish a radiomics signature that predicted EGFR mutation status. Furthermore, we identified the best response-related features based on EGFR mutant-related features in first-line TKI therapy patients. Then we test and validate the predictive effect of the best response-related features for progression-free survival (PFS). Results: Six hundred ninety-two patients were enrolled in building radiomics signatures. The 13 top-ranked features were input into an SVM classifier to establish the radiomics signature of the training cohort (n = 514), and the predictive score of the radiomics signature was assessed on an independent validation group with 178 patients and obtained an area under the curve (AUC) of 74.13%, an F1 score of 68.29%, a specificity of 79.55%, an accuracy of 70.79%, and a sensitivity of 62.22%. More importantly, the skewness-Low (≤0.882) or 10th percentile-Low group (≤21.132) had a superior partial response (PR) rate than the skewness-High or 10th percentile-High group (p < 0.01). Higher skewness (hazard ratio (HR) = 1.722, p = 0.001) was also found to be significantly associated with worse PFS. Conclusions: The radiomics signature can be used to predict EGFR mutation status. Skewness may contribute to the stratification of disease progression in lung cancer patients treated with first-line TKIs.

11.
Arthritis Rheumatol ; 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36054683

RESUMO

OBJECTIVE: Mounting evidences have linked microbiome and metabolome to systemic autoimmunity and cardiovascular diseases (CVDs). A rare disease sharing features of immune-related inflammatory diseases and CVDs, Takayasu arteritis (TA), has limited relative information. This study aimed to characterize gut microbial dysbiosis, and its crosstalk with phenotypes in TA. METHODS: To address the discriminatory signatures, we performed shotgun sequencing of fecal metagenome across discovery cohort (n=97) and independent validation cohort (n=75) encompassing TA patients, healthy and Bechet's disease (BD) controls. Interrogation of untargeted metabolomics and lipidomics profiling of plasma and fecal samples was also employed to refine features mediating associations between microorganisms and TA phenotypes. RESULTS: A combined model of bacterial species encompassing unclassified Escherichia, Veillonella parvula, Streptococcus parasanguinis, Dorea formicigenerans, Bifidobacterium adolescentis, Lachnospiraceae bacterium 7 1 58FAA, Escherichia coli, Streptococcus salivarius, Klebsiella pneumoniae, Bifidobacterium longum and Lachnospiraceae Bacterium 5 1 63FAA, discriminated TA from controls with area under curves (AUCs) of 87.8%, 85.9%, 81.1%, and 71.1% in training, test, validation sets including healthy or BD controls, respectively. Diagnostic species were directly or indirectly via metabolites or lipids correlated with TA phenotypes of vascular involvement, inflammation, discharge medication, and prognosis. External validation against publicly metagenomic studies (n=184) on hypertension, atrial fibrillation and healthy controls, confirmed the TA-diagnostic accuracy of the model. CONCLUSION: This study firstly identifies the discriminatory gut microbes in TA. Dysbiotic microbes also link to TA phenotypes directly or indirectly via metabolic and lipid modules. Further explorations on microbiome-metagenome interface in TA subtype prediction and pathogenesis are indicated.

12.
Open Life Sci ; 17(1): 881-892, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36045718

RESUMO

Early-stage non-small cell lung cancer (NSCLC) patients are at substantial risk of poor prognosis. We attempted to develop a reliable metabolic gene-set-based signature that can predict prognosis accurately for early-stage patients. Least absolute shrinkage and selection operator method Cox regression models were performed to filter the most useful prognostic genes, and a metabolic gene-set-based signature was constructed. Forty-two metabolism-related genes were finally identified, and with specific risk score formula, patients were classified into high-risk and low-risk groups. Overall survival was significantly different between the two groups in discovery (HR: 5.050, 95% CI: 3.368-7.574, P < 0.001), internal validation series (HR: 6.044, 95% CI: 3.918-9.322, P < 0.001), GSE30219 (HR: 2.059, 95% CI: 1.510-2.808, P < 0.001), and GSE68456 (HR: 2.448, 95% CI: 1.723-3.477, P < 0.001). Survival receiver operating characteristic curve at the 5 years suggested that the metabolic signature (area under the curve [AUC] = 0.805) had better prognostic accuracy than any other clinicopathological factors. Further analysis revealed the distinct differences in immune cell infiltration and tumor purity reflected by an immune and stromal score between high- and low-risk patients. In conclusion, the novel metabolic signature developed in our study shows robust prognostic accuracy in predicting prognosis for early-stage NSCLC patients and may function as a reliable marker for guiding more effective immunotherapy strategies.

13.
J Inflamm Res ; 15: 4817-4831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046661

RESUMO

Purpose: To conduct the first whole exome sequencing (WES) on Takayasu arteritis (TAK) to identify common and rare variants responsible for disease susceptibility. Patients and Methods: A total of 200 patients and 1675 healthy controls from China were recruited for this study. Site-based association analysis for common variants and gene-based burden analysis for rare variants were conducted. A weighted genetic risk score (wGRS) was calculated for each patient with TAK based on the independent risk alleles identified in the association analyses. The ability of the patient wGRS to discriminate between different phenotypes was evaluated. Results: In the site-based analysis, the top association signal was CCHCR1 (rs1265067, p = 8.27 × 10-12, OR = 2.41), a proxy for HLA-B*52:01. HLA-DQB1 (rs9273902), HLA-DQB2 (rs34109750), and a haplotype block in the human leukocyte antigen (HLA) class III region (represented by rs3130618) also exhibited significant associations independently. In addition, four novel non-HLA susceptibility loci were identified: PRRT4, TLL2, LRP1B, and DLGAP2. Twelve independently associated single nucleotide polymorphisms were used to calculate the wGRS. TAK patients with a higher wGRS were found to have an increased risk of pulmonary artery involvement compared with those with a lower wGRS (p = 5.76 × 10-7, OR = 13.92). The wGRS algorithm showed good predictive capability for pulmonary artery involvement in TAK (sensitivity, 92.1%; specificity, 59.9%). In the gene-based analysis, risk genes that reached exome-wide significance were not identified. Conclusion: This WES study on TAK supports a previously reported association within the HLA region. Moreover, novel susceptibility loci were identified outside the HLA region. These risk alleles showed potential associations with pulmonary artery involvement in TAK. However, additional studies are warranted to verify our findings.

14.
Front Chem ; 10: 973666, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046731

RESUMO

Cancer has emerged as one of the most severe diseases in modern times, various therapies have advanced remarkably in recent decades. Unlike the direct therapeutic targeting tumor cells, immunotherapy is a promising strategy that stimulate the immune system. In cancer immunotherapy, polymeric-based nanoparticles can serve as deliver systems for antigens and immunostimulatory molecules, and they have attracted increasing attention and revolutionized cancer therapy. Poly (lactic-co-glycolic acid) (PLGA) is the most frequently used clinically approved biodegradable polymer and has a broad scope of modification of its inherent properties. Recent advances in PLGA based drug delivery systems in cancer immunotherapy have been described in this mini review, with special emphasis on cancer vaccines and tumor microenvironment modulation.

15.
Kaohsiung J Med Sci ; 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36054229

RESUMO

Preeclampsia (PE) is a multisystemic and placental inflammatory disease that causes maternal and infant health issues. As one of the active components in peony root extract, paeonol (Pae) exerts anti-apoptosis and anti-inflammatory effects. Nonetheless, the protective role of Pae in PE has not yet been characterized. A mouse model of PE was constructed through tail vein injection of 1 mg/d phosphatidylserine/dioleoyl-phosphatidycholine suspension. The levels of inflammatory cytokines in the placenta were examined via enzyme-linked immunosorbent assay (ELISA). The mRNA levels of inflammatory cytokines (TNF-α, IL-6, IFN-γ, and IL-4) and apoptosis markers (Bax, Bcl-2, and caspase-3) were tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot analysis was performed to detect the protein levels of apoptosis markers and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules. Here, Pae repressed the inflammatory response in the placenta of PE-like mouse models, as demonstrated by the decreased concentrations and mRNA levels of TNF-α, IL-6, and IFN-γ and the increased concentrations and mRNA levels of IL-4. Apoptosis in the placentas of PE-like mouse models was attenuated by Pae, as manifested by the downregulated mRNA and protein levels of Bax and cleaved-caspase-3 and the upregulated Bcl-2. Administration of Pae inhibited the phosphorylation of JAK2 and STAT3 in the placental tissues of PE mice. The JAK2/STAT3 pathway agonist (SC-39100) reversed Pae treatment-mediated suppression of placental inflammation and apoptosis in PE mice. Overall, Pae inhibits the JAK2/STAT3 signaling pathway to attenuate placental inflammation and apoptosis in PE mice.

16.
Clin Exp Rheumatol ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36062744

RESUMO

OBJECTIVES: Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of antiphospholipid syndrome (APS) with high mortality. We try to develop a predictive model to achieve early recognition of CAPS. METHODS: Data of APS patients referred into Peking Union Medical College Hospital from May 2013 to October 2021 was collected. A binary logistic regression method was used to identify predictors of CAPS, coefficient B was assigned with score value in the development of prediction model, and risk-stratification was based on the calculated scores using the model. RESULTS: Twenty-seven CAPS (11.9%) occurred in 226 APS patients. CAPS was more likely to occur in male secondary APS patients with a history of hypertension, hyperlipidaemia, and arterial thrombosis, presented with haematological, nephrological and immunological abnormalities simultaneously. Hypertension history (OR 5.091, 95% CI 1.119-23.147), anaemia (OR 116.231, 95% CI 10.512-1285.142), elevated LDH (OR 59.743, 95% CI 7.439-479.815) and proteinuria (OR 11.265, 95% CI 2.118-59.930) were independent predictors for CAPS, and the scores were 1, 3, 3 and 2 points, respectively. The risk scores were divided into high-risk (6-9) and low risk (0-5), the risk for CAPS were 54.1% and 0.6%, with sensitivity of 0.963 and specificity of 0.886. The Nagelkerke's R2 (0.739) and the Omnibus test (χ2 =109.231, df=4, p=0.000) indicated the model has a good fit. The AUC of 0.971 indicated good discrimination. The calibration curve in internal validation showed good calibration of this predictive model. CONCLUSIONS: A predictive model of CAPS was developed with hypertension, anaemia, elevated LDH and proteinuria. This model could help identify CAPS in high-risk patients, achieve early recognition and intervention to improve prognosis.

17.
Protein Pept Lett ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045540

RESUMO

Platycodon grandiflorus is a well-known and widely distributed traditional herbal medicine and functional food in Asia, with triterpenoids as the main bioactive component in its roots. Acetyl-CoA C-acetyltransferase (AACT) is the initiation enzyme in the mevalonate pathway and plays an important role in the biosynthesis of terpenoids. OBJECTIVE: The objective of this study was to clone and identify PgAACT function in P. grandiflorus. METHOD: The full-length sequence of PgAACT genes was isolated and cloned from P. grandiflorus by polymerase chain reaction (PCR). The recombinant plasmid was constructed using the pET-32a vector and expressed in E. coli Transetta (DE3) cells. Subcellular localization of AACT was observed in the epidermal cells of N. tabacum. Quantitative reverse transcription-PCR(qRT-PCR) was used to identify the PgAACT gene transcription levels. After MeJA treatment, the changes of AACT genes expression were observed, UHPLC-Q-Exactive Orbitrap MS/MS was used to detect the changes of P. grandiflorus saponins. RESULTS: In this study, two full-length cDNAs encoding AACT1 (PgAACT1) and AACT2 (PgAACT2) were isolated and cloned from P. grandiflorus. The deduced PgAACT1 and PgAACT2 proteins contain 408 and 416 amino acids, respectively. The recombinant vectors were constructed, and the protein expression was improved by optimizing the reaction conditions. Sodium dodecyl sulphate-polycrylamide gel electrophloresis and western blot analysis showed that the PgAACT genes were successfully expressed, with molecular weights of the recombinant proteins of 61 and 63 kDa, respectively. Subcellular localization showed that the PgAACT genes were localized in the cytoplasm. Tissue specificity analysis of P. grandiflorus from different habitats showed that PgAACT genes were expressed in the roots, stems, and leaves. After MeJA treatment, the expression level of PgAACT genes and the content of total saponins of P. grandiflorus were significantly increased, suggesting that PgAACT genes play an important role in regulating plant defense systems. CONCLUSION: Cloning, expression, and functional analysis of PgAACT1 and PgAACT2 will be helpful in understanding the role of these two genes in terpene biosynthesis.

18.
Adv Sci (Weinh) ; : e2202620, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047655

RESUMO

Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio-synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene-related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity-modifying protein 1 (RAMP1) and cyclic AMP response element-binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

19.
Expert Rev Vaccines ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048417

RESUMO

BACKGROUND: The demonstration of batch-to-batch consistency is indispensable for quality control of vaccines. METHODS: We did a randomized, double-blind, parallel-controlled trial to evaluate the immunogenicity consistency of one shot of Ad5-nCoV in healthy adults who had not received any COVID-19 vaccine before. All eligible participants were randomly assigned equally to receive one of three consecutive batches of Ad5-nCoV (5×1010 viral particles/vial, 0.5 mL). The primary endpoint was geometric mean titers (GMTs) of serum SARS-CoV-2 receptor binding domain (RBD)-specific IgG on day 28 post-vaccination. RESULTS: 1050 participants were enrolled, with 350 (33%) participants per group. On day 28 post-vaccination, GMTs in three groups were 78.3 binding antibody units (BAU)/mL (95% CI 70.3-87.3), 82.9 BAU/mL (73.9-92.9) and 78.8 BAU/mL (70.2-88.4), respectively. The two-sided 95% CIs for the GMT ratios between each pair of batches were all between 0.67 and 1.5. The highest incidence of solicited adverse reactions within 7 days post-vaccination was reported by batch 3 recipients (23.1% versus 15.1% in batch 1 recipients and 14.6% in bath 2 recipients; p=0.0039). None of serious adverse events were related to the vaccination. CONCLUSIONS: The immunogenicity consistency between consecutive batches of Ad5-nCoV was well established in adults.This trial was registered with ClinicalTrials.gov (NCT05313646).

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(9): 781-788, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36082707

RESUMO

Objective To compare the expression level of P-selectin (CD62P) on platelets surface under the stimulation of Staphylococcus aureus (SA) and Escherichia coli (E.coli), explore the inhibitory effects of platelets on the their proliferation, and further investigate the molecular mechanism by which platelets inhibit the proliferation of bacteria. Methods 106 CFU/mL SA and E.coli were co-cultured with 2×1011/L purified platelets, and the A600 values of the two groups were detected; The CD62P of platelets was detected by flow cytometry after platelets co-cultured with SA and E.coli for 2 hours and 4 hours. The platelet factor 4 (PF4) released by platelets was detected by ELISA; After co-cultured with SA and E.coli for 12 hours, the proliferation, phosphatidylserine (PS) eversion and cell membrane potential of SA and E.coli were analyzed by flow cytometry. Results After platelets co-cultured with SA and E.coli for 6 hours, the turbidity of SA decreased significantly and the turbidity of E.coli showed a slight decrease. Compared with the control group, the counts of bacterial plates decreased after two kinds of bacteria co-cultured with platelets. After co-cultured with SA and E.coli for 2 hours and 4 hours, the CD62P levels of platelets increased. In particular, the CD62P level of platelets co-cultured with SA was significantly higher than that of platelets co-cultured with E.coli. The release of intracellular protein PF4 of platelet increased significantly after bacteria stimulation. The proliferation rate of SA and E.coli decreased after co-cultured with platelets, and SA and E.coli exhibited PS eversion and depolarization of cell membrane potential. Conclusion High expression of CD62P inhibits the proliferation and induces apoptotic changes of SA and E.coli after platelets activation in vitro, and the inhibitory effect of platelets on SA was better than that of E.coli.


Assuntos
Selectina-P , Ativação Plaquetária , Apoptose , Plaquetas , Proliferação de Células , Escherichia coli/metabolismo , Citometria de Fluxo , Selectina-P/metabolismo
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