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1.
Food Chem ; 399: 133926, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36007446

RESUMO

Pigmented rice, particularly black rice, has attracted widespread global interest due to its high nutritional value. To obtain a better understanding of differential metabolites between pigmented rice and white rice, we used a widely-targeted metabolomics-based approach to investigate the metabolite profiling of black, red, glutinous, and common white rice. In total, 732 metabolites were identified, of which 281, 305, 241, 267, and 265 differential metabolites were screened by comparing the following group: glutinous/white vs black, glutinous/white vs red, and red vs black. Venn diagram demonstrated that 69 metabolites were shared between pigmented and non-pigmented rice, and 117 between glutinous/white/red vs black. Additionally, metabolic pathways analysis of differential metabolites in glutinous/white/red vs black revealed that the flavonoid biosynthesis, anthocyanin biosynthesis, and flavone and flavonol biosynthesis are differential enrichment metabolic pathways. As such, identifying these different metabolites contribute to a better understanding of the function and nutritional value of various rice strains.


Assuntos
Oryza , Redes e Vias Metabólicas , Metabolômica , Oryza/genética , Oryza/metabolismo
2.
Toxicology ; 483: 153386, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36460222

RESUMO

Infertility gives rise to a lot of social and psychological problems. At present, assisted reproductive technology (ART) is an important way to solve infertility. However, the live birth rate of in vitro fertilization and embryo transfer (IVF-ET) is less than 50 %. Medium is essential for the culture of embryos in vitro. Therefore, we want to explore whether the composition of the culture medium affects the survival rate of embryos. Gentamicin (GM) is an aminoglycoside antibiotic that is used to treat various bacterial infections. It is widely used in IVF medium, but it is not known whether it has a toxicity effect on embryonic development. Here, we used zebrafish embryos to investigate the embryotoxicity of GM which is an ingredient in culture medium. Our results found that there was no significant effect on the zebrafish embryo development, including survival rate, malformation rate and developmental time course, while zebrafish embryos were treated with GM at the culture medium concentration (10 mg/L, 17.8 µM) compared with the control group. To research the potential embryotoxicity of GM, we treated zebrafish embryos with GM with high concentration (range from 17.8 µM to 3000 µM). The results showed that the lethal concentration of 50 % (LC50) at 48-h post-fertilization (hpf) value of zebrafish embryos for GM was 1150 µM; the survival rate and malformation rate of zebrafish embryos were significantly changed in a dose-dependent manner. Furthermore, transcriptomics, metabolomics and epigenomics (m6A-MeRIP-seq) were used to investigate the molecular mechanism of embryotoxicity, and results showed cell cycle, dorso-ventral axis formation and collecting duct acid secretion pathway were altered significantly in treated embryos. In conclusion, there are no adverse effects on embryonic development with the working concentration of GM in human culture medium, suggesting that GM is safe for embryo culture at working concentration.

3.
Environ Int ; 171: 107654, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36462434

RESUMO

BACKGROUND: Residential greenness has been linked to respiratory mortality, but its long-term effect on incident chronic obstructive pulmonary disease (COPD) has rarely been investigated. METHODS: This prospective cohort study was based on over 350 000 participants aged 38-70 of the UK Biobank, followed from 2006 to 2010 baseline to 2021. COPD cases were ascertained through linkages to health administrative datasets. Residential greenness was measured by satellite-derived normalized difference vegetation index (NDVI) within the 500- and 1 000-m buffer. Effects of greenness on COPD incidence were assessed using Cox proportional hazards models. We also explored mediation by physical activity, particular matter <2.5 µm in aerodynamic diameter (PM2.5) and nitrogen oxides (NOx). Restricted cubic spline models were fit to assess exposure-response relationships. RESULTS: A total of 363 212 individuals (mean [SD] age, 56.2 [8.1] years; 193 181 [53.2 %] women] were included in the analyses. 8 261 COPD cases occurred over 4 287 926 person-years of follow-up. We observed 8% lower COPD risk per IQR increase in NDVI in the 500-m buffer (95% CI: 0.89, 0.95). The association between greenness in the 500-m buffer and COPD were partially mediated by physical activity (1.0%, 95% CI: 0.2%, 1.8%), PM2.5 (21.0%, 95% CI: 3.7%, 38.4%) and NOx (17.0%, 95% CI: 2.8%, 31.2%). Similar results were observed for NDVI within 1 000-m buffer. CONCLUSIONS: Long-term exposure to residential greenness was associated with lower risk of COPD incidence among UK adults. Our findings provide a rationale for greening policies as part of respiratory health promotion efforts.

4.
Food Res Int ; 162(Pt B): 112097, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461403

RESUMO

Milk fat globule membrane (MFGM) proteins, which are recognized to play a variety of biological roles; nevertheless, their composition and interspecies complexity remain unknown. This study aimed to identify and quantify proteins extracted from MFGM-enriched fractions of bovine, goat and camel milk by a label free proteomics approach. We identified 1579 proteins, substantially increasing the number of MFGM proteins identified for these species. The results of functional analysis showed that the identified MFGM proteins had similar functional annotations, with cellular processes, intracellular anatomical structures and binding being the predominant GO annotations. And most of the proteins were involved in KEGG pathways such as protein processing of ribosomes and endoplasmic reticulum. Subsequently, multiple statistical methods were used to compare the differences in MFGM protein quantification among different species. The results of principal component analysis showed that bovine, goat and camel milk MFGM proteins were significantly different, among which CSN1S1, XDH, LTF and PI4KA played an important role in taxonomic identification. Meanwhile the results of hierarchical clustering showed that the differences (p < 0.05) between bovine and goat milk were smaller than those of camel milk. These new data deepen the understanding of the protein composition of MFGM and its possible physiological roles, providing directions for the production of specific functional milk proteins.

5.
Front Endocrinol (Lausanne) ; 13: 962154, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36465612

RESUMO

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats.

6.
Front Vet Sci ; 9: 1008107, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36467650

RESUMO

Bovine viral diarrhea virus (BVDV) is an important livestock viral pathogen responsible for causing significant economic losses. The emerging and novel BVDV isolates are clinically and biologically important, as there are highly antigenic diverse and pathogenic differences among BVDV genotypes. However, no study has yet compared the virulence of predominant genotype isolates (BVDV-1a, 1b, and 1m) in China and the emerging genotype isolate BVDV-1v. The serological relationship among these genotypes has not yet been described. In this study, we isolated three BVDV isolates from calves with severe diarrhea, characterized as BVDV-1a, 1m, and novel 1v, based on multiple genomic regions [including 5-untranslated region (5'-UTR), Npro, and E2] and the phylogenetic analysis of nearly complete genomes. For the novel genotype, genetic variation analysis of the E2 protein of the BVDV-1v HB-03 strain indicates multiple amino acid mutation sites, including potential host cell-binding sites and neutralizing epitopes. Recombination analysis of the BVDV-1v HB-03 strain hinted at the possible occurrence of cross-genotypes (among 1m, 1o, and 1q) and cross-geographical region transmission events. To compare the pathogenic characters and virulence among these BVDV-1 genotypes, newborn calves uninfected with common pathogens were infected intranasally with BVDV isolates. The calves infected with the three genotype isolates show different symptom severities (diarrhea, fever, slowing weight gain, virus shedding, leukopenia, viremia, and immune-related tissue damage). In addition, these infected calves also showed bovine respiratory disease complexes (BRDCs), such as nasal discharge, coughing, abnormal breathing, and lung damage. Based on assessing different parameters, BVDV-1m HB-01 is identified as a highly virulent strain, and BVDV-1a HN-03 and BVDV-1v HB-03 are both identified as moderately virulent strains. Furthermore, the cross-neutralization test demonstrated the antigenic diversity among these Chinese genotypes (1a, 1m, and 1v). Our findings illustrated the genetic evolution characteristics of the emerging genotype and the pathogenic mechanism and antigenic diversity of different genotype strains, These findings also provided an excellent vaccine candidate strain and a suitable BVDV challenge strain for the comprehensive prevention and control of BVDV.

7.
Comput Biol Med ; 151(Pt A): 106289, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36401973

RESUMO

As a non-coding RNA molecule with closed-loop structure, circular RNA (circRNA) is tissue-specific and cell-specific in expression pattern. It regulates disease development by modulating the expression of disease-related genes. Therefore, exploring the circRNA-disease relationship can reveal the molecular mechanism of disease pathogenesis. Biological experiments for detecting circRNA-disease associations are time-consuming and laborious. Constrained by the sparsity of known circRNA-disease associations, existing algorithms cannot obtain relatively complete structural information to represent features accurately. To this end, this paper proposes a new predictor, VGAERF, combining Variational Graph Auto-Encoder (VGAE) and Random Forest (RF). Firstly, circRNA homogeneous graph structure and disease homogeneous graph structure are constructed by Gaussian interaction profile (GIP) kernel similarity, semantic similarity, and known circRNA-disease associations. VGAEs with the same structure are employed to extract the higher-order features by the encoding and decoding of input graph structures. To further increase the completeness of the network structure information, the deep features acquired from the two VGAEs are summed, and then train the RF with sparse data processing capability to perform the prediction task. On the independent test set, the Area Under ROC Curve (AUC), accuracy, and Area Under PR Curve (AUPR) of the proposed method reach up to 0.9803, 0.9345, and 0.9894, respectively. On the same dataset, the AUC, accuracy, and AUPR of VGAERF are 2.09%, 5.93%, and 1.86% higher than the best-performing method (AEDNN). It is anticipated that VGAERF will provide significant information to decipher the molecular mechanisms of circRNA-disease associations, and promote the diagnosis of circRNA-related diseases.

8.
Complement Med Res ; 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36349756

RESUMO

INTRODUCTION: Postoperative gastrointestinal tract dysfunction is considered a common complication affecting patients undergoing intestinal surgery. This research aims to provide evidence to assess the efficacy and safety of Baizhu Shaoyao San (BSS) or modified BSS in treating postoperative diarrhea of colorectal cancer patients. METHODS: Eighty patients with colorectal cancer were randomized within two weeks after surgery to receive either modified BSS or Loperamide combined with the respective dummy. The curative effect was evaluated with the traditional Chinese medicine (TCM) syndrome score. Determination of motilin and gastrin in plasma was conducted utilizing ELISA. RESULTS: Compared with Loperamide therapy, the efficacy of modified BSS was statistically significant, the traditional Chinese medicine syndrome score decreased, and the total effective rate increased. Levels of motilin and gastrin in plasma decreased. CONCLUSION: The curative effect and safety of modified BSS were statistically significant.

9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(9): 927-930, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36377445

RESUMO

OBJECTIVE: To explore the impact of completion rates of 3-hour and 6-hour sepsis bundle therapy on prognosis of patients with septic shock in Prefecture-level grade A hospitals, and analyze the risk factors for prognosis. METHODS: A retrospective analysis was conducted to patients with septic shock in the intensive care unit (ICU) of Liaocheng People's Hospital, Shandong Province from January 1, 2020 to December 31, 2021. The data of gender, age, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), sites of infection, pathogenic microorganisms, completion rates of 3-hour and 6-hour sepsis bundle therapy, 28-day prognosis were collected. Logistic regression analysis was used to identify risk factors for patients' mortality at 28-day. RESULTS: (1) Among 159 patients with septic shock, 93 survived and 66 died with 28-day. There were no significant differences in gender and age between the survival group and death group. Compared with the survival group, APACHE II score and SOFA score were significantly higher in the death group [APACHE II score: 26.85±5.04 vs. 20.67±4.29, SOFA score: 12.86±3.02 vs. 9.37±2.51, both P < 0.05]. (2) Sites of infection in the 159 patients: 47 cases were abdominal infection (29.6%), 36 case were bloodstream infection (22.6%), 31 cases were pulmonary infection (19.5%), 16 cases were soft tissue infection (10.1%), 13 cases were urinary tract infection (8.2%), 12 cases were biliary tract infection (7.5%), and 4 cases were other sites infection (2.5%). Pathogens were found in 128 cases and the positive rate was 80.5%, including 90 cases of Gram-negative (G-) bacilli (56.6%), 27 cases of Gram-positive (G+) cocci (17.0%) and 11 cases of fungi (6.9%). The top three pathogenic bacteria were Escherichia coli (49 cases, 30.8%), Klebsiella pneumoniae (21 cases, 13.2%) and Staphylococcus aureus (15 cases, 9.4%). The differences were not statistically significant. (3) Among the 159 patients, 101 cases completed 3-hour sepsis bundle therapy (63.5%), including 67 cases (72.0%) in survival group and 34 cases (51.5%) in death group; 106 cases completed 6-hour sepsis bundle therapy (66.7%), including 70 cases (75.3%) in survival group and 36 cases (54.5%) in death group. The differences between the two groups were statistically significant (all P < 0.05). (4) The factors (APACHE II score, SOFA score and completion rate of 3-hour and 6-hour sepsis bundle therapy) affecting the prognosis in the univariate analysis were included in the binary Logistic regression analysis, and the results showed that the APACHE II score, SOFA score, completion rate of 3-hour sepsis bundle therapy were independent risk factors affecting mortality within 28-day [odds ratio (OR) was 1.216, 1.303, 0.402, all P < 0.05]. CONCLUSIONS: The higher APACHE II score and SOFA score in septic shock, the worse the prognosis. Improving the completion rates of 3-hour and 6-hour bundle therapy especially the completion rate of 3-hour bundle therapy can reduce the mortality of patients and improve the prognosis.


Assuntos
Infecções Intra-Abdominais , Sepse , Choque Séptico , Humanos , Choque Séptico/diagnóstico , Choque Séptico/terapia , Estudos Retrospectivos , Curva ROC , Prognóstico , Unidades de Terapia Intensiva
10.
Ann Med ; 54(1): 2951-2965, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36382675

RESUMO

BACKGROUND: Cytopenia is one of the most common adverse events following the CAR-T cell infusion, affecting the quality of life and potentially leading to life-threatening bleeding and infection. This study aimed to systematically review the cytopenias following anti-CD19 CAR-T therapy and further analyse the contributing factors. METHODS: Databases including PubMed, MEDLINE, Embase and Cochrane were systematically searched on 8 May 2022. A random-effect meta-analysis was used to estimate the incidence of cytopenia, and subgroup analyses were applied to explore heterogeneity. RESULTS: A total of 68 studies involving 2950 patients were included in this study. The overall incidence of all grade anaemia, thrombocytopenia, neutropenia, leukopoenia, lymphocytopenia and febrile neutropenia was 65%, 55%, 78%, 62%, 70% and 27%, respectively, and the corresponding cytopenias of grade 3 or worse were 33%, 31%, 61%, 45%, 46%, and 21%, respectively. Subgroup analysis showed increased incidence of cytopenias in subgroups with lower median age, proportion of males (<65%) and proportion of bridging therapy (<80%) and in the subgroup with a median line of prior therapy ≥3. In terms of disease and therapeutic target, cytopenias were more frequent in ALL patients and in dual-target CAR-T therapies (targeting CD19 in combination with other targets). Furthermore, CAR-T products manufactured by lentiviral vectors and those with the costimulatory domain of CD28 were more likely to cause haematological toxicity. No significant differences were observed in cytopenia between patients treated with CAR-T products with murine and humanized scFv. CONCLUSION: In conclusion, neutropenia is the most frequent cytopenia after CAR-T therapy, both in all grades or grade ≥3. The incidence of cytopenias following CAR-T therapy is influenced by the age, sex, disease and number of prior therapy lines of the patients, as well as the target and costimulatory domain of CAR-T cells, and viral vectors used for manufacturing.KEY MESSAGESNeutropenia is the most frequent cytopenia after CAR-T therapy.The clinical characteristics of the patients, the design of CAR-T cells and the protocol of CAR-T treatment can influence the occurrence of cytopenias following the CAR-T therapy.


Assuntos
Anemia , Neutropenia , Receptores de Antígenos Quiméricos , Trombocitopenia , Masculino , Humanos , Camundongos , Animais , Qualidade de Vida , Antígenos CD19/uso terapêutico , Trombocitopenia/epidemiologia , Trombocitopenia/etiologia , Trombocitopenia/terapia , Neutropenia/epidemiologia , Neutropenia/etiologia , Neutropenia/tratamento farmacológico , Terapia Baseada em Transplante de Células e Tecidos
11.
Artigo em Inglês | MEDLINE | ID: mdl-36420886

RESUMO

OBJECTIVE: To investigate the differences and their clinical significance in the intestinal microbiota in patients with Parkinson's disease (PD) in comparison to those in healthy controls. MATERIALS AND METHODS: 20 patients with PD who received treatment in the First Affiliated Hospital of Bengbu Medical College between January 2019 and December 2019 were selected as the research subjects to form the PD group, while 20 age- and gender-matched healthy volunteers were selected as the control group. Fecal samples from the two groups were collected, and the V4 region of 16S-ribosomal ribonucleic acid was selected for high-throughput sequencing analysis to explore any differences, as well as their significance, in the intestinal microbiota abundance at the class, family, and genus levels between the two study groups. RESULTS: The operational taxonomic unit cluster analysis revealed a high degree of overlap between the patients with PD and the controls. Compared with the controls, the relative abundance of Coriobacteriia and Coriobacteriaceae was increased in the PD group (p < 0.01), while the relative abundance of Lachnospiraceae was significantly lower (p < 0.01). The relative abundance of Collinsella, Escherichia, and Fusobacterium in the PD group was significantly higher than in the control group (p < 0.05). CONCLUSION: Compared with the healthy subjects, the abundance of specific microflora was significantly different in the PD patients at the class, family, and genus level. Intestinal flora may act as a potential biomarker for PD and provide a theoretical basis for microflora transplantation therapy.

12.
Eur Radiol ; 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435877

RESUMO

OBJECTIVES: To evaluate the potential diagnostic value of MR elastography (MRE)-based stiffness to noninvasively predict the microvascular invasion (MVI) grade in hepatocellular carcinoma (HCC). METHODS: One hundred eighty-five patients with histopathology-proven HCC who underwent MRI and MRE examinations before hepatectomy were retrospectively enrolled. According to the three-tiered MVI grading system, the MVI was divided into negative-MVI (n = 89) and positive-MVI (n = 96) groups, and the latter group was categorized into mild-MVI (n = 49) and severe-MVI (n = 47) subgroups. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were used to determine the predictors associated with MVI grade and analyze their performances, respectively. RESULTS: Among the 185 patients, tumor size ≥ 50 mm (p = 0.031), tumor stiffness (TS)/liver stiffness (LS) > 1.47 (p = 0.001), TS > 4.33 kPa (p < 0.001), and nonsmooth tumor margin (p = 0.006) were significant independent predictors for positive-MVI. Further analyzing the subgroups, tumor size ≥ 50 mm (p < 0.001), TS > 5.35 kPa (p = 0.001), and AFP level > 400 ng/mL (p = 0.044) were independently associated with severe-MVI. The models incorporating MRE and clinical-radiological features together performed better for evaluating positive-MVI (AUC: 0.846) and severe-MVI (AUC: 0.802) than the models using clinical-radiological predictors alone (AUC: positive-/severe-MVI, 0.737/0.743). Analysis of recurrence-free survival and overall survival showed the predicted positive-MVI/severe-MVI groups based on combined models had significantly poorer prognoses than predicted negative-MVI/mild-MVI groups, respectively (all p < 0.05). CONCLUSIONS: MRE-based stiffness was an independent predictor for both the positive-MVI and severe-MVI. The combination of MRE and clinical-radiological models might be a useful tool for evaluating HCC patients' prognoses underwent hepatectomy by preoperatively predicting the MVI grade. KEY POINTS: • The severe-microvascular invasion (MVI) grade had the highest tumor stiffness (TS), followed by mild-MVI and non-MVI, and there were significances among the three different MVI grades. • MR elastography (MRE)-based stiffness value was an independent predictor of positive-MVI and severe-MVI in hepatocellular carcinoma (HCC) preoperatively. • When combined with clinical-radiological models, MRE could significantly improve the predictive performance for MVI grade. Patients with predicted positive-MVI/severe-MVI based on the combined models had worse recurrence-free survival and overall survival than those with negative-MVI/mild-MVI, respectively.

13.
Int Ophthalmol ; 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411372

RESUMO

PURPOSE: To analyze the retinal ganglion cell-inner plexiform layer (GCIPL) changes in retinal vein occlusion (RVO) eyes with resolved macular edema using optical coherence tomography. METHODS: We compared the average and minimum GCIPL thickness in RVO eyes with fellow eyes and healthy controls including 40 unilateral RVO patients and 48 healthy subjects. The average GCIPL thickness in BRVO eyes was segmented into the affected and opposite area according to the site of lesion, comparing them with corresponding areas in fellow eyes. Furthermore, maximum central macular thickness (CMT), visual acuity (VA), and intravitreal injection times were recorded to investigate their relationship with the GCIPL thickness. RESULTS: Despite no significant difference in CMT (P = 0.96), the average (P = 0.02 and P < 0.001, respectively) and minimum (both P < 0.001) GCIPL thicknesses were decreased in RVO eyes with resolved macular edema after treatment in comparison to fellow eyes and healthy eyes. Maximum CMT thickness was negatively correlated with the minimum GCIPL thickness (r = - 0.47, P = 0.003). VA and average GCIPL thickness were associated (rs = - 0.49, P = 0.002). In a subgroup analysis that only included BRVO patients, the opposite area revealed no significant difference between two eyes (P = 0.91) although the affected area in BRVO eyes was decreased (P < 0.001). CONCLUSIONS: A decrease of GCIPL thickness in RVO was observed even after anatomic restoration and associated with VA prognosis. These GCIPL defects could be attributable to systemic risks and RVO itself, not anti-VEGF effects.

14.
Pediatr Nephrol ; 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36416954

RESUMO

Fibroblast growth factor 23 (FGF23) is primarily produced in bones and mainly regulates calcium and phosphorus metabolism. The level of circulating FGF23 increases rapidly in the early stage of acute kidney injury (AKI). Recent studies have shown that FGF23 may serve as a biomarker for the diagnosis and poor prognosis of AKI. The mechanism of increased FGF23 in AKI may include increased production of FGF23, decreased renal clearance of FGF23, and some new regulatory factors, such as inflammation and glycerol 3-phosphate. However, the biological effects of elevated FGF23 in AKI are still unclear. It is also not known whether reducing the level of circulating FGF23 could alleviate AKI or its poor prognosis. Here, we review the pathophysiological mechanism and possible regulation of FGF23 in AKI and discuss the possibility of using FGF23 as a therapeutic target.

15.
Front Cardiovasc Med ; 9: 982969, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36337861

RESUMO

Coronary heart disease (CHD) is a common comorbidity in intensive care unit (ICU) patients, particularly in the elderly. This particular population may have worse conditions during sepsis, and it presents an overwhelming challenge for clinical practice. Previous studies suggested that patients with CHD have an increased risk of cardiovascular events, and low albumin concentration worsens the prognosis of patients with stable CHD. Hypoalbuminemia in patients with sepsis is common due to nutritional disorders, excessive consumption, and leakage. Albumin is a fluid often used for resuscitation in patients with sepsis. However, albumin infusion in patients with sepsis and CHD has rarely been studied. The effects and safety of albumin infusion in patients with sepsis and CHD remain unclear. Therefore, we collected medical information from Mimic-III (Mimic-III) and compared the all-cause mortality and cardiovascular mortality at 28- or 90-day between the albumin and non-albumin groups in septic patients with CHD. A total of 2,027 patients with sepsis and CHD were included in our study, with 405 in the albumin group and 1,622 in the non-albumin group. After propensity score matching (PSM), 350 pairs were included in our study. Improved survival benefits were found in the albumin group at the 28-day all-cause mortality compared with the non-albumin group (hazard ratio [HR], 0.54; 95% CI: 0.38-0.78; p = 0.0009). However, no difference was detected in the 90-day survival benefits (HR, 0.80, 95% CI: 0.60-1.06, p = 0.1207). Albumin infusion did not reverse cardiovascular mortality neither at 28th day nor at 90th day (cardiovascular mortality: 28 days, HR, 0.52, 95% CI: 0.23-1.19, p = 0.1218; 90 days, HR, 0.66, 95% CI: 0.33-1.33, p = 0.2420).

16.
CNS Neurosci Ther ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377471

RESUMO

AIMS: Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments. However, the pathophysiology of SAE is complex and unclear. Here, we investigated the role of hippocampus (HPC)-prefrontal cortex (PFC) in cognitive dysfunction in sepsis induced by cecal ligation puncture (CLP) in mice. METHODS: The neural projections from the HPC to PFC were first identified via retrograde tracing and viral expression. Chemogenetic activation of the HPC-PFC pathway was shown via immunofluorescent staining of c-Fos-positive neurons in PFC. Morris Water Maze (MWM) and Barnes maze (BM) were used to evaluate cognitive function. Western blotting analysis was used to determine the expression of glutamate receptors and related molecules in PFC and HPC. RESULTS: Chemogenetic activation of the HPC-PFC pathway enhanced cognitive dysfunction in CLP-induced septic mice. Glutamate receptors mediated the effects of HPC-PFC pathway activation in CLP mice. The activation of the HPC-PFC pathway resulted in significantly increased levels of NMDAR, AMPAR, and downstream signaling molecules including CaMKIIa, pCREB, and BDNF in PFC. However, inhibition of glutamate receptors using 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo (F)quinoxaline (NBQX), which is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR inhibitor), or D-2-amino-5-phosphonopentanoate (D-AP5), which is an NMDA receptor antagonist abolished this increase. CONCLUSION: Our study reveals the important role of the HPC-PFC pathway in improving cognitive dysfunction in a mouse model of CLP sepsis and provides a novel pathogenetic mechanism for SAE.

17.
Materials (Basel) ; 15(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36363383

RESUMO

In this work, Gd2O3 bulks were sintered at temperatures ranging from 1400 °C to 1600 °C for times from 6 h to 24 h, and their microstructure and properties were studied for a wider application of materials in thermal barrier coatings. The densification of the Gd2O3 bulk reached 96.16% when it was sintered at 1600 °C for 24 h. The elastic modulus, hardness, fracture toughness and thermal conductivity of the bulks all increased with the rise in sintering temperature and extension of sintering time, while the coefficient of thermal expansion decreased. When the Gd2O3 bulk was sintered at 1600 °C for 24 h, it had the greatest elastic modulus, hardness, fracture toughness and thermal conductivity of 201.15 GPa, 9.13 GPa, 15.03 MPa·m0.5 and 2.75 W/(m·k) (at 1100 °C), respectively, as well as the smallest thermal expansion coefficients of 6.69 × 10-6/°C (at 1100 °C).

18.
Nat Commun ; 13(1): 7233, 2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36433980

RESUMO

Climate extremes cause significant winter wheat yield loss and can cause much greater impacts than single extremes in isolation when multiple extremes occur simultaneously. Here we show that compound hot-dry-windy events (HDW) significantly increased in the U.S. Great Plains from 1982 to 2020. These HDW events were the most impactful drivers for wheat yield loss, accounting for a 4% yield reduction per 10 h of HDW during heading to maturity. Current HDW trends are associated with yield reduction rates of up to 0.09 t ha-1 per decade and HDW variations are atmospheric-bridged with the Pacific Decadal Oscillation. We quantify the "yield shock", which is spatially distributed, with the losses in severely HDW-affected areas, presumably the same areas affected by the Dust Bowl of the 1930s. Our findings indicate that compound HDW, which traditional risk assessments overlooked, have significant implications for the U.S. winter wheat production and beyond.


Assuntos
Triticum , Vento , Estações do Ano , Clima , Mudança Climática
19.
Front Oncol ; 12: 1024915, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439512

RESUMO

Background: The role of ferroptosis in tumor progression and immune microenvironment is extensively investigated. However, the potential value of ferroptosis regulators in predicting prognosis and therapeutic strategies for osteosarcoma (OS) patients remains to be elucidated. Methods: Here, we extracted transcriptomic and survival data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) to investigate the expression and prognostic value of ferroptosis regulators in OS patients. After comprehensive analyses, including Gene set variation analysis (GSVA), single-sample gene-set enrichment analysis (ssGSEA), Estimated Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE), single-cell RNA sequencing, and biological experiments, our constructed 8-ferroptosis-regulators prognostic signature effectively predicted the immune landscape, prognosis, and chemoradiotherapy strategies for OS patients. Results: We constructed an 8-ferroptosis-regulators signature that could predict the survival outcome of OS. The signature algorithm scored samples, and high-scoring patients were more prone to worse prognoses. The tumor immune landscape suggested the positive relevance between risk score and immunosuppression. Interfering HILPDA and MUC1 expression would inhibit tumor cell proliferation and migration, and MUC1 might improve the ferroptosis resistance of OS cells. Moreover, we predicted chemoradiotherapy strategies of cancer patients following ferroptosis-risk-score groups. Conclusion: Dysregulated ferroptosis gene expression can affect OS progression by affecting the tumor immune landscape and ferroptosis resistance. Our risk model can predict OS survival outcomes, and we propose that HILPDA and MUC1 are potential targets for cancer therapy.

20.
Front Pediatr ; 10: 986500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440334

RESUMO

Objective: This study aims to explore the clinical value of artificial intelligence (AI)-assisted bone age assessment (BAA) among children with growth hormone deficiency (GHD). Methods: A total of 290 bone age (BA) radiographs were collected from 52 children who participated in the study at Sun Yat-sen Memorial Hospital between January 2016 and August 2017. Senior pediatric endocrinologists independently evaluated BA according to the China 05 (CH05) method, and their consistent results were regarded as the gold standard (GS). Meanwhile, two junior pediatric endocrinologists were asked to assessed BA both with and without assistance from the AI-based BA evaluation system. Six months later, around 20% of the images assessed by the junior pediatric endocrinologists were randomly selected to be re-evaluated with the same procedure half a year later. Root mean square error (RMSE), mean absolute error (MAE), accuracy, and Bland-Altman plots were used to compare differences in BA. The intra-class correlation coefficient (ICC) and one-way repeated ANOVA were used to assess inter- and intra-observer variabilities in BAA. A boxplot of BA evaluated by different raters during the course of treatment and a mixed linear model were used to illustrate inter-rater effect over time. Results: A total of 52 children with GHD were included, with mean chronological age and BA by GS of 6.64 ± 2.49 and 5.85 ± 2.30 years at baseline, respectively. After incorporating AI assistance, the performance of the junior pediatric endocrinologists improved (P < 0.001), with MAE and RMSE both decreased by more than 1.65 years (Rater 1: ΔMAE = 1.780, ΔRMSE = 1.655; Rater 2: ΔMAE = 1.794, ΔRMSE = 1.719), and accuracy increasing from approximately 10% to over 91%. The ICC also increased from 0.951 to 0.990. During GHD treatment (at baseline, 6-, 12-, 18-, and 24-months), the difference decreased sharply when AI was applied. Furthermore, a significant inter-rater effect (P = 0.002) also vanished upon AI involvement. Conclusion: AI-assisted interpretation of BA can improve accuracy and decrease variability in results among junior pediatric endocrinologists in longitudinal cohort studies, which shows potential for further clinical application.

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