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1.
Front Immunol ; 13: 973991, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081511

RESUMO

Impaired immune responses have been observed in patients with type-2 diabetes mellitus (T2DM), which increases susceptibility to tuberculosis infection. However, the effect of the tuberculosis infection on the immunological and metabolic features of T2DM is largely unknown. To investigate this question, age- and sex-matched patients with pulmonary tuberculosis (PTB), T2DM, or T2DM combined with PTB were recruited from the Infectious Disease Hospital of Heilongjiang Province between January and September 2020. Healthy subjects were used as controls. Cytokines and chemokines in fasting serum samples were determined using the Quantibody Inflammation Array. Compared with T2DM alone, patients with T2DM combined with PTB have higher fasting blood glucose levels and monocyte counts in circulation. Among the four groups, circulating IL-10 levels peaked in patients with T2DM and PTB (p<0.05). Univariate linear analysis showed that serum IL-10 levels were positively associated with myeloid cells but negatively correlated with lymphocyte counts in these patients (p<0.05). Serum IL-6 levels were 1.6-fold higher in patients with T2DM plus PTB than in those with T2DM alone. In conclusion, PTB infection in patients with T2DM had distinct inflammatory profiles and sustained hyperglycaemia compared with PTB or T2DM alone. IL-10 levels and elevated monocyte counts could be hallmarks of patients with T2DM infected with PTB.


Assuntos
Diabetes Mellitus Tipo 2 , Tuberculose Latente , Tuberculose Pulmonar , Tuberculose , Humanos , Interleucina-10
2.
Horm Metab Res ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36108658

RESUMO

This meta-analysis was conducted to investigate the association between MTHFR A1298C polymorphism and susceptibility to diabetic nephropathy. PubMed, Embase, Web of Science, Cochrane Library, China national knowledge infrastructure (CNKI) and China Wanfang database were searched for studies on the association between MTHFR A1298C single nucleotide polymorphism and susceptibility to diabetic nephropathy until May 2022. Data were analyzed by Stata 15.0 software. Odds ratio (OR) was used as the effect size. A total of 7 articles were identified, including 1287 cases in the diabetic nephropathy group and 1431 cases in the control group. The pooled OR of allele C at MTHFR A1298C was 1.28 (95%CI: 1.02-1.59, P= 0.03) compared with allele A. The pooled OR values of dominant, and heterozygous genetic models were 1.45 (95%CI: 1.13-1.86), and 1.42 (95%CI: 1.19-1.70), respectively, and the differences were all statistically significant. There was no statistical significance in the recessive (OR=1.06, 95%CI: 0.62-1.82), and homozygous gene inheritance models (OR=1.29, 95%CI: 0.72-2.31). In conclusion, MTHFR A1298C polymorphism is associated with susceptibility to diabetic nephropathy. Allele C, genotype CC+AC, and AC at MTHFR A1298C locus can increase the risk of diabetic nephropathy.

3.
Front Immunol ; 13: 936662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059447

RESUMO

Objective: Platelet (PLT) engages in immune and inflammatory responses, all of which are related to the prognosis of critically ill patients. Although thrombocytopenia at ICU admission contributes to in-hospital mortality, PLT is repeatedly measured during ICU hospitalization and the role of longitudinal PLT trajectory remains unclear. We aimed to identify dynamic PLT trajectory patterns and evaluate their relationships with mortality risk and thrombocytopenia. Methods: We adopted a three-phase, multi-cohort study strategy. Firstly, longitudinal PLT trajectory patterns within the first four ICU days and their associations with 28-day survival were tested in the eICU Collaborative Research Database (eICU-CRD) and independently validated in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Secondly, the relationships among PLT trajectory patterns, thrombocytopenia, and 28-day mortality were explored and validated. Finally, a Mortality GRade system for ICU dynamically monitoring patients (Mortality-GRID) was developed to quantify the mortality risk based on longitudinal PLT, which was further validated in the Molecular Epidemiology of Acute Respiratory Distress Syndrome (MEARDS) cohort. Results: A total of 35,332 ICU patients were included from three cohorts. Trajectory analysis clustered patients into ascending (AS), stable (ST), or descending (DS) PLT patterns. DS patients with high baseline PLT decline quickly, resulting in poor prognosis. AS patients have low baseline PLT but recover quickly, favoring a better prognosis. ST patients maintain low PLT, having a moderate prognosis in between (HR ST vs AS = 1.26, 95% CI: 1.14-1.38, P = 6.15 × 10-6; HR DS vs AS = 1.58, 95% CI: 1.40-1.79, P = 1.41 × 10-13). The associations remained significant in patients without thrombocytopenia during the entire ICU hospitalization and were robust in sensitivity analyses and stratification analyses. Further, the trajectory pattern was a warning sign of thrombocytopenia, which mediated 27.2% of the effects of the PLT trajectory on 28-day mortality (HR indirect = 1.11, 95% CI: 1.06-1.17, P = 9.80 × 10-6). Mortality-GRID well predicts mortality risk, which is in high consistency with that directly estimated in MEARDS (r = 0.98, P = 1.30 × 10-23). Conclusion: Longitudinal PLT trajectory is a complementary predictor to baseline PLT for patient survival, even in patients without risk of thrombocytopenia. Mortality-GRID could identify patients at high mortality risk.


Assuntos
Síndrome do Desconforto Respiratório , Trombocitopenia , Estudos de Coortes , Estado Terminal , Humanos , Unidades de Terapia Intensiva , Contagem de Plaquetas
4.
Comput Struct Biotechnol J ; 20: 4600-4617, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090815

RESUMO

Spatially resolved transcriptomics provides a new way to define spatial contexts and understand the pathogenesis of complex human diseases. Although some computational frameworks can characterize spatial context via various clustering methods, the detailed spatial architectures and functional zonation often cannot be revealed and localized due to the limited capacities of associating spatial information. We present RESEPT, a deep-learning framework for characterizing and visualizing tissue architecture from spatially resolved transcriptomics. Given inputs such as gene expression or RNA velocity, RESEPT learns a three-dimensional embedding with a spatial retained graph neural network from spatial transcriptomics. The embedding is then visualized by mapping into color channels in an RGB image and segmented with a supervised convolutional neural network model. Based on a benchmark of 10x Genomics Visium spatial transcriptomics datasets on the human and mouse cortex, RESEPT infers and visualizes the tissue architecture accurately. It is noteworthy that, for the in-house AD samples, RESEPT can localize cortex layers and cell types based on pre-defined region- or cell-type-enriched genes and furthermore provide critical insights into the identification of amyloid-beta plaques in Alzheimer's disease. Interestingly, in a glioblastoma sample analysis, RESEPT distinguishes tumor-enriched, non-tumor, and regions of neuropil with infiltrating tumor cells in support of clinical and prognostic cancer applications.

5.
Front Nutr ; 9: 976518, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091240

RESUMO

Background: Periodontitis is a chronic inflammatory disease of the oral cavity characterized by inflammation of the periodontal tissue and resorption of the alveolar bone, which has a high incidence and is the main cause of tooth loss in adults. In addition to its role in promoting osteogenesis, magnesium also has a role in regulating the inflammatory response, both systemically and locally. There is growing evidence that magnesium is an important factor in maintaining the normal functioning of the body's immune system. Hypomagnesaemia can lead to a variety of chronic inflammatory diseases throughout the body, including periodontitis. Two-thirds of the US population suffers from magnesium deficiency. The connection between dietary magnesium and periodontitis is unknown. As a result, we set out to investigate the link between dietary magnesium intake and periodontitis. Methods: In this study, we collected data from the National Health and Nutrition Examination Survey (NHANES) database from 2013 to 2014. Through 24-h dietary recalls, information about food consumption was collected. We examined the association between the dietary magnesium and periodontitis using multivariable logistic regression model. Based on odds ratios (OR) and 95% confidence intervals (CIs), a strong association was detected. Results: Multivariable logistic regression analysis showed that the OR for periodontitis comparing the highest to the lowest quintile of dietary magnesium intake was 0.69 (95% CIs = 0.52~0.92). The restricted cubic spline (RCS) analysis showed that the non-linear association between dietary magnesium and periodontitis was statistically significant and that dietary magnesium supplementation reduced the prevalence of periodontitis. Conclusion: Dietary magnesium intake is associated with the prevalence of periodontitis. Dietary magnesium deficiency increases the prevalence of periodontitis.

6.
Adv Sci (Weinh) ; : e2203510, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073821

RESUMO

Self-powered tactile sensor with versatile functions plays a significant role in the development of an intelligent human-machine interaction (HMI) system. Herein, a hybrid self-powered porous-structured tactile sensor (SPTS) is proposed by monolithically integrating a porous triboelectrification-induced electroluminescence (TIEL) component and a single-electrode triboelectric nanogenerator with the high charge generation in the bulk volume. At a low pressure of 10 kPa, TIEL intensity can be significantly improved by three times, which is superior to that in previous reports, with enhanced triboelectricity. Based on the enhancement brought by the porous structure and optimized parameters, the SPTS achieves significant sensing performance in both optical and electrical modes. To demonstrate the potential of practical applications, a programmable optical and electrical dual-mode HMI system is established based on SPTS to remotely control an intelligent vehicle and operate a computer game through identifying finger touch trajectories. This work not only contributes a new economical-effective methodology toward a high-performance tribo-induced self-powered tactile sensor but also facilitates the remote control of HMI with dual-mode functionality, which has broad potential applications in the fields of intelligent robots, augmented reality, flexible wearable electronics, and smart home.

7.
Front Neurol ; 13: 948727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36158962

RESUMO

This study aimed to discuss clinical characteristics, therapy, and antibody prevalence in epilepsy (APE) score for short-term, frequent epileptic seizures in children who are autoimmune-antibody negative and respond well to immunotherapy. The clinical characteristics, imaging manifestations, electrophysiology, and effective treatment plan of 9 children who met the above criteria were retrospectively analyzed in the Pediatric Neurology Department of Qilu Hospital at Shandong University from June 2019 to December 2021. All 9 patients (6 boys, 3 girls; aged 13 months-11 years and 5 months, median 3.5 years) had acute-onset seizures within 3 months. All had previous normal growth/development with no family history of disease. Seizure types were focal motor seizures (6), generalized tonic-clonic seizures (2), and generalized secondary-to-focal (1); occurred >10 times/day; and lasted <1 min/episode. Formal treatment with ≥2 types of antiseizure medicine (ASM) achieved an unsatisfactory effect. Cranial magnetic resonance imaging showed an abnormal result in 1 case. The APE score was ≥4 in 3 cases and <4 in 6 cases. All patients experienced symptomatic relief with immunotherapy; subsequently, 8 patients were free of recurrence and 1 had significantly reduced seizure frequency. Autoimmune antibody screening is recommended for children who were previously well and have acute-onset epilepsy; high frequency, short-duration seizures; no good response to 2 types of ASM; and other etiologic factors excluded, even with APE score <4. Even with negative autoimmune antibody results, the possibility of autoimmune epilepsy should be considered for urgent initiation of immunotherapy, which can achieve good results.

8.
World J Clin Oncol ; 13(8): 675-688, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36160462

RESUMO

BACKGROUND: Breast cancer (BC) is the most common malignant tumor in women. AIM: To investigate BC-associated hub genes to obtain a better understanding of BC tumorigenesis. METHODS: In total, 1203 BC samples were downloaded from The Cancer Genome Atlas database, which included 113 normal samples and 1090 tumor samples. The limma package of R software was used to analyze the differentially expressed genes (DEGs) in tumor tissues compared with normal tissues. The cluster Profiler package was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of upregulated and downregulated genes. Univariate Cox regression was conducted to explore the DEGs with statistical significance. Protein-protein interaction (PPI) network analysis was employed to investigate the hub genes using the CytoHubba plug-in of Cytoscape software. Survival analyses of the hub genes were carried out using the Kaplan-Meier method. The expression level of these hub genes was validated in the Gene Expression Profiling Interactive Analysis database and Human Protein Atlas database. RESULTS: A total of 1317 DEGs (fold change > 2; P < 0.01) were confirmed through bioinformatics analysis, which included 744 upregulated and 573 downregulated genes in BC samples. KEGG enrichment analysis indicated that the upregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, cell cycle, and the p53 signaling pathway (P < 0.01); and the downregulated genes were mainly enriched in the cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor signaling pathway, and AMP-activated protein kinase signaling pathway (P < 0.01). CONCLUSION: In view of the results of PPI analysis, which were verified by survival and expression analyses, we conclude that MAD2L1, PLK1, SAA1, CCNB1, SHCBP1, KIF4A, ANLN, and ERCC6L may act as biomarkers for the diagnosis and prognosis in BC patients.

9.
Am J Pathol ; 2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36174680

RESUMO

Ischemia-reperfusion (I/R) injury,aggravated by innate immune cell-mediated inflammatory response, is a major problem in liver transplantation. Stimulator of interferon gene (STING) is a crucial regulatory signal molecule in the DNA sensing pathway, and its activation can produce mighty innate immunity. However, the STING-mediated innate immune pathway in hepatic I/R injury has not been fully elucidated. In this study,we first examined the STING expression changes in the liver tissues of mice after hepatic I/R by quantitative polymerase chain reaction and Western blotting assays. Then we investigated the role of STING in I/R injury by using a murine hepatic I/R model. We demonstrated that STING up-regulation in mouse liver tissues in response to I/R injury and STING deficiency in myeloid cells could significantly ameliorate I/R induced liver injury and inflammatory responses. The use of STING inhibitors in hepatic I/R injury has also displayed a satisfactory outcome. Mechanically, inhibition of HIF-1α and enhancement of P-AMPK to reduce macrophage activation may be its protective effect on hepatic I/R injury. These findings revealed the potential regulatory effects of STING in hepatic I/R and provided a new method for clinical protection of hepatic I/R injury.

10.
Curr Pharm Des ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056848

RESUMO

BACKGROUND: Acute kidney injury (AKI) is closely linked to the pathogensis of sepsis. Oxidative stress can affect the development of AKI by increasing damage to renal tubular epithelial cells. Astragaloside IV (AS-IV), a natural saponin that is widly verifed beneficial for ameliorating sepsis-induced kidney injury. However, the underlying mechanisms of AS-IV on relieving oxidative stress in renal tubular epithelial cells are yet to be established. PURPOSE: We aimed to investigate whether AS-IV could attenuate mitochondrial dysfunction and apoptosis in renal tubular epithelial cells and reveal its underlying mechanisms. METHODS: For the in vivo study, mice were divided into four groups(n=6): sham+saline, CLP+saline, CLP+AS-IV-low dosage(5 mg/kg), CLP+AS-IV-high dosage(10 mg/kg), After 6 h or 24 h of treatment, the renal injuries were assessed based related parameters of blood, protein and histopathological examination. Immunohistochemistry and ELISA were used to examine renal function. The molecular mechanism of AS-IV inhibited apoptosis and mitochondrial damage were monitored by flow cytometry and western blot analysis in HK-2 cells. RESULTS: We found that AS-Ⅳ ameliorates renal vacuolization, brush border loss, mitochondrial ultrastructure changes in sepsis-induced AKI, and the apoptosis and oxidative damage were greatly mitigated by AS-Ⅳ(10 mg/kg)-treated group. Abnormal changes in mitochondrial morphology and mitochondrial membrane potential were alleviated, and the expression of mitochondrial complex protein Ⅰ (NDUFB8) and mitochondrial complex protein Ⅱ (SDHB8) increased with (10 mg/kg)-treated group. Tubular epithelial cell apoptosis in AS-Ⅳ(20 µM)-treated cells was reduced by the Bax and cleaved caspase3 pathway. CONCLUSION: These study demonstrated that AS-IV protects against sepsis-induced kidney tubular injury by alleviating oxidative stress, mitochondrial dysfunction possibly associated with the restored cleaved caspase3 pathway.

11.
Transl Cancer Res ; 11(8): 2823-2833, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36093551

RESUMO

Background: This study aimed to systematically evaluate and compare the diagnostic value of bubble lucency, interface, lobulated margin and spiculation in distinguishing early invasive and preinvasive intrapulmonary ground-glass nodules (GGNs) using evidence-based meta-analysis methods. Dual low-dose targeted perfusion computed tomography (CT) imaging is controversial in the diagnosis of invasive and preinvasive ground-glass nodules. Different studies have different views and opinions. Therefore, it is necessary to conduct a systematic review of this subject in the form of meta-analysis to guide clinical diagnosis and treatment. Methods: PubMed, Web of Science, Cochrane library and Embase were searched for recent documentation on the diagnostic value of different signs in invasive and preinvasive pulmonary GGNs. CT imaging signs of bubble lucency, speculation, interface, lobulated margin, and spiculation were used as diagnostic references to discriminate pre-invasive and invasive disease. The sensitivity, specificity, summary receiver operating characteristic (SROC) curves, and the area under the SROC curve (AUC) were calculated to evaluate diagnostic efficiency. Results: The diagnostic sensitivity and specificity using bubble lucency as a reference of invasive ground-glass opacity (GGO) discrimination was 0.33 (0.24-0.44) and 0.74 (0.62-0.83) respectively. For interface, lobulated margin, and speculation, the diagnostic sensitivity were 0.30 (0.21-0.41), 0.49 (0.39-0.60) and 0.22 (0.14-0.33); and the specificity were 0.83 (0.74-0.89), 0.66 (0.49-0.80) and 0.86 (0.67-0.95). The pooled ROC curve was drawn by sensitivity against 1-specificity using Stata version 15.0. The area under the ROC curve (AUC) values were 0.53, 0.60, 0.58, and 0.43 for bubble lucency, speculation, lobulated margin, and pleural indentation of GGO for discriminating pre-invasive and invasive disease. Conclusions: The diagnostic value of a single CT imaging sign of GGO, such as bubble lucency, speculation, interface, lobulated margin, and spiculation is limited for discriminating pre-invasive and invasive disease because of low sensitivity, specificity, and AUC.

12.
Front Pharmacol ; 13: 962525, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081936

RESUMO

Hepatic fibrosis (HF) refers to the pathophysiological process of connective tissue dysplasia in the liver caused by various pathogenic factors. Nowadays, HF is becoming a severe threat to the health of human being. However, the drugs available for treating HF are limited. Currently, increasing natural agents derived from traditional Chinese medicines (TCMs) have been found to be beneficial for HF. A systemic literature search was conducted from PubMed, GeenMedical, Sci-Hub, CNKI, Google Scholar and Baidu Scholar, with the keywords of "traditional Chinese medicine," "herbal medicine," "natural agents," "liver diseases," and "hepatic fibrosis." So far, more than 76 natural monomers have been isolated and identified from the TCMs with inhibitory effect on HF, including alkaloids, flavones, quinones, terpenoids, saponins, phenylpropanoids, and polysaccharides, etc. The anti-hepatic fibrosis effects of these compounds include hepatoprotection, inhibition of hepatic stellate cells (HSC) activation, regulation of extracellular matrix (ECM) synthesis & secretion, regulation of autophagy, and antioxidant & anti-inflammation, etc. Natural compounds and extracts from TCMs are promising agents for the prevention and treatment of HF, and this review would be of great significance to development of novel drugs for treating HF.

13.
Adv Sci (Weinh) ; : e2202706, 2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36031409

RESUMO

Emerging evidence emphasizes the functional impacts of host microbiome on the etiopathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). However, there are limited mechanistic insights into the contribution of microbial biomolecules especially microbial peptides toward modulating immune homeostasis. Here, by mining the metagenomics data of tonsillar microbiome, a deficiency of the encoding genes of lantibiotic peptides salivaricins in RA patients is identified, which shows strong correlation with circulating immune cells. Evidence is provided that the salivaricins exert immunomodulatory effects in inhibiting T follicular helper (Tfh) cell differentiation and interleukin-21 (IL-21) production. Mechanically, salivaricins directly bind to and induce conformational changes of IL-6 and IL-21 receptors, thereby inhibiting the bindings of IL-6 and IL-21 to their receptors and suppressing the downstream signaling pathway. Finally, salivaricin administration exerts both prophylactic and therapeutic effects against experimental arthritis in a murine model of RA. Together, these results provide a mechanism link of microbial peptides-mediated immunomodulation.

14.
World J Clin Cases ; 10(19): 6602-6608, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35979314

RESUMO

BACKGROUND: Congenital complete heart block (CCHB) with normal cardiac structure and negativity for anti-Ro/La antibody is rare. Additionally, CCHB is much less frequently diagnosed in adults, and its natural history in adults is less well known. CASE SUMMARY: A 23-year-old woman was admitted to our hospital for frequent syncopal episodes. She had bradycardia at the age of 1 year but had never had impaired exercise capacity or a syncopal episode before admission. The possible diagnosis of acquired complete atrioventricular block was carefully ruled out, and then the diagnosis of CCHB was made. According to existing guidelines, permanent pacemaker implantation was recommended, but the patient declined. With regular follow-up for 28 years, the patient had an unusually good outcome without any invasive intervention or medicine. She had an uneventful pregnancy and led a normally active life without any symptoms of low cardiac output or syncopal recurrence. CONCLUSION: This case implies that CCHB in adulthood may have good clinical outcomes and does not always require permanent pacemaker implantation.

15.
Int J Epidemiol ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947762

RESUMO

OBJECTIVE: COVID-19 in post-partum women is commonly overlooked. The present study assessed whether puerperium is an independent risk factor of COVID-19 related in-hospital maternal death and whether fatality is preventable in the Brazilian context. METHODS: We retrospectively studied the clinical data of post-partum/pregnant patients hospitalized with COVID-19 gathered from a national database that registered severe acute respiratory syndromes (SIVEP-Gripe) in Brazil. Logistic regressions were used to examine the associations of in-hospital mortality with obstetric status and with the type of public healthcare provider, adjusting for socio-demographic, epidemiologic, clinical and healthcare-related measures. RESULTS: As of 30 November 2021, 1943 (21%) post-partum and 7446 (79%) pregnant patients of age between 15 and 45 years with COVID-19 that had reached the clinical endpoint (death or discharge) were eligible for inclusion. Case-fatality rates for the two groups were 19.8% and 9.2%, respectively. After the adjustment for covariates, post-partum patients had almost twice the odds of in-hospital mortality compared with pregnant patients. Patients admitted to private (not-for-profit) hospitals, those that had an obstetric centre or those located in metropolitan areas were less likely to succumb to SARS-CoV-2 infection. Those admitted to the Emergency Care Unit had similar mortality risk to those admitted to other public healthcare providers. CONCLUSION: We demonstrated that puerperium was associated with an increased odds of COVID-19-related in-hospital mortality. Only part of the risk can be reduced by quality healthcare such as non-profit private hospitals, those that have an obstetric centre or those located in urban areas.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(4): 1071-1078, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-35981364

RESUMO

OBJECTIVE: To investigate the expression of CD47 molecules in patients with newly diagnosis of adult acute myeloid leukemia (AML) and its correlation with clinical prognosis. METHODS: 20 patients with acute myeloid leukemia diagnosed in Shanghai Fengxian District Central hospital from April 2020 to October 2021 and 5 cases with non malignant hematological diseases in the control group were collected, and the expression of CD47 in single nuclear cells of bone marrow and peripheral blood was detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). Combined with the blood image, bone marrow smears, flow cytometry, chromosome and gene detection, ECOG score, etc. during the patient's initial diagnosis, the relationship between the patient's prognosis and CD47 was evaluated. RESULTS: The expression of CD47 in bone marrow (P=0.0115) and peripheral blood mononuclear cells (P=0.0069) in new diagnosis AML patients was significantly higher than that of controls. In bone marrow mononuclear cells, the total survival time of patients with high CD47 expression was less than that of CD47 low expression patients (P=0.036). There was statistical significance in difference stratification group (P=0.012), but there was no statistical significance between CD47 expression and survival time in peripheral blood mononuclear cells (P=0.116). There were no statistical significance between bone marrow mononuclear cell CD47 expression and gene mutation fusion genes related to leukemia , CD34+, CD38+, CD123+ (P>0.05). The proportion of bone marrow protocells in AML patients was >50%, the ECOG score was >2 points, MLLELL fusion gene and chromosome prognosis stratification were all risk factors affecting the survival of patients (P=0023, 0.036, 0.012, 0.001, respectively). The high expression of bone marrow CD47 in AML patients indicated a high risk of recurrence (P=0.017). CONCLUSION: The high expression of bone marrow mononuclear cell CD47 in AML patients indicates poorer survival and higher risk of recurrence.


Assuntos
Antígeno CD47 , Leucemia Mieloide Aguda , Adulto , China , Humanos , Leucemia Mieloide Aguda/genética , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Prognóstico
17.
Nutrients ; 14(14)2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35889856

RESUMO

Zinc deficiency could lead to a dynamic variation in gut microbial composition and function in animals. However, how zinc deficiency affects the gut microbiome in school-age children remains unclear. The purpose of this study was to profile the dynamic shifts in the gut microbiome of school-age children with zinc deficiency, and to determine whether such shifts are associated with dietary intake. A dietary survey, anthropometric measurements, and serum tests were performed on 177 school-age children, and 67 children were selected to explore the gut microbial community using amplicon sequencing. School-age children suffered from poor dietary diversity and insufficient food and nutrient intake, and 32% of them were zinc deficient. The inflammatory cytokines significantly increased in the zinc deficiency (ZD) group compared to that in the control (CK) group (p < 0.05). There was no difference in beta diversity, while the Shannon index was much higher in the ZD group (p < 0.05). At the genus level, Coprobacter, Acetivibrio, Paraprevotella, and Clostridium_XI were more abundant in the ZD group (p < 0.05). A functional predictive analysis showed that the metabolism of xenobiotics by cytochrome P450 was significantly depleted in the ZD group (p < 0.05). In conclusion, gut microbial diversity was affected by zinc deficiency with some specific bacteria highlighted in the ZD group, which may be used as biomarkers for further clinical diagnosis of zinc deficiency.


Assuntos
Microbioma Gastrointestinal , Desnutrição , Animais , Bactérias/genética , Dieta , Humanos , Zinco
18.
Front Oncol ; 12: 861412, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35847903

RESUMO

Background: Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. Chinese cases of GC account for about 40% of the global rate, with approximately 1.66 million people succumbing to the disease each year. Despite the progress made in the treatment of GC, most patients are diagnosed at an advanced stage due to the lack of obvious clinical symptoms in the early stages of GC, and their prognosis is still very poor. The m7G modification is one of the most common forms of base modification in post-transcriptional regulation, and it is widely distributed in the 5' cap region of tRNA, rRNA, and eukaryotic mRNA. Methods: RNA sequencing data of GC were downloaded from The Cancer Genome Atlas. The differentially expressed m7G-related genes in normal and tumour tissues were determined, and the expression and prognostic value of m7G-related genes were systematically analysed. We then built models using the selected m7G-related genes with the help of machine learning methods.The model was then validated for prognostic value by combining the receiver operating characteristic curve (ROC) and forest plots. The model was then validated on an external dataset. Finally, quantitative real-time PCR (qPCR) was performed to detect gene expression levels in clinical gastric cancer and paraneoplastic tissue. Results: The model is able to determine the prognosis of GC samples quantitatively and accurately. The ROC analysis of model has an AUC of 0.761 and 0.714 for the 3-year overall survival (OS) in the training and validation sets, respectively. We determined a correlation between risk scores and immune cell infiltration and concluded that immune cell infiltration affects the prognosis of GC patients. NUDT10, METTL1, NUDT4, GEMIN5, EIF4E1B, and DCPS were identified as prognostic hub genes and potential therapeutic agents were identified based on these genes. Conclusion: The m7G-related gene-based prognostic model showed good prognostic discrimination. Understanding how m7G modification affect the infiltration of the tumor microenvironment (TME) cells will enable us to better understand the TME's anti-tumor immune response, and hopefully guide more effective immunotherapy methods.

19.
Exp Lung Res ; 48(4-6): 158-167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903964

RESUMO

Background: Radiation-induced pulmonary fibrosis (RIPF) is a serious complication in patients treated with transthoracic irradiation. To date, there are no effective drugs for RIPF treatment. In this study, we attempted to explore the function of miR-761 in RIPF, further investigate its potential mechanism and evaluate its effectiveness in the treatment of RIPF. Methods: qRT-PCR analysis was used to detect miR-761 and peroxisome proliferator-activated receptor gamma (PPARg) coactivator-1 (PGC-1α) expression. Western Blot (WB) assay was applied to verify the regulation of PGC-1α by miR-761 and the expression of fibrosis-related proteins. Gel contraction assay was performed to demonstrate the level of fibroblast activation in vitro. A mouse RIPF model was used to validate the anti-fibrotic effect of Antagomir761. Bioinformatics analysis and dual-luciferase reporter assays were utilized to confirm the regulation relationship between miR-761 and PGC-1α. Results: The results showed that miR-761 was significantly elevated in irradiated mice lungs and fibroblasts. Overexpression of miR-761 in vitro promoted fibroblast activation. Whereas inhibition of miR-761 attenuated the degree of RIPF and inhibited fibroblast activation. Mechanistically, PGC-1α was a direct and functional target of miR-761, overexpression of PGC-1α inhibited irradiation-induced fibroblast activation, and knockdown of PGC-1α caused miR-761 inhibitor loses its anti-activation ability in irradiated cells. Conclusion: Our findings demonstrated that miR-761 regulated RIPF by targeting PGC-1α. Inhibition of miR-761 restored PGC-1α expression and attenuated RIPF damage, and miR-761 was a potential target for preventing the development of RIPF.


Assuntos
MicroRNAs , Fibrose Pulmonar , Animais , Regulação para Baixo , Fibrose , Pulmão/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fibrose Pulmonar/genética
20.
Front Nutr ; 9: 921037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811983

RESUMO

Objectives: The first objective of this study was to probe the effects of genkwanin (GKA) on osteoclast. The second goal of this study was to study whether GKA can protect lipopolysaccharide (LPS) and ovariectomized (OVX) induced bone loss. Materials and Methods: Various concentrations of GKA (1 and 10 mg/kg) were injected into mice. Different concentrations of GKA (1 and 5 µM) were used to detect the effects of GKA on osteoclast and osteoblast. Key Findings: GKA attenuated the osteoclast differentiation promoted by RANKL and expression of marker genes containing c-fos, ctsk as well as bone resorption related gene Trap and to the suppression of MAPK signaling pathway. In addition, GKA induced BMMs cell apoptosis in vitro. Moreover, GKA prevented LPS-induced and ovariectomized-induced bone loss in mice. Conclusion: Our research revealed that GKA had a potential to be an effective therapeutic agent for osteoclast-mediated osteoporosis.

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