Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 457
Filter
1.
Front Psychiatry ; 15: 1310118, 2024.
Article in English | MEDLINE | ID: mdl-38690201

ABSTRACT

Introduction: The present study aimed to investigate the effect of resilience on sleep quality and explore the role of social support between resilience and sleep quality in cancer patients. Methods: A multicenter and cross-sectional study was conducted in China from May to November 2021. A total of 202 cancer patients were recruited to complete the questionnaires composed of demographic information, Pittsburg Sleep Quality Index (PSQI), Resilience Scale-14 (RS-14), and Multidimensions Scale of Perceived Social Support (MSPSS). The associations between resilience, social support, and sleep quality were explored through hierarchical regression analysis. Results: The prevalence of poor sleep quality was 50% among cancer patients. Resilience, social support, and the interaction between resilience and social support were all found to be significantly associated with sleep quality. Results of simple slope analysis indicated that the association between resilience and sleep quality were gradually decreased with the increasing social support levels (1 SD below the mean, B=-0.225, ß=-0.551, P<0.001), mean social support (B=-0.147, ß=-0.353, P<0.001) and high social support (1 SD above the mean, B=-0.065, ß=-0.156, P<0.001). Additionally, social support mediated the effect of resilience on sleep quality among cancer patients. Discussion: Poor sleep quality has been common in cancer patients. Social support could mediate and alleviate the relationship between resilience and sleep quality among cancer patients. Besides providing sufficient social support, interventions based on resilience should be applied to address sleep problems in cancer patients.

2.
J Asthma ; : 1-11, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647486

ABSTRACT

Objective: This study aims to explore the effect of YiQi GuBen capsule on improving mitochondrial dysfunction in an animal model of asthma.Methods: The mice (n = 8) were divided into four groups including control (NC), ovalbumin (OVA), dexamethasone (OVA + DEX), and YiQi GuBen (OVA + YQGB) groups. Firstly, we established an OVA-induced mouse asthma model except for the NC group, which then were treated with dexamethasone and YiQi GuBen capsule. Subsequently, HE staining and Masson staining were used for pathological analysis of mice lung tissues. Next, we used transmission electron microscopy (TEM) to observe the effect of the Yiqi Guben capsule on the ultrastructure of mitochondria. Flow cytometry was used to analyze the ROS level, membrane potential, and the number of mitochondria in lung tissue. Moreover, we analyzed the copy number of mitochondrial DNA (mtDNA) and the expression levels of activator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and mitochondrial transcription factor A (TFAM).Results: The results of the pathological analysis showed that after treatment with the YiQi GuBen capsule, the lung tissue damage was significantly reduced. In addition, we observed that the ultrastructural damage of mitochondria was improved. Flow cytometry proved that after treatment with the YiQi GuBen capsule, the level of ROS in the mitochondria was effectively reduced, while the mitochondrial membrane potential decreased and the number increased significantly. Moreover, we found that the copy number of mtDNA was significantly increased and the expression levels of PGC-1α and TFAM were significantly upgraded.Conclusion: This study suggests YiQi GuBen capsule can effectively improve mitochondrial dysfunction in the OVA-induced mouse model.

3.
Immunol Cell Biol ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38650445

ABSTRACT

Unraveling the complexities of T cell aging is essential for developing targeted interventions to enhance immune function in the elderly. This article for the Highlights of 2023 Series integrates recent findings published in 2023, offering a panoramic view of the current understanding of T cell aging and its implications.

4.
BMC Cancer ; 24(1): 398, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553681

ABSTRACT

BACKGROUND: Cancer-related fatigue (CRF) is considered one of the most prevalent and distressing symptoms among cancer patients and may vary among patients with different cancer types. However, few studies have explored the influence of physical and psychological symptoms on CRF among esophageal cancer (EC) patients without esophagectomy. Therefore, this study aimed to examine the effects of physical and psychological symptoms on CRF among EC patients without esophagectomy. METHODS: In the present study, a cross-sectional study was conducted from February 2021 to March 2022 in Liaoning Province, China. Among the 112 included participants, 97 completed our investigation. The questionnaires used consisted of the Brief Fatigue Inventory (BFI), the MD Anderson Symptom Inventory Gastrointestinal Cancer Module (MDASI-GI), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), and demographic and clinical information. Multivariate linear regression was conducted to test the relationships between physical and psychological symptoms and CRF. RESULTS: Of the 97 EC patients, 60.8% reported CRF (BFI ≥ 4). The mean age of the participants was 64.92 years (SD = 8.67). According to the regression model, all the variables explained 74.5% of the variance in CRF. Regression analysis indicated that physical symptoms, including constipation, diarrhoea, and difficulty swallowing, contributed to CRF. On the other hand, depressive symptoms increased the level of CRF among EC patients without esophagectomy. CONCLUSIONS: Given the high prevalence of CRF among EC patients without esophagectomy, it is urgent to emphasize the importance of fatigue management interventions based on physical and psychological symptoms to alleviate CRF in EC patients.


Subject(s)
Esophageal Neoplasms , Neoplasms , Humans , Middle Aged , Aged , Cross-Sectional Studies , Esophageal Neoplasms/complications , Esophageal Neoplasms/epidemiology , Surveys and Questionnaires , Regression Analysis , Fatigue/epidemiology , Fatigue/etiology , Fatigue/diagnosis , Quality of Life
5.
J Exp Clin Cancer Res ; 43(1): 72, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38454445

ABSTRACT

BACKGROUND: The paucity of reliable biomarkers for predicting immunotherapy efficacy in patients with advanced hepatocellular carcinoma (HCC) has emerged as a burgeoning concern with the expanding use of immunotherapy. This study endeavors to delve into the potential peripheral biomarkers capable of prognosticating efficacy in HCC patients who are poised to receive anti-PD-1 monotherapy within the phase III clinical trial, KEYNOTE394. Additionally, we sought to elucidate the underlying molecular mechanisms for resistance to immune checkpoint blockade (ICB) and propose innovative combination immunotherapy strategies for future clinical application. METHODS: Patient blood samples were collected for single-cell RNA sequencing to evaluate the immune cell signature before receiving ICB therapy. Subsequently, in vitro assays and in vivo murine model experiments were conducted to validate the mechanism that S100A9+CD14+ monocytes play a role in ICB resistance. RESULTS: Our study demonstrates a notable enrichment of S100A9+CD14+ monocytes in the peripheral blood of patients exhibiting suboptimal responses to anti-PD-1 therapy. Moreover, we identified the Mono_S100A9 signature as a predictive biomarker, indicative of reduced efficacy in immunotherapy and decreased survival benefits across various tumor types. Mechanistically, S100A9 activates PD-L1 transcription by directly binding to the CD274 (PD-L1) gene promoter, thereby suppressing T-cell proliferation and cytotoxicity via the PD-1/PD-L1 axis, consequently diminishing the therapeutic effectiveness of subsequent anti-PD-1 treatments. Furthermore, our in vivo studies revealed that inhibiting S100A9 can synergistically enhance the efficacy of anti-PD-1 drugs in the eradication of hepatocellular carcinoma. CONCLUSIONS: Our study underscores the significance of S100A9+CD14+ monocytes in predicting inadequate response to ICB treatment and provides insights into the monocyte cell-intrinsic mechanisms of resistance to ICB therapy. We also propose a combined therapeutic approach to enhance ICB efficacy by targeting S100A9.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Monocytes/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , B7-H1 Antigen/metabolism , T-Lymphocytes/metabolism , Immunotherapy , Tumor Microenvironment , Calgranulin B/metabolism
6.
Medicine (Baltimore) ; 103(12): e37568, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38518056

ABSTRACT

BACKGROUND: Tic disorder is a common neurodevelopmental disorder in childhood, characterized primarily by motor or vocal tics. However, there is no systematic evaluation of pediatric massage therapy for children with Tic disorder. This study aims to evaluate the effectiveness and safety of massage therapy for children with tic disorder through a comprehensive meta-analysis and systematic review. METHODS: We systematically searched relevant randomized controlled trials from various databases such as CBM, CNKI, VIP, Wanfang database, PubMed, Embase, Web of Science, Cochrane Library, and SINOMED, published up to October 2023. To collect randomized controlled trials on pediatric massage therapy or in combination with other therapies for the treatment of tic disorders in children. The risk of bias in the included articles was assessed using the Cochrane guideline. Meta-analyses were performed using Review Manager 5.4, and publication bias was evaluated by using Begg test and Egger test in Stata SE software. RESULTS: This meta-analysis included 19 randomized controlled trials with 1423 patients. Pediatric massage therapy alone or in combination with conventional medication demonstrated a significant increase in clinical effectiveness rates [risk ratios = 1.15, 95% confidence interval [CI] (1.10, 1.20), Z = 6.54, P < .001], and reduced Yale Global Tie Severity Scale scores [standardized mean difference = -0.85, 95% CI (-1.50, -0.19), Z = 2.54, P = .01] and traditional Chinese medicine syndrome scores [standardized mean difference = -1.35, 95%CI (-2.08, -0.63), Z = 3.66, P = .0002]. In terms of adverse reactions, there was no statistical difference between the experimental and control groups [risk ratios = 0.26, 95% CI (0.14, 0.49), Z = 4.25, P < .001]. The Begg test and Egger test results indicated no publication bias. CONCLUSION: Evidence suggests that pediatric massage therapy is effective in improving tic disorders in children.


Subject(s)
Tic Disorders , Humans , Child , Randomized Controlled Trials as Topic , Tic Disorders/therapy , Massage/methods , Medicine, Chinese Traditional , Treatment Outcome
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 53(1): 64-72, 2024 Jan 19.
Article in English, Chinese | MEDLINE | ID: mdl-38426692

ABSTRACT

Hepatocellular carcinoma (HCC) is a serious neoplastic disease with increasing incidence and mortality, accounting for 90% of all liver cancers. Hepatitis viruses are the major causative agents in the development of HCC. Hepatitis A virus (HAV) primarily causes acute infections, which is associated with HCC to a certain extent, as shown by clinicopathological studies. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections lead to persistent liver inflammation and cirrhosis, disrupt multiple pathways associated with cellular apoptosis and proliferation, and are the most common viral precursors of HCC. Mutations in the HBV X protein (HBx) gene are closely associated with the incidence of HCC, while the expression of HCV core proteins contributes to hepatocellular lipid accumulation, thereby promoting tumorigenesis. In the clinical setting, hepatitis D virus (HDV) frequently co-infects with HBV, increasing the risk of chronic hepatitis. Hepatitis E virus (HEV) usually causes acute infections. However, chronic infections of HEV have been increasing recently, particularly in immuno-compromised patients and organ transplant recipients, which may increase the risk of progression to cirrhosis and the occurrence of HCC. Early detection, effective intervention and vaccination against these viruses may significantly reduce the incidence of liver cancer, while mechanistic insights into the interplay between hepatitis viruses and HCC may facilitate the development of more effective intervention strategies. This article provides a comprehensive overview of hepatitis viruses and reviews recent advances in research on aberrant hepatic immune responses and the pathogenesis of HCC due to viral infection.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B, Chronic , Hepatitis B , Hepatitis C , Hepatitis, Viral, Human , Liver Neoplasms , Humans , Liver Neoplasms/genetics , Hepatitis B, Chronic/complications , Hepatitis B/complications , Hepatitis, Viral, Human/complications , Hepatitis C/complications , Liver Cirrhosis/complications
8.
ACS Nano ; 18(10): 7485-7495, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38415599

ABSTRACT

Homovanillic acid (HVA) is a major dopamine metabolite, and blood HVA is considered as central nervous system (CNS) dopamine biomarker, which reflects the progression of dopamine-associated CNS diseases and the behavioral response to therapeutic drugs. However, facing blood various active substances interference, particularly structurally similar catecholamines and their metabolites, real-time and accurate monitoring of blood HVA remains a challenge. Herein, a highly selective implantable electrochemical fiber sensor based on a molecularly imprinted polymer is reported to accurately monitor HVA in vivo. The sensor exhibits high selectivity, with a response intensity to HVA 12.6 times greater than that of catecholamines and their metabolites, achieving 97.8% accuracy in vivo. The sensor injected into the rat caudal vein tracked the real-time changes of blood HVA, which paralleled the brain dopamine fluctuations and indicated the behavioral response to dopamine increase. This study provides a universal design strategy for improving the selectivity of implantable electrochemical sensors.


Subject(s)
Catecholamines , Dopamine , Rats , Animals , Homovanillic Acid/metabolism , Brain/metabolism
9.
ACS Appl Mater Interfaces ; 16(9): 11914-11929, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38383343

ABSTRACT

Conductive hydrogels have shown promising application prospects in the field of flexible sensors, but they often suffer from poor mechanical properties, low sensitivity, and lack of frost resistance. Herein, we report a tough, highly sensitive, and antifreeze strain sensor assembled from a conductive organohydrogel composed of a dual-cross-linked polyacrylamide and poly(vinyl alcohol) (PVA) network, as well as MXene nanosheets as nanofillers and poly(3,4-ethylenedioxythiophene)-doped poly(styrenesulfonate) (PEDOT/PSS) as the main conducting component (PPMP-OH organohydrogel). The tensile strength and toughness of PPMP-OH had been greatly enhanced by MXene nanosheets due to the mechanical reinforcement of MXene nanosheets, as well as various strong noncovalent interactions formed in the organohydrogels. The PPM1P-OH organohydrogels showed a tensile strength of 1.48 MPa at 772% and a toughness of 5.59 MJ/m3. Moreover, the conductivity and strain-sensing performance of PPMP-OH were significantly improved by PEDOT/PSS, which can form hydrogen bonds with PVA and electrostatic interactions with MXene. This was greatly beneficial for constructing a uniformly distributed and stable 3D conductive network and helped to obtain strain-dependent resistance of PPMP-OH. The strain sensors assembled from PPMP1-OH exhibited a high sensitivity of 5.16, a wide range of detectable strains up to 500%, and a short response time of 122 ms, which can effectively detect various physiological activities of the human body with high stability. In addition, the corresponding pressure sensor array also showed high sensitivity in identifying pressure magnitude and position.

10.
World J Gastroenterol ; 30(4): 346-366, 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38313238

ABSTRACT

BACKGROUND: Extreme heat exposure is a growing health problem, and the effects of heat on the gastrointestinal (GI) tract is unknown. This study aimed to assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. AIM: To assess the incidence of GI symptoms associated with heatstroke and its impact on outcomes. METHODS: Patients admitted to the intensive care unit (ICU) due to heatstroke were included from 83 centres. Patient history, laboratory results, and clinically relevant outcomes were recorded at ICU admission and daily until up to day 15, ICU discharge, or death. GI symptoms, including nausea/vomiting, diarrhoea, flatulence, and bloody stools, were recorded. The characteristics of patients with heatstroke concomitant with GI symptoms were described. Multivariable regression analyses were performed to determine significant predictors of GI symptoms. RESULTS: A total of 713 patients were included in the final analysis, of whom 132 (18.5%) patients had at least one GI symptom during their ICU stay, while 26 (3.6%) suffered from more than one symptom. Patients with GI symptoms had a significantly higher ICU stay compared with those without. The mortality of patients who had two or more GI symptoms simultaneously was significantly higher than that in those with one GI symptom. Multivariable logistic regression analysis revealed that older patients with a lower GCS score on admission were more likely to experience GI symptoms. CONCLUSION: The GI manifestations of heatstroke are common and appear to impact clinically relevant hospitalization outcomes.


Subject(s)
Gastrointestinal Diseases , Heat Stroke , Humans , Retrospective Studies , Critical Illness , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology , Intensive Care Units , Heat Stroke/complications , Heat Stroke/epidemiology
11.
J Struct Biol X ; 9: 100097, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38361954

ABSTRACT

Aquaporin Z (AqpZ), a bacterial water channel, forms a tetrameric complex and, like many other membrane proteins, activity is regulated by lipids. Various methods have been developed to facilitate structure determination of membrane proteins, such as the use of antibodies. Here, we graft onto AqpZ the ALFA tag (AqpZ-ALFA), an alpha helical epitope, to make use of the high-affinity anti-ALFA nanobody (nB). Native mass spectrometry reveals the AqpZ-ALFA fusion forms a stable, 1:1 complex with nB. Single-particle cryogenic electron microscopy studies reveal the octameric (AqpZ-ALFA)4(nB)4 complex forms a dimeric assembly and the structure was determined to 1.9 Å resolution. Dimerization of the octamer is mediated through stacking of the symmetrically bound nBs. Tube-like density is also observed, revealing a potential cardiolipin binding site. Grafting of the ALFA tag, or other epitope, along with binding and association of nBs to promote larger complexes will have applications in structural studies and protein engineering.

13.
ACS Omega ; 9(1): 2000-2011, 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38222569

ABSTRACT

The increase in the styrene content in styrene-butadiene rubber (SBR) can improve the abrasion performance and cutting resistance of rubber, which has received attention in the tire industry. The fatigue performance is the main evaluation index of rubber materials applied to tires. In this study, the effect of the styrene content and its interaction with carbon black (CB) on the dynamic fatigue performance and mechanism of SBR were investigated. The results indicated that the dynamic fatigue life of the rubber composite materials was prolonged with increasing styrene content; furthermore, it showed a trend of increasing and then decreasing with increasing CB content. At a certain CB content, styrene and CB displayed a synergistic effect on improving the dynamic fatigue life of the composite materials. The dynamic fatigue performance of SBR40/CB20 was the best. The expansion of the fatigue cracks followed the secondary cracking mechanism, which consumed a large amount of strain energy and slowed the development of the main crack. However, when the CB content exceeded 40 phr, the mechanism transformed to main crack self-propagation and the fatigue life decreased.

14.
Nat Commun ; 15(1): 346, 2024 Jan 06.
Article in English | MEDLINE | ID: mdl-38184688

ABSTRACT

Pendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO3-) exchange for chloride (Cl-) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin also exports iodide (I-) in the thyroid gland. Pendrin mutations in humans lead to Pendred syndrome, causing hearing loss and goiter. Inhibition of pendrin is a validated approach for attenuating airway hyperresponsiveness in asthma and for treating hypertension. However, the mechanism of anion exchange and its inhibition by drugs remains poorly understood. We applied cryo-electron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl-, I-, HCO3- or in the apo-state. The structures reveal two anion-binding sites in each protomer, and functional analyses show both sites are involved in anion exchange. The structures also show interactions between the Sulfate Transporter and Anti-Sigma factor antagonist (STAS) and transmembrane domains, and mutational studies suggest a regulatory role. We also determine the structure of pendrin in a complex with niflumic acid (NFA), which uncovers a mechanism of inhibition by competing with anion binding and impeding the structural changes necessary for anion exchange. These results reveal directions for understanding the mechanisms of anion selectivity and exchange and their regulations by the STAS domain. This work also establishes a foundation for analyzing the pathophysiology of mutations associated with Pendred syndrome.


Subject(s)
Hearing Loss, Sensorineural , Humans , Bicarbonates , Chlorides , Cryoelectron Microscopy , Halogens , Swine , Animals
15.
Adv Mater ; 36(6): e2307726, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37775103

ABSTRACT

Diseases in pregnancy endanger millions of fetuses worldwide every year. The onset of these diseases can be early warned by the dynamic abnormalities of biochemicals in amniotic fluid, thus requiring real-time monitoring. However, when continuously penetrated by detection devices, the amnion is prone to loss of robustness and rupture, which is difficult to regenerate. Here, an interface-stabilized fiber sensor is presented for real-time monitoring of biochemical dynamics in amniotic fluid during pregnancy. The sensor is seamlessly integrated into the amnion through tissue adhesion, amniotic regeneration, and uniform stress distribution, posing no risk to the amniotic fluid environment. The sensor demonstrates a response performance of less than 0.3% fluctuation under complex dynamic conditions and an accuracy of more than 98% from the second to the third trimester. By applying it to early warning of diseases such as intrauterine hypoxia, intrauterine infection, and fetal growth restriction, fetal survival increases to 95% with timely intervention.


Subject(s)
Amnion , Amniotic Fluid , Pregnancy , Female , Humans
16.
Medicine (Baltimore) ; 102(48): e36345, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38050266

ABSTRACT

BACKGROUND: Previous epidemiological studies have shown inconsistent results regarding the relation between the risk of asthma in offspring and parental occupational exposure. Therefore, we conducted a comprehensive and systematic collection of currently available epidemiological data to quantify the correlation between the 2. METHODS: Related studies published before March 2023 were identified through searches of the Cochrane Library, Embase, PubMed, and Web of Science databases. The quality of included studies was assessed using the Newcastle-Ottawa Scale, while pooled odds ratios (ORs) with 95% confidence intervals (CIs) were computed using fixed-effect or random-effects models. RESULTS: This systematic review included 10 cohort studies, with a total of 89,571 parent-child pairs included in the quantitative analysis. The results exhibited a substantial association between parental occupational exposure to allergens (OR = 1.11; 95% CI: 1.00, 1.23; P = .051) and irritants (OR = 1.19; 95% CI: 1.07, 1.32; P = .001) and an increased risk of asthma in offspring. This association was also observed in the analysis of wheezing (OR = 1.22; 95% CI: 1.11, 1.35; P < .001 and OR = 1.19; 95% CI: 1.08, 1.32; P = .001). Subgroup analysis demonstrated that maternal occupational exposure to allergens (OR = 1.07; 95% CI: 1.02, 1.12; P = .008) and irritants (OR = 1.13; 95% CI: 1.05, 1.21; P = .001) significantly increased the risk of childhood asthma. Furthermore, parental postnatal occupational exposure to allergens (OR = 1.26; 95% CI: 1.10, 1.46; P = .001) and irritants (OR = 1.26; 95% CI: 1.06, 1.49; P = .009) had a more pronounced impact on childhood asthma. Higher levels of exposure (OR = 1.26; 95% CI: 1.10, 1.46; P = .001 and OR = 1.30; 95% CI: 1.16, 1.47; P < .001) were recognized as significant risk factors for childhood asthma. CONCLUSION: Parental occupational exposure to allergens and irritants increases the risk of asthma and wheezing in offspring, with maternal exposure, postnatal exposure, and high-dose exposure being the primary risk factors for childhood asthma.


Subject(s)
Asthma , Occupational Exposure , Female , Humans , Respiratory Sounds/etiology , Irritants , Occupational Exposure/adverse effects , Asthma/etiology , Asthma/complications , Parents , Allergens/adverse effects
17.
Sci Immunol ; 8(89): eadi9066, 2023 11 10.
Article in English | MEDLINE | ID: mdl-37948511

ABSTRACT

How CD4+ lineage gene expression is initiated in differentiating thymocytes remains poorly understood. Here, we show that the paralog transcription factors Zfp281 and Zfp148 control both this process and cytokine expression by T helper cell type 2 (TH2) effector cells. Genetic, single-cell, and spatial transcriptomic analyses showed that these factors promote the intrathymic CD4+ T cell differentiation of class II major histocompatibility complex (MHC II)-restricted thymocytes, including expression of the CD4+ lineage-committing factor Thpok. In peripheral T cells, Zfp281 and Zfp148 promoted chromatin opening at and expression of TH2 cytokine genes but not of the TH2 lineage-determining transcription factor Gata3. We found that Zfp281 interacts with Gata3 and is recruited to Gata3 genomic binding sites at loci encoding Thpok and TH2 cytokines. Thus, Zfp148 and Zfp281 collaborate with Gata3 to promote CD4+ T cell development and TH2 cell responses.


Subject(s)
CD4-Positive T-Lymphocytes , Transcription Factors , Animals , Mice , CD4-Positive T-Lymphocytes/metabolism , Cell Differentiation/genetics , Cytokines/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
18.
Elife ; 122023 Nov 20.
Article in English | MEDLINE | ID: mdl-37983176

ABSTRACT

Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether FAD, which relays electrons from NADPH in OxRD to heme in TMD, remains constantly bound to the STEAPs. We found that FAD reduced by STEAP2 can be utilized by STEAP1, suggesting that FAD is diffusible rather than staying bound to STEAP2. We determined the structure of human STEAP2 in complex with NADP+ and FAD to an overall resolution of 3.2 Å by cryo-electron microscopy and found that the two cofactors bind STEAP2 similarly as in STEAP4, suggesting that a diffusible FAD is a general feature of the electron transfer mechanism in the STEAPs. We also demonstrated that STEAP2 reduces ferric nitrilotriacetic acid (Fe3+-NTA) significantly slower than STEAP1 and proposed that the slower reduction is due to the poor Fe3+-NTA binding to the highly flexible extracellular region in STEAP2. These results establish a solid foundation for understanding the function and mechanisms of the STEAPs.


Subject(s)
Electrons , Prostate , Male , Humans , NADP/metabolism , Cryoelectron Microscopy , Prostate/metabolism , Oxidoreductases/metabolism , Heme/metabolism , Antigens, Neoplasm
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1366-1371, 2023.
Article in Chinese | MEDLINE | ID: mdl-37846686

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and chromosome abnormalities, and further analyze the correlation between the degree of chromosome abnormality and prognosis. METHODS: The clinical data of 88 patients diagnosed with DLBCL with bone marrow involvement and complete chromosomal findings in Shanxi Province Cancer Hospital were retrospectively analyzed. The χ2 test was used to analyze their clinical characteristics, and the Kaplan-Meier method was used in PFS and OS, and log-rank method in comparison. RESULTS: Chromosome abnormalities were detected in 31 of the 88 patients(35.2%), 15 of whom had complex karyotype(17.0%). The positive rate of BCL-2, BCL-6, C-MYC and Ki-67≥80% was high in patients with complex karyotype, and most of them are double expressor lymphoma. Survival analysis showed that patients with complex karyotype of DLBCL had poorer PFS and OS compared to those with normal karyotype and 1-2 chromosomal abnormalities. CONCLUSION: In DLBCL patients with bone marrow involvement and chromosome abnormalities, patients with complex karyotype have a shorter survival time.

20.
BMC Anesthesiol ; 23(1): 327, 2023 10 02.
Article in English | MEDLINE | ID: mdl-37784079

ABSTRACT

BACKGROUND AND OBJECTIVES: Dexmedetomidine (DEX) is widely used in clinical sedation which has little effect on cardiopulmonary inhibition, however the mechanism remains to be elucidated. The basal forebrain (BF) is a key nucleus that controls sleep-wake cycle. The horizontal limbs of diagonal bundle (HDB) is one subregions of the BF. The purpose of this study was to examine whether the possible mechanism of DEX is through the α2 adrenergic receptor of BF (HDB). METHODS: In this study, we investigated the effects of DEX on the BF (HDB) by using whole cell patch clamp recordings. The threshold stimulus intensity, the inter-spike-intervals (ISIs) and the frequency of action potential firing in the BF (HDB) neurons were recorded by application of DEX (2 µM) and co-application of a α2 adrenergic receptor antagonist phentolamine (PHEN) (10 µM). RESULTS: DEX (2 µM) increased the threshold stimulus intensity, inhibited the frequency of action potential firing and enlarged the inter-spike-interval (ISI) in the BF (HDB) neurons. These effects were reversed by co-application of PHEN (10 µM). CONCLUSION: Taken together, our findings revealed DEX decreased the discharge activity of BF (HDB) neuron via α2 adrenergic receptors.


Subject(s)
Dexmedetomidine , Mice , Animals , Dexmedetomidine/pharmacology , Receptors, Adrenergic, alpha-2 , Signal Transduction , Neurons , Adrenergic alpha-2 Receptor Agonists/pharmacology
SELECTION OF CITATIONS
SEARCH DETAIL
...